BOARD OF DIRECTORS MEETING
December 15, 2016
CSIS Building WASHINGTON, D.C.
PERSONALIZED MEDICINE COALITION BOARD MEETING
December 15, 2016 10:00 a.m. to 2:00 p.m.
CSIS Building Washington, D.C. 9th Floor Turret Room
Agenda
Chairman’s Report
1. Approval of May 25, 2016 Minutes 2. Nominations Committee
President’s Report
3. 2016 Progress Report 4. Plans for 2017 5. Finance and Budget 6. Membership 7. Public Policy 8. Science Policy 9. Communications
New Business
December 2016 Board Meeting Table of Contents
Agenda 1. Minutes – May 25, 2016 2. Nominations • Current Board Members • Board Composition by Category • Board of Directors Duties • Bylaws 3. Progress Report • 2016 Progress Report • Conference Program (back pocket) 4. Plans for 2017 • Strategic Plan for 2017 • Clinical and Economic Value of Next-Generation Sequencing • The Personalized Medicine Education Initiative • International Comparative Landscape Analysis • Evidence for Coverage and Payment of Personalized Medicine Diagnostics • Personalized Medicine in Value Assessment Frameworks • Turning the Tide Against Cancer 2017 Conference Prospectus • CRD Proposal: Public Policy • Jen Leib Biography • PMC Vice President, Public Policy: Job Description • Kayla Smith Resume 5. Finance and Budget • 2017 Budget • Historical Budget • 2016 Sponsorships • Friends of PMC • Cash and Investments • Chart: Revenues & Expenses • Chart: Membership & Financial Performance • Chart: Cumulative Net Assets • Investment Detail 6. Membership Status • Chart: PMC Membership Numbers • Dues Schedule for Members and Sponsors • Organizations that have withdrawn from PMC since 2007 • Chart: Analysis of 2015 and 2016 Membership Non-Renewal by Reason • 2016 and 2017 New Members • Target List for 2017 Membership • List of PMC Members • Chart: PMC Membership Numbers by Category • 2016 Sponsorships 7. Public Policy • Letter to CMS on 2016 Preliminary Gapfill Payment Determinations • 2016 BIO International Convention: Personalized Medicine and Diagnostics Program Track • Letter to ICER on Non-Small Cell Lung Cancer Scoping Document • Letter to ICER on Proposed Process Improvements to Value Assessment Framework • Letter to FDA on Codevelopment • “Where We Agree When It Comes to Regulating Laboratory-Developed Diagnostics” in Personalized Medicine in Oncology 8. Science Policy • “Strategies for Integrating Personalized Medicine into Health Care Practice” (Manuscript) • Letter to FDA on Standards for Regulatory Oversight of NGS Oversight and the Use of Public Genetic Variant Databases to Support Clinical Validity for NGS-based IVDs • Policy Meeting Agenda: Envisioning the Value of Personalized Medicine (June 21, 2016) • Policy Meeting Agenda: An Update on the Precision Medicine Initiative (October 11, 2016) • Policy Meeting Agenda: PCORI & FDA in 2017 (December 7, 2016) • PMC Blog: “An Infrastructure for Innovation: How the 21st Cenury Cures Bill Could Establish a More Favorable Landscape for Personalized Medicine in 2017” • The Personalized Medicine Report 9. Communications • Impact Report • 2016 Press Releases 1. PMC to Recognize Raju Kucherlapati With 12th Annual Leadership in Personalized Medicine Award (June 29, 2016) 2. PMC Commends ICER for Extending Public Comment Period for Scope of Work in Non-Small Cell Lung Cancer (Jul 1, 2016) 3. Coalition Applauds Progress on Precision Medicine Initiative, Encourages Additional Efforts in Regulation, Reimbursement (July 7, 2016) 4. PMC Commends ‘Moonshot’ Panel for Recognizing Personalized Medicine’s Importance in Research Recommendations, Encourages Complementary Efforts From Policymakers (September 7, 2016) • 2016 Member Updates o Example • 2016 Blogs 1. Of Moonshots and Precision Medicine: Why the Time is Ripe for a National Cancer Moonshot (Kenna Shaw, Ph.D.: May 19, 2016) 2. Informed Perspectives: A Preview of the Personalized Medicine & Diagnostics Track at the 2016 BIO International Convention (Chris Wells: May 31, 2016) 3. ICER & Personalized Medicine: Time to Engage (Amy Miller, Ph.D.: June 29, 2016) 4. What ICER is Missing (Amy Miller: September 1, 2016) 5. Think the Diagnostics Community Doesn’t Agree on Anything When It Comes to LDT Regulation? Think Again. (Amy Miller: September 20, 2016) 6. Beyond the Barriers: Deconstructing the Regulatory and Reimbursement Hurdles for Companion Diagnostics (Alessandra Cesano, M.D., Ph.D.: October 3, 2016) 7. Can We Assess the Value of Personalized Medicine in Treating Cancer? (Dan Leonard, M.A.: October 19, 2016) 8. It’s Time to Protect Patient Care and Rethink the Way We Define and Assess Clinical Utility in Molecular Diagnostics (Elaine Lyon, Ph.D.: November 4, 2016) 9. A Chancellor’s Tale: Transforming Academic Medicine (Ralph Snyderman, M.D.: November 8, 2016) 10. An Infrastructure for Innovation: How the 21st Century Cures Bill Established a More Favorable Landscape for Personalized Medicine in 2017 (Daryl Pritchard, Ph.D.: December 6, 2016) 11. Advancing the Promise of Personalized Medicine With Liquid Biopsies and Analysis of ctDNA (John Beeler, Ph.D.: December 8, 2016) • Twitter Engagement: @permedcoalition • 2016 Speaking Engagements • 2016 Staff Publications • 2016 Earned Media
2016 Impact Report (spiral-bound) • 2016 Impact Report • List of Staff Publications • List of 2016 Media Mentions • Full Text of Selected Publications & Placements
Supplements • Board Directory (front pocket)
Finalized Publications (back pocket) • Personalized Medicine in Brief • 12th Annual Personalized Medicine Conference Program
1. Minutes – May 25, 2016 MINUTES OF THE MEETING OF THE PERSONALIZED MEDICINE COALITION BOARD OF DIRECTORS OF MAY 25, 2016
MEMBERS PRESENT: Edward Abrahams (PMC), President; Amy Abernethy (Flatiron Health), Secretary; Donna Cryer (Global Liver Institute); William Dalton (M2Gen), Chair; Neil de Crescenzo (Change Healthcare); Stephen Eck (Astellas), Vice Chair; Michael Kolodziej (Aetna); Howard McLeod (Moffitt); Michael Pellini (Foundation Medicine); Kim Popovits (Genomic Health); Lori Reilly (PhRMA); Hakan Sakul (Pfizer); Jay Wohlgemuth (Quest)
OTHERS PRESENT: Amy M. Miller (PMC Executive Vice President); Daryl Pritchard (PMC Vice President, Science Policy); Faswilla Sampson (PMC Director, Operations & Secretary to the Board); Christopher Wells (PMC Director, Communications); Mary Bordoni (PMC Director, Membership & Development); David Davenport (PMC Office Administrator); Marina Polyakova (Rogers & Company Principal)
A meeting of the Personalized Medicine Coalition (PMC) Board of Directors was held at the National Press Club in Washington, D.C. A quorum being present, Board Chair William Dalton called the meeting to order at 8:25 a.m.
Chairman’s Report
Dalton asked for and received approval of the Board meeting minutes of November 21, 2015.
Finance and Budget
Abrahams introduced Marina Polyakova, Principal of Rogers and Company, PMC’s outside auditor, to explain its report for 2015 (Attachment 1). She noted that PMC is financially sound, with over eight months’ cash reserves and $1.35 million in unrestricted net assets. She informed the Board that while PMC lost about $42,000 in its investment portfolio in 2015 as a result of market fluctuation, the paper loss had not had a significant impact and was in keeping with that experienced by many non- profits during 2015. She also said that PMC’s financial statements were “clean.” Her team, she said, experienced no difficulty when auditing them and confirmed that proper internal controls are in place, thanks to PMC’s careful financial management.
Following the presentation of the audit, Dalton asked for and received approval of the IRS Form 990 for 2015 (Attachment 2) that all non-profits are required to file.
1 Leadership Award
While there were many strong candidates, the Board identified two finalists for the 12th Annual Award for Leadership in Personalized Medicine: Raju Kucherlapati of Harvard Medical School and Ellen Sigal of Friends of Cancer Research. Kucherlapati received exalted praise and expressions of support from the Board for his work in personalized medicine, as did Ellen Sigal for her forceful leadership.
In a subsequent discussion, Amy Abernethy summarized the factors that, in her view, the Board should consider when selecting the winner of the award: leadership, timing, and purpose. Donna Cryer suggested that the Board also consider who best represents PMC’s brand and mission. Jay Wohlgemuth said Kucherlapati has been the premier agent working in personalized medicine across the three areas PMC focuses on: science, business, and policy.
A few members raised the concern about various recipients’ availability to accept the award at the conference. Kim Popovits encouraged the Board to consider other means of allowing recipients to accept the award (e.g. video acceptance) and not simply select recipients because they can be present at the conference.
The Board unanimously selected Raju Kucherlapati as the recipient of the 2016 Leadership Award.
Nominating Committee
Noting their commitment to personalized medicine and to PMC, Dalton asked that the current slate of officers be re-elected and serve until the end of the year. They are Bill Dalton, Chair; Stephen Eck, Vice Chair; Stafford O’Kelly, Treasurer; and Amy Abernethy, Secretary.
Regarding the growth of the Board, Dalton indicated that the Coalition should focus on securing additional representation from insurance companies, and asked Michael Kolodziej how the Coalition can best meet the needs of insurers. Kolodziej responded that asking for payers to assume a Board seat or become dues-paying members is unrealistic in his opinion. Instead, the first strategy, he said should be to form an advisory committee to solicit advice.
Wohlgemuth said that getting payers to engage in a workshop around payment for personalized medicine might be a smarter idea. Donna Cryer proposed an even more informal approach, suggesting that the Coalition simply start a conversation with payers without a predetermined agenda.
2 Michael Pellini mentioned four stakeholders he believes are underrepresented on the Board: insurance companies, patient advocates, academic medical centers, and representatives from the policy community.
Abrahams asked the Board to help identify new Board members for consideration within the next six months, noting that Board members have a pivotal role to play in providing leadership and helping underwrite the organization’s efforts to show how personalized medicine can benefit the entire health care system. (See Attachment 3 for the current Board composition.)
Popovits noted the need to be strategic in Board outreach, and Kolodziej offered to help put PMC in contact with payers and health systems.
President’s Report
Introduction
Abrahams thanked the Board for its leadership, and said that the Coalition was making progress toward meeting the objectives outlined in its strategic plan for 2016 (Attachment 4). Those objectives include highlighting the issues, facilitating the development of best strategies to integrate personalized medicine into health care, promoting policies to encourage investment, promoting regulatory reforms, defining how personalized medicine can be enhanced through reimbursement, and supporting increased public funding for research.
He also said PMC still has a lot of educational work to do about the principles and purpose of personalized medicine, and needs more evidence that it works not only for patients but also for the health system at large. In the current cost-cutting environment, he noted, there has been too little consideration of how across-the- board payment decisions, for example, will impact individual patients, presenting a challenge both to the Coalition and to the future of medicine. PMC’s special projects, he said, were in part designed to meet that need.
Abrahams reviewed PMC’s finances, noting, as had the auditor, that they are sound and that PMC should have another successful year if current trends associated with the conference and the Coalition’s other activities continue.
According to the budget (Attachment 5), as of April 29, 2016, PMC has collected almost $1 million in membership revenue, or about 60 percent of its $1.6 million goal in keeping with trends from previous years. Abrahams also noted that as of April 29, PMC’s expenses equal about one third of its total budget of $2.3 million. Abrahams
3 also said that PMC would hire an additional staff member to help with membership and development, which, while adding to the payroll, represents a strategic decision to increase outreach and therefore revenues. Lastly, not including cash currently in its checking account, PMC’s investment portfolio totals $1.3 million. The year-to-date return on PMC’s two conservatively invested mutual funds, Abrahams said, is 3.84 percent, or about $35,000.
Abernethy cautioned the Coalition against under-investing in programs, given that it has eight and a half months operating costs in spending reserves.
Membership
In her report to the Board, Mary Bordoni noted that, as of May 23, PMC had collected just over $1 million, or 63 percent of PMC’s anticipated membership revenue of $1.62 million. This, she said, was similar to previous years, when payment of yearly membership dues from some members came slowly.
Regarding sponsorship, Bordoni stated, PMC is almost halfway to its goal of $500,000, having invoiced $209,000. The Coalition is optimistic, she said, that it will reach its goal through fundraising efforts for the annual conference at Harvard Medical School, today’s State of Personalized Medicine Luncheon, PMC’s Education Initiative, the NGS value project, the International Landscape Analysis, and unrestricted grants.
Bordoni thanked generous Board members who have already committed funds to these initiatives. Through continued outreach and by demonstrating and conveying its value, she said, PMC will be able to attract new members as well as engage and retain current members.
Hakan Sakul asked what Board members can do to help with membership outreach and suggested PMC create a template that Board members can use when conducting outreach for the Coalition. Pellini followed up by asking if there were tailored messages to specific audiences for outreach. Bordoni agreed a template would facilitate the Board’s ask when reaching out to potential new members. She also noted that since there are specific messages for particular audiences, the template could be customized for selected groups.
Popovits pointed out the dues structure could also be revisited. Pellini noted that when considering possible dues increases it might also be useful to put in place an increase in the level of outreach and engagement with members. Popovits explained that the Coalition might consider charging for access to certain material, which is
4 currently available at no charge. Lori Reilly added that it is important to explain to potential members the value of membership.
Initiatives
12th Annual Personalized Medicine Conference at Harvard Medical School
Abrahams said that by assuming responsibility for the annual personalized medicine conference, PMC had seized an opportunity to shape the agenda for personalized medicine, something that will differentiate its conference from a crowded field. Stephen Eck noted that the conference focuses on the critical subjects, while Donna Cryer added that its wide-ranging program is excellent.
Sakul said that it was essential for Board members to sponsor the conference to help ensure its success, noting that Pfizer had already committed funds.
Click here to view the conference website.
Education Initiative
Chris Wells explained the Education Initiative and reviewed the website that will host it. Noting that it will become a “one-stop shop” for understanding personalized medicine, he stated that the Education Initiative addresses the lack of knowledge about the subject and raises awareness that personalized medicine can improve patient outcomes and benefit the health system. He remarked that additional funds would allow PMC to accelerate progress in building the website and refine its visual impact. The current site, Wells said, demonstrates the initiative’s potential.
Howard McLeod encouraged PMC to send communication about the site to medical schools, and said that downloadable PowerPoint presentations would also be useful. Abernethy reminded the Coalition that personalized medicine is larger than “genomic medicine,” and encouraged PMC to keep that in mind when building the resource. Sakul noted that it might also be worthwhile to define concepts and get agreement before disseminating widely. Popovits and Reilly raised the issue of member value again, suggesting that PMC might develop a separate members-only site to access and download materials.
Click here to view the online Education Initiative.
5 Health Economic Value of Precision Cancer Care
Daryl Pritchard discussed PMC’s project aimed at demonstrating the clinical and economic value of next-generation sequencing. Pellini and Wohlgemuth, co-leaders of the effort, stated that the concept has evolved since its inception to include a defined objective: to identify the clinical and economic value of NGS diagnostic tests in solid tumor cancer care through a model applied to a single condition at first, either NSCLC or melanoma. The model can then, Wohlgemuth explained, be expanded to other forms of cancer more broadly. Pellini noted that the current project timeline is 18 months, but suggested that it would be revised downward to have a greater impact. Wohlgemuth also noted that the steering committee includes an engaged group of stakeholders committed to the study’s success, adding that, in his view, the payer community should be interested in the findings. The next step, he said, is to finalize the budget and to confirm additional financial commitments from others to match Quest’s grant.
Dalton asked what could realistically be expected after six months. Wohlgemuth and Pellini said they believe a model can be developed and applied to a single illustrative case in a way that will influence thinking among payers. Expansion of the analysis to other indications could follow. The key, they said, would be getting appropriate data sets to run through the model. Abernethy asked that the project steering committee reach out to her regarding using FlatIron data sets. Wohlgemuth noted that the project steering committee is working with the principal investigator to finalize the proposal.
Public Policy
Amy Miller noted that PMC’s unique position as a multi-stakeholder education and advocacy organization allows it to explain how personalized medicine can benefit both patients and the health system and identify the policy levers that can make that happen.
Like last year, Miller said, in 2016 PMC is seeing personalized medicine move to the center of discussions about health care as targeted treatments have become a more sizeable part of new treatments coming to the market. She reiterated the need for the health care environment to align its policies to encourage further development and adoption of those products.
Miller mentioned the conflicting points of view among the White House, FDA, and CMS regarding personalized medicine. For example, when the White House announced its Cancer “Moonshot” initiative, PMC pointed out that CMS, a very
6 powerful agent in determining whether or not innovative products are adopted, was not even invited to discussions about it. The Coalition strongly suggested that CMS be added to the list. PMC’s comment, Miller said, was picked up by STAT News and has now become a regular criticism of the effort.
She also mentioned that PMC’s work on public policy has attracted attention from organizations like AMA, which asked PMC to try to bridge the differences of opinion among stakeholders regarding regulating laboratory-developed tests, culminating in a meeting with FDA. Moving forward, she said, PMC intends to assist the leaders of the Precision Medicine and Moonshot Initiatives as these efforts transition to the new administration.
Communications
Wells reported that PMC’s aggressive, proactive strategy to define the field has paid off in 2016 in both anticipated and unanticipated ways for the Coalition.
By capitalizing on its various work products and excellent relationships with editorial staffs, for example, Wells noted that PMC has published more than 10 articles in personalized medicine journals so far this year. These articles include a cover story in The Journal of Precision Medicine that illustrates the pharmaceutical industry’s commitment to the personalized medicine field. The article, which Abrahams wrote with Stephen Eck, provides additional exposure for the field and for the Coalition.
Wells also noted that PMC is on track to implement its planned communications agenda. PMC’s blog, Education & Advocacy, now features guest bloggers that include trade association CEOs and prominent researchers, and is recognized as an impactful place to publish. The blog has also served as a source for stories in Bloomberg BNA and The Gray Sheet. PMC’s work, he said, has generated nearly 50 media citations so far this year. Wells also said that Personalized Medicine in Brief, PMC’s redesigned newsletter, represents an additional outlet for the Coalition, and has also attracted additional revenue for PMC through advertising.
Reilly suggested and offered to help put together a roundtable conversation on personalized medicine with key health care reporters. She also suggested that PMC expand its communications network. To help facilitate that, Wohlgemuth agreed to introduce Wells to communications colleagues at Quest, and encouraged other Board members to do the same. Cryer encouraged Wells to use PMC’s existing materials to develop a weekly/monthly communications schedule for Tweets.
7 Conclusion
The Board meeting adjourned at approximately 12:03 p.m.
8
2. Nominations
PMC Board of Directors Current Members
November 24, 2003, Brian Munroe
June 3, 2010, Stafford O’Kelly*
November 16, 2010, Stephen Eck*
February 3, 2011, William Dalton* and Jared Schwartz*
June 9, 2011, Amy Abernethy*
May 8, 2012, Neil de Crescenzo*
July 18, 2012, Paul Billings*, Donna Cryer*, Tim Garnett* and Mike Vasconcelles*
November 5, 2013, Steven Averbuch
March 13, 2014, Jay Wohlgemuth
November 11, 2014, Michael Pellini and Howard McLeod
May 14, 2015, Kimberly Popovits and Hakan Sakul
August 8, 2016, Bonnie Addario, William Chin and Susan McClure
October 5, 2016, Brad Gray, Peter Maag and Michael Sherman
* Re-elected
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Nominations | p. 2 Board Composition by Category
Large Biotech/Pharmaceutical Companies (4) Steven Averbuch (Bristol-Myers Squibb) Stephen Eck (Astellas Pharma Global Development) Tim Garnett (Eli Lilly and Company) Hakan Sakul (Pfizer, Inc.)
Research & Education (3) William Dalton (M2Gen) Susan McClure (Genome magazine) Howard McLeod (Moffitt Cancer Center)
Diagnostic Companies (5) Paul Billings (Biological Dynamics) Brad Gray (NanoString) Peter Maag (CareDx) Michael Pellini (Foundation Medicine) Kim Popovits (Genomic Health)
Emerging Biotech/Pharmaceutical Companies (2) Brian Munroe (Endo) Mike Vasconcelles (Unum Therapeutics)
IT/Informatics Companies (2) Amy Abernethy (Flatiron Health) Neil de Crescenzo (Change Healthcare, Inc.)
Health Insurance Companies (1) Michael Sherman (Harvard Pilgrim HealthCare)
Industry & Trade Associations (1) William Chin (PhRMA)
Patient Advocacy Groups (2) Bonnie Addario (Bonnie J. Addario Lung Cancer Foundation) Donna Cryer (Global Liver Institute)
Research Tool Companies (0)
Clinical Laboratory Testing Services (1) Jay Wohlgemuth (Quest)
Total: 21
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Personalized Medicine Coalition (PMC)
Board of Directors Duties
Position Summary
As a member of the PMC Board of Directors, I assume responsibility for ensuring PMC’s long- term financial stability and integrity. Specifically, I agree to the following:
General Expectations and Responsibilities
SERVICE • To prepare for, and attend in their entirety, all Board meetings (missing no more than one in any given year). • To serve in leadership positions and accept committee assignments willingly and enthusiastically when asked. • To bring a sense of humor to the Board’s deliberations. • To obey the law of the governance documents and apply a duty of care, and loyalty to the organization. • To serve until the expiration of my term or until a successor is chosen and qualified. • To serve no more than two consecutive three-year terms.
POLICY • To participate in the development and establishment of policies through which the work of the organization is accomplished. • To suggest appropriate policy-related agenda items for meetings and ask timely and substantive questions, while supporting the majority decision on matters decided by the Board. • Preferably, to bring the experience of service on other successful Boards and with growing organizations.
PLANNING • To help ensure effective organizational planning by reviewing, critiquing, and approving annual budgets and workplans, as well as long-range plans. • To be knowledgeable about the environment in which the organization functions. • To assist the organization in interpreting the community it serves by following trends in our field of interest. • To identify changing stakeholder interests and build stakeholder investment.
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FINANCES • To help ensure the organization’s long-term financial stability and integrity. • To adopt an annual budget for the organization. • To ensure that annual audits of the organization’s finances are conducted. • To read and understand the organization’s financial statements and otherwise assist the Board to fulfill its fiduciary responsibility.
DEVELOPMENT • To contribute to ensuring the adequacy of resources to meet effectively the organization's current needs and its long-term financial solvency. • To identify and cultivate diverse sources of potential funding and other needed resources. • To encourage and support management to take calculated risks and apply appropriate controls when investing the organization’s assets wisely in development activities. • To respect that responsibility for containing costs must be balanced with adequate long-term commitment to revenue enhancing development efforts. • To participate actively in fundraising events undertaken by the organization and such activities approved by the Board for the purpose of enhancing the organization's income base.
PROGRAMMING • To participate in determining among competing priorities the organization's programs and services and monitoring them for quality and cost-effectiveness. • To contribute to ensuring that current and proposed programs and services are consistent with the organization's stated mission, goals, and financial means. • To encourage participation in programs and use of services. • To set program priorities, provide fiscal oversight, and ensure that adequate resources are available and directed to priorities. • To seek opportunities for collaborative activities with my own organization.
EVALUATION • To participate in appointing, supporting, and monitoring the performance of the chief staff officer. • To offer counsel to the chief staff officer as appropriate. • To empower the chief staff officer to provide necessary leadership direction.
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INTEGRITY • To maintain independence and objectivity and serve with a sense of ethics and personal integrity. • To avoid even the appearance of a personal or institutional conflict of interest that might embarrass or cause legal liability for the Board or the organization. • To disclose any possible conflicts to the Board of Directors in a timely manner. • To protect and maintain the confidentiality of Board of Directors actions and organization documents, as appropriate.
RECRUITMENT • To suggest possible nominees to the Board who are individuals of achievement and distinction and can make significant contributions to the work of the Board and the organization’s progress. • To assist in efforts to identify and recruit new members. • To suggest possible nominees for Board officer positions. • To participate in Board elections.
SELF- • To participate in the Board's periodic assessment of its own ASSESSMENT performance and recommend improvements in such areas as composition, organization, tenure, retention, and responsibilities.
SIGNATURE OF ACKNOWLEDGEMENT ______
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AMENDED AND RESTATED BYLAWS
OF
PERSONALIZED MEDICINE COALITION (THE "CORPORATION")
(formed under the District of Columbia Nonprofit Corporation Act)
ARTICLE I. OFFICES AND REGISTERED AGENT
Section 1.1. Location. The principal office of the Corporation shall be located within or without the District of Columbia, at such place as the Board of Directors shall from time to time designate. The Corporation may maintain additional offices at such other places as the Board of Directors may designate. The Corporation shall have and maintain within the District of Columbia a registered office at such place as may be designated by the Board of Directors.
ARTICLE II. MEMBERS
Section 2.1. Members: Classes and Qualifications. The Board of Directors shall determine and set forth in separate documents the qualifications, annual dues, terms of membership, and other conditions of each class of member.
Section 2.2. No Voting Rights. Unless otherwise specified by the Board of Directors, no members shall have any voting rights, but institutional members may be invited to have a representative serve on committees and have such other privileges as the Board of Directors may determine from time to time.
Section 2.3. Removal. Any member may be removed from membership by a majority vote of the Board of Directors only for cause, including but not limited to failure to adhere to the Articles of Incorporation, the Bylaws, or other rules or regulations issued by the Board of Directors or externals laws, or other conduct that the Board of Directors reasonably determines is inconsistent with the mission and purposes of the Corporation. In addition, membership shall automatically be subject to termination for failure to pay dues.
ARTICLE III. DIRECTORS
Section 3.1. Power of the Board and Qualification of Directors. The business, property and affairs of the Corporation shall be managed by or under the direction of its Board of Directors.
Section 3.2. Number of Directors. The number of directors constituting the entire Board of Directors shall be not less than ten (10). The precise number of directorships shall be the number fixed by resolution of the directors.
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Nominations | p. 9 Section 3.3. Election and Term of Directors. The initial Board of Directors shall be comprised of those directors named in the Articles of Incorporation. Thereafter, the officers of the Corporation shall serve as ex officio directors with vote and the remaining directors shall be elected by an affirmative vote of a majority of the directors then in office. Only persons who are employed by institutional members may serve as directors. Each elected director shall continue in office for a term of three (3) years or until his or her successor is elected; provided that any director who ceases to be employed by the institutional member with which the director was affiliated when initially elected must stand for re-election as a director within six (6) months of such change of affiliation. The tenure of the incumbent members of the Board of Directors shall not be affected by an increase or decrease in the number of directors. Each elected director may serve up to two (2) three (3)-year terms, subject to the change of affiliation provisions set forth in this subsection 3.3. The terms of elected directors shall be staggered so that each year the terms of approximately one-third of the elected directors shall expire, and new directors will be elected or re-elected to fill those seats.
Section 3.4. Vacancies and Newly-Created Directorships. Vacancies and newly- created directorships, resulting from any increase in the authorized number of directors, may be filled by a majority vote of a quorum of the directors then in office. A director elected to fill a vacancy shall be elected to serve until the next meeting at which directors are elected and until such director's successor is elected.
Section 3.5. Resignations. Any director may resign at any time upon notice given in writing or by electronic transmission to the Chair of the Corporation. Such resignation shall take effect at the time specified therein, and unless otherwise specified therein no acceptance of such resignation shall be necessary to make it effective.
Section 3.6. Removal of Directors. Any one or more of the elected directors may be removed with or without cause at any time by a majority vote of the Board of Directors at any meeting called expressly for that purpose, provided written notice of such removal is given to any director so removed.
Section 3.7. Quorum of Directors, Action of the Board of Directors and Adjournment. Unless a greater proportion is required by law or by the Articles of Incorporation, a majority of the entire Board of Directors then in office shall constitute a quorum for the transaction of business, and the act of a numerical majority of the directors present at a meeting at which a quorum is present shall be the act of the Board of Directors, unless the presence of or act of a greater number of directors is specifically required by these Bylaws, the Corporation's Articles of Incorporation, or the laws of the District of Columbia. If a quorum shall not be present at any meeting of the Board of directors, a majority of the directors present at such meeting may adjourn the meeting from time to time, without notice other than announcement at the meeting, until a quorum shall be present.
Section 3.8. Meetings and Notices. Annual meetings of the Board of Directors shall be held each year at such time and place as shall be fixed by the Board of Directors, for the election of officers and directors and for the transaction of such other business as may properly come before the meeting. Notice of the annual meeting shall be in writing and shall be sent by regular
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Nominations | p. 10 mail, express mail, hand delivery, facsimile or electronic mail to all directors at least ten (10) days before the annual meeting.
(a) Regular meetings of the Board shall be held at such times as may be fixed by the Board. Special meetings of the Board may be held at any time whenever called by the Chair of the Board, the President or any two directors. At least two (2) days' written or oral notice stating the time, place and purpose of special meetings shall be given to each director. No business other than that stated by the notice of special meeting may be conducted.
(b) Meetings of the Board of Directors may be held at such places within or without the District of Columbia as may be fixed by the Board of Directors for annual or regular meetings and in the notice of meeting for special meetings.
Section 3.9. Meetings by Conference Telephone. A director may participate in a meeting through the use of any means of communication enabling all directors participating in the meeting to hear one another, and participation in a meeting shall constitute presence in person at such meeting.
Section 3.10. Waiver of Notice. A written waiver signed at any time by a director entitled to notice shall be the equivalent to the giving of notice. The attendance of any director at a meeting without protesting at the beginning of the meeting or promptly upon his arrival thereat the lack of proper notice shall be deemed to be a waiver by such director of notice of the meeting.
Section 3.11. Action Without a Meeting. Any action that may be taken at a meeting may be taken without a meeting if a consent in writing, setting forth the action so taken, or to be taken, shall be signed by all of the directors entitled to vote with respect to the subject matter of such meeting. Such consent shall be filed with the minutes. Any written document (including facsimile, e-mail, or other electronic transmission) shall constitute writing for the purposes of this Section.
Section 3.12. Minutes. The Secretary shall record the minutes of each meeting of the Board of Directors and upon adoption by the Board of Directors shall retain such minutes with the permanent records of the Corporation.
Section 3.13. Compensation. The Corporation shall not pay any compensation to directors for services rendered to the Corporation, except for the President, and except that reasonable allowance may be paid to a director for expenses actually incurred in the performance of his duties to the Corporation.
ARTICLE IV. COMMITTEES OF THE BOARD
Section 4.1. Creation. The Board of Directors may designate, at any meeting of the Corporation, two or more directors to constitute standing or ad hoc Committees of the Board. Each Committee shall select from among its number a Chairman. In addition to the foregoing Committees, the Board of Directors or the Chair may appoint one or more directors and/or one or more other persons, not directors, to serve as one or more advisory committees, but which shall
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Nominations | p. 11 have no power to exercise any power of the Board of Directors, and the provisions of Sections 4.3, 4.4, and 4.5 of this Article shall not apply to such advisory committees.
(a) Executive Committee. Except as otherwise specified in the Articles of Incorporation or these Bylaws, an Executive Committee, the membership of which shall consist of the officers of the Corporation (including the President), shall act on behalf of the Board of Directors between meetings of the Board.
Section 4.2. Powers. A Committee shall have such functions and may exercise such power of the Board of Directors as may be delegated lawfully and as provided in the resolution or resolutions creating such Committee or Committees; provided, however that the creation of such Committee or Committees shall not operate to relieve the Board of Directors, any individual director, or the officers of any responsibility imposed on such persons by law. Notwithstanding any provision of this Article or these Bylaws to the contrary, no Committee shall have any power to:
(a) Fill vacancies on the Board of Directors or any of its Committees.
(b) Amend the Articles of Incorporation.
(c) Adopt, amend or repeal the Bylaws.
(d) Approve a plan of merger, approve a sale, lease, exchange or other disposition of all, or substantially all, of the property of the Corporation, other than in the usual and regular course of affairs of the corporation.
(e) Approve a proposal to dissolve the Corporation.
Section 4.3. Vacancies. Vacancies on Committees shall be filled by the Board of Directors.
Section 4.4. Meetings, Notices and Quorum. All Committees other than advisory committees shall have the same requirements for:
(a) Meetings and Notices;
(b) Quorum; and
(c) Action Without a Meeting as those set forth in Article III with respect to the conduct of business by the Board of Directors, except that Committees shall not be required to hold annual meetings.
Section 4.5. Minutes. Each Committee shall keep regular minutes of its proceedings and report the same to the Board of Directors, and such minutes shall be retained with the permanent records of the Corporation.
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Nominations | p. 12 ARTICLE V. OFFICERS
Section 5.1. Offices, Appointment, Term and Vacancies. The officers of the Corporation shall consist of a Chair, Vice Chair, Secretary and Treasurer, Immediate Past Chair, and the President. The officers shall serve as ex officio members of the Board of Directors with vote. The officers shall also serve as the Executive Committee. The directors shall elect all of the foregoing officers and may elect such other officers, including one or more Vice Presidents, as they shall deem appropriate. Any two or more offices may be held by the same person except that the Chair and Secretary cannot be the same person. Officers (other than the President who shall have a contract) shall be elected at the annual meeting of the Board of Directors for a term of two (2) years, which term may be extended by vote of the Board for up to one (1) additional year, except that the Board may extend the terms of Past Chairs without limit. Each such elected officer shall hold office for the term for which he or she is elected and until his or her successor has been elected and qualified. Any vacancy or vacancies occurring in any office of the Corporation may be filled for the unexpired term at a duly called meeting of the Board of Directors by the affirmative vote of a majority of a quorum the directors voting thereon.
Section 5.2. Chair. The Chair (hereafter “Chair”) shall perform all duties of the Chair. The Chair shall preside at all meetings of the Board of Directors and, subject to the supervision of the Board of Directors, shall perform all duties customary to that office and shall supervise and control all of the affairs of the Corporation in accordance with policies and directives approved by the Board of Directors.
Section 5.3. Vice Chair. In the absence of the Chair or in the event of his/her inability or refusal to act, and the Vice Chair shall performs the duties of the Chair, and, when so acting, shall have all the powers of and be subject to all the restrictions upon the Chair. The Vice Chair shall convene the CEO compensation determination process. The Vice Chair shall perform such other duties and have such other powers as the Board of Directors may from time to time prescribe by standing or special resolution, or as the Chair may from time to time provide, subject to the powers and the supervision of the Board of Directors.
Section 5.4. Immediate Past Chair. The Immediate Past Chair shall carry out the duties assigned to him or her by the Board of Directors or the Chair.
Section 5.5. Secretary. The Secretary shall be responsible for the keeping of an accurate record of the proceedings of all meetings of the Board of Directors, shall give or cause to be given all notices in accordance with these Bylaws or as required by law, and, in general, shall perform all duties customary to the office of Secretary. The Secretary shall have custody of the corporate seal of the Corporation, if any; and he or she shall have the authority to affix the same to any instrument requiring it; and, when so affixed, it may be attested by his signature. The Board of Directors may give general authority to any officer to affix the seal of the Corporation, if any, and to attest the affixing by his signature.
Section 5.6. Treasurer. The Treasurer shall supervise the receipt and custody of the Corporation's funds; cause to be kept correct and complete books and records of account, including full and accurate accounts of receipts and disbursements in books belonging to the
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Nominations | p. 13 Corporation; assume responsibility for all funds and securities of the Corporation; prepare, distribute and retain or cause to be prepared, distributed and retained all reports, records and returns required by law regarding the Corporation's financial status; and perform such other duties as may be assigned to him or her, or specifically required to be performed by him or her, by the Board of Directors or by the Chair.
Section 5.7. President. The Board of Directors shall appoint an President, who shall serve as the chief executive officer of the Corporation and as the administrative head charged with the responsibility of carrying out the policies of the Corporation, proposing programs of work and executing the program authorized by the Board of Directors. The President shall serve at the pleasure of the Board according to the terms of a defined contract. Subject to rules and regulations of the Board of Directors, including the Accounting and Procedures Manual, the President shall have power to designate, appoint, or remove agents or employees of the Corporation and have the exclusive authority to enter into contracts on behalf of the Corporation, except to the extent that the Board of Directors specifically designates other officers to enter into such contracts.
Section 5.8. Agents and Employees. The Board of Directors may appoint agents and employees who shall have such authority and perform such duties as may be prescribed by the Board. The Board may remove any agent or employee at any time with or without cause. Removal without cause shall be without prejudice to such person's contract rights, if any, and the appointment of such person shall not itself create contract right.
Section 5.9. Removal. Any officer (other than the President) of the Corporation may be removed at any time, with or without cause, by resolution adopted by the affirmative vote of a majority of a quorum of the directors then in office. The President may only be removed under the terms and conditions provided in his or her employment contract.
Section 5.10. Resignations. The resignation of any officer shall be in writing and shall be effective immediately upon receipt by the Board of Directors, if no time is specified, or at such later time as the resigning director may specify and the Corporation shall accept.
Section 5.11. Compensation of Officers, Agents and Employees. The Corporation shall not pay any compensation to officers for services rendered to the Corporation, except that officers may be reimbursed for expenses incurred in the performance of their duties to the Corporation, in reasonable amounts. The Corporation may pay compensation in reasonable amounts to agents and employees for services rendered, such amounts to be fixed by the Board of Directors or, if the Board delegates power to any officer or officers or the President, then by such officer or officers or the President, except the President may not set his/her own compensation. The Board may require officers, agent or employees to give security for the faithful performance of their duties.
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Nominations | p. 14 ARTICLE VI. FINANCIAL MATTERS
Section 6.1. Checks. All checks or demands for money and notes of the Corporation shall be signed by such one or more officers and such other persons are designated by resolution of the Board of Directors.
Section 6.2. Annual Budget. The President and/or Treasurer shall submit an annual budget to the Board of Directors at, or prior to, the annual meeting of the Board, which budget may be adopted by a majority of all directors voting thereon.
Section 6.3. Voting Upon Shares of Other Corporations. Unless otherwise directed by the Board, the Chair or President shall have full power and authority on behalf of the Corporation to vote either in person or by proxy at any meeting of shareholders of any corporation in which this Corporation may hold shares, and at any such meeting may possess and exercise all of the rights and powers incident to the ownership of such shares which, as the owner, this Corporation might have possessed and exercised if present. The Board may confer like powers upon any other person and may revoke any such powers as granted at its pleasure.
ARTICLE VII. AMENDMENTS
Section 7.1. Amendment of Articles of Incorporation and Bylaws. The Articles of Incorporation of the Corporation may be amended in whole or in part by a majority vote of the directors then in office pursuant to the procedure outlined in District of Columbia Nonprofit Corporation Act. The Bylaws of the Corporation may be adopted, amended or repealed in whole or in part by a majority vote of the Board of Directors then in office.
ARTICLE VIII. INDEMNIFICATION AND INSURANCE
Section 8.1. Indemnification. To the extent allowed by the District of Columbia Nonprofit Corporation Act, the Corporation shall indemnify any director, officer, employee or agent, any former director, officer, employee or agent, any person who may have served at its request as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise, whether for profit or not for profit, against expenses (including attorneys' fees), judgments, fines and amounts paid in settlement, actually and reasonably incurred by him in connection with any threatened, pending or completed action, suit or proceeding, whether civil, criminal, administrative, or investigative (other than an action by or in the right of the Corporation), to which he or she may be or is made a party by reason of being or having been such director, officer, employee or agent to the maximum extent permitted by law.
(a) The provisions of this Article shall be applicable to claims, actions, suits, or proceedings made or commenced after the adoption hereof, whether arising from acts or omissions occurring before or after adoption hereof.
(b) The indemnification and advancement of expenses provided by this Article shall not be deemed exclusive of any other rights to which such director, officer,
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Nominations | p. 15 employee or agent may be entitled under any statute, Bylaw, agreement, vote of the disinterested members of directors or otherwise, and shall not restrict the power of the Corporation to make any indemnification permitted by law.
(c) The indemnification and advancement of expenses provided by this Article shall, unless otherwise provided when authorized or ratified, continue as to a person who has ceased to be a director, officer, employee or agent and shall inure to the benefits of the heirs, executors and administrators of such a person.
Section 8.2. Insurance. The Board of Directors may authorize the purchase of insurance on behalf of any person who is or was a director, officer, employee or agent of the Corporation, or who is or was serving at the request of the Corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise against any liability asserted against or incurred by him in any such capacity, or which arises out of such person's status as a director, officer, employee, or agent whether or not the Corporation would have the power to indemnify such person against that liability under law.
Section 8.3. Limitations. In no case, however, shall the Corporation indemnify, reimburse, or insure any person for any taxes imposed on such individual under chapter 42 of the Internal Revenue Code of 1986, as amended (the "Code"). Further, if at any time the Corporation is deemed to be a private foundation within the meaning of Section 509 of the Code, then, during such time, no payment shall be made under this Article if such payment would constitute self-dealing or a taxable expenditure, as defined in Section 4941(d) or 4945(d), respectively, of the Code. Moreover, the Corporation shall not indemnify, reimburse, or insure any person in any instance where such indemnification, reimbursement, or insurance is inconsistent with Section 4958 of the Code or any other provision of the Code applicable to corporations described in Section 501(c)(3) of the Code.
Section 8.4. Severability. If any part of this Article shall be found in any action, suit or proceeding to be invalid or ineffective, the validity and the effectiveness of the remaining parts shall not be affected.
ARTICLE IX. CONFLICTING INTERESTS
Section 9.1. Excess Benefit Transaction. No director or officer of the Corporation may engage in any excess benefit transaction as defined in section 4958 of the Code.
Section 9.2. Conflicting Interest. Directors, officers, and certain key employees identified by the Chair in his or her sole discretion, shall disclose to the Board any conflicting interest transactions or divided loyalties which arise, and no director or officer shall vote on any matter that would involve such conflicting interests or loyalties without the approval of the Board. In the event that a director questions whether a conflicting interest of loyalty exists, the issue shall be decided by a majority vote of the directors present and voting, provided that the director in question shall not vote.
Section 9.3. Statement of Affiliation. At the time of their appointment, each director, officer or employee may be asked to complete a "statement of affiliation" disclosing all "related
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Nominations | p. 16 parties" to such director, officer, or employee, including affiliations for the past five years, including disclosure of all such persons who would have a conflicting interest with respect to any transaction between such person and the Corporation. These statements shall also disclose any relevant interest which may pose conflict of interest questions, including any interest, financial or otherwise, in any corporation, organization, or partnership which provides professional or other services to the Corporation. These statements will be kept on file at the Corporation office, and copies will be distributed to all Board members for their reference. These statements will be updated annually in January of each year, and changes shall be noted as they occur.
ARTICLE X. GENERAL PROVISIONS
Section 10.1. Gender. The gender and the number of any word shall be construed to include another gender or number whenever appropriate.
Section 10.2. Principal Office. The principal office of the Corporation shall be located at such place as the Board of Directors may from time to time designate for the transaction of corporate business. The Corporation shall have and continuously maintain a registered office and a registered agent in the District of Columbia. The registered office may but need not, be identical with the principal office of the Corporation. The Board of Directors may change the registered office and the registered agent as provided in the Act.
Section 10.3. Fiscal Year. The fiscal year of the Corporation shall be January 1 to December 31 unless otherwise fixed by action of the Board of Directors.
Section 10.4. Private Inurement. No part of the net earnings of the Corporation shall inure to the benefit of any director of the Corporation, officer of the Corporation, or any private individual (except that reasonable compensation may be paid for services rendered to, or for, the Corporation affecting one or more of its purposes). No director or officer of the Corporation, or any private individual, shall be entitled to share in the distribution of the corporate assets on dissolution of the Corporation.
Section 10.5. Internal Revenue Code. The Corporation shall be a non-profit corporation duly organized under the laws of the District of Columbia.
(a) The Corporation shall obtain tax-exempt status as a charitable organization pursuant to Section 501 (c)(3) of the Internal Revenue Code, and maintain a separate fund exclusively for the Corporation’s purpose(s) and shall take all actions necessary for donations to such Corporation to be deductible by the donor pursuant to Section 170 of the Internal Revenue Code.
(b) The Corporation shall not discriminate in any manner on the basis of race, religion, color, national origin, or sex.
(c) The Corporation may establish other qualifications from time to time.
Section 10.6. Distribution of Assets. Upon dissolution of this Corporation, any assets remaining after payment, or provision for payment, of all debts and liabilities of this Corporation
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Nominations | p. 17 shall be distributed to a non-profit corporation organized under Section 501 (c) (3) of the Internal Revenue Code. Such distribution shall be made in accordance with all applicable provisions of the laws of the District of Columbia.
Section 10.7. Limitation on Activities. No substantial part of the activities of the Organization shall be the carrying on of propaganda, or otherwise attempting to influence legislation, and the Corporation shall not participate in, or intervene in (including the publication or distribution of statements) any political campaigning on behalf of or against any candidate for public office. The Corporation shall not carry on any other activities not permitted to be carried on by an organization exempt from federal income tax under section 501(c)(3)of the Internal Revenue Code of 1886 (the “Code”) or the corresponding provision of any future United States revenue statute, as amended from time to time, or by an organization contributions to which are deductible under Section 170(c)(2) of the Code or the corresponding provision of any future United States revenue statute, as amended from time to time.
Section 10.8. Parliamentary Procedure. All matters of parliamentary procedure will be guided by Sturgis, The Standard Code of Parliamentary Procedure, 4th Ed. (“Sturgis”) to the extent such Code is not inconsistent with any external laws, the Articles of Incorporation, these By-Laws, or any special rules of order the Corporation may adopt.
The foregoing Amended and Restated Bylaws were adopted by the Board of Directors on this day of 25th day of February, 2010.
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Nominations | p. 18
3. 2016 Progress Report
Progress Report
2016
INTRODUCTION Since its founding, PMC has organized all stakeholders in personalized medicine to support the science, policy and business of the field through a diverse group of educational and advocacy activities. As a result, personalized medicine and PMC have grown in import and impact.
While maintaining leadership in education and advocacy as referenced below, PMC expanded its influence in 2016 by assuming responsibility for the Personalized Medicine Conference at Harvard Medical School, which has allowed the organization to broadcast its agenda to an exceptionally broad and sophisticated group of leaders in health care.
EDUCATION
1. PMC defined the science, business and policy challenges facing the field by organizing the 12th Annual State of Personalized Medicine Luncheon Address, delivered by Stephen J. Ubl, President, CEO, PhRMA.
• 150+ people attended the event • As a result of the conversation, news stories in outlets including Politico and Bloomberg highlighted the personalized medicine implications of topics like Medicare’s proposed Part B demonstration and the Institute for Clinical and Economic Review’s value assessments
2. PMC organized a comprehensive discussion of the science, business and policy challenges facing the field at the 12th Annual Personalized Medicine Conference.
• 400+ people attended the event, which had broad media coverage • Speakers included C-suite executives, members of the media and leading investors • Four government officials shared their thoughts on the coming year as attendees considered the landscape for personalized medicine in a new era • Six payers on the program revealed a new interest in and commitment to personalized medicine
3. PMC directed ongoing discussions about personalized medicine by defining developments in the field.
• The Coalition’s analysis of FDA’s 2015 personalized medicine approvals was widely cited by several publications, including GenomeWeb
• An essay in The Journal of Precision Medicine titled “Towards Targeted Therapeutics: The Pharmaceutical Industry and Personalized Medicine” by Edward Abrahams and Stephen Eck documented the industry’s commitment to personalized medicine • Eight regularly occurring essays by PMC authors in Personalized Medicine in Oncology highlighted and analyzed the most significant challenges facing the field • “The Impact of Alternative Payment Models on Oncology Innovation and Patient Care” in Clinical Cancer Research, co-authored by PMC and the other co-conveners of the Turning the Tide Against Cancer Initiative, drew attention to the personalized medicine implications of alternative payment models • An essay titled “Patient and Provider Readiness for Personalized Medicine,” based in part on PMC- commissioned research, published in Personalized Medicine in Oncology by PMC’s Amy M. Miller, Ph.D., and a team of member authors, discussed the landscape for personalized medicine education • Two editions of PMC’s newsletter, Personalized Medicine in Brief, as well as regular email updates reviewed the latest developments in the field and summarized relevant news coverage
4. PMC discussed developments in both science and public policy with its members during five policy committee meetings.
• These meetings featured leaders from FDA, the White House and member organizations as well as panels on coding and value assessment • The meetings set the agenda for the personalized medicine community, regularly bringing together more than 100 of the field’s leaders
5. PMC proposed ideas on how personalized medicine might be advanced through participation in member and non-member events.
• PMC co-organized and co-hosted with the Biotechnology Innovation Organization (BIO) the BIO/PMC Track on Personalized Medicine and Diagnostics at the 2016 BIO International Convention o The event included two networking receptions and seven sessions • PMC increased its international presence through keynote, moderator and panel speaking engagements held in the United States, Germany, Spain and Canada
6. PMC continued to grow the reach of its digital communication tools.
• 18 blogs published by PMC staff members and external thought leaders on Education & Advocacy o Blogs were cited by outlets including Medscape and The Gray Sheet • 100%+ increase in @permedcoalition followers (now totaling 600+)
7. PMC spearheaded a comprehensive effort to understand the best practices to integrate personalized medicine into health care.
• Convened the Health Care Working Group to produce guidelines for implementing personalized medicine in a manuscript titled “Strategies for Integrating Personalized Medicine into Health Care Practice,” which has been accepted for publication in Personalized Medicine • Conducted interviews with key personnel at health care systems nationwide to inform a forthcoming case studies report
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8. PMC helped keep personalized medicine on the health care agenda by securing 120 media mentions.
• PMC’s efforts shaped the arc for many media stories, including some published in The Boston Globe, Bloomberg, STAT News and GenomeWeb
ADVOCACY 9. PMC promoted public policies that encourage investment in personalized approaches to care via meetings with and letters to White House staffers.
• Discussed the future of the field with staffers and other stakeholders during White House events on personalized medicine, including the Precision Medicine Initiative Summit and the “Frontiers Conference” in Pittsburgh • Submitted comments to Vice President Joe Biden in response to the Cancer Moonshot Task Force’s request for information from the personalized medicine community • Regularly provided comments on the importance of innovation in personalized medicine to media outlets including Politico and STAT News
10. PMC promoted regulatory reforms to accelerate the development of personalized medicine products by convening stakeholders to agree on various policy positions.
• Developed PMC’s position on regulating next-generation sequencing by publishing public comments on the FDA’s draft guidance documents for oversight of next-generation sequencing and the use of public human genetic variant databases to support clinical validity • Contributed to the development of a clear and efficient regulatory pathway for companion and complementary diagnostic products by publishing public comments on the codevelopment of laboratory-developed tests • Led an effort to forge a consensus framework for regulating laboratory-developed tests in coordination with the American Medical Association, which led to FDA acknowledging principles for regulation and asking PMC for venues to engage the community
11. PMC defined how personalized medicine can be enhanced through reimbursement policies.
• Engaged CMS in support of policies that encourage coverage and payment of personalized medicine by publishing public comments on its Medicare Part B Drug Payment Model and its preliminary gapfill determinations for multianalyte assays with algorithmic analyses and genomic sequencing • Contributed to the national dialog on value assessment frameworks by inviting an Institute for Clinical and Economic Review (ICER) representative to a PMC policy committee meeting and engaging press outlets including STAT News and GenomeWeb • Successfully negotiated for changes to ICER’s process by submitting comments on ICER’s Value Assessment Framework and Non-Small Cell Lung Cancer Scoping Document • Leveraged the 12th Annual Personalized Medicine Conference to establish relationships with private payers, including Harvard Pilgrim HealthCare, Blue Cross Blue Shield and Humana
SPONSORED INITIATIVE This year, the Coalition also funded and launched the “Clinical and Economic Value of Next-Generation Sequencing” research project.
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The Clinical and Economic Value of Next-Generation Sequencing: A Research Project The Clinical and Economic Value of Next-Generation Sequencing (NGS) research project will examine the value of NGS technologies to both patients and the health system. Partner organization(s) will provide funding and expertise to help develop an impactful, evidence-based research program. In 2016, PMC formed an advisory committee, contracted a health economist as lead researcher and secured 100% of its preliminary sponsorship goal.
SPONSORSHIP OPPORTUNITY The Coalition also positioned itself to launch the Personalized Medicine Education Initiative in 2017.
The Personalized Medicine Education Initiative Through the Education Initiative, PMC will develop a carefully curated, leading personalized medicine resource that can be updated in real time. Partner organizations will provide funding and/or expertise in selecting and developing appropriate content for online publication. In 2016, the Coalition published a proof of concept on its website, formed content partnerships with the Mayo Clinic, Boehringer Ingelheim and NextGxDx, and raised initial sponsorship revenue from Boehringer Ingelheim.
ADMINISTRATION PMC strengthened its Board and sustained its revenues to carry out its mission. The Coalition:
• Recruited and integrated 6 new Board members • Retained 80 percent of current members and recruited 34 new members • Increased revenue by 9 percent to $2.3 million – $500,000 from sponsorships and $106,000 in admission fees from the Annual PM Conference • Piloted revenue growth streams, including funding for specific projects totaling $165,000
Page 4 Click here to download the conference program. CONFERENCE PROGRAM November 15–17, 2016
JOSEPH B. MARTIN CONFERENCE CENTER • HARVARD MEDICAL SCHOOL 77 AVENUE LOUIS PASTEUR, BOSTON, MA 02115
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4. Plans for 2017
Strategic Plan
2017
INTRODUCTION For the last dozen years, PMC has worked to create a friendlier landscape for investment in and adoption of personalized medicine. Personalized medicines now account for a significant component of all new drugs that enter the market each year. Hospital systems now label themselves as “personalized medicine centers” and investments in many areas of personalized medicine have never been greater. Maintaining progress in a changing environment, however, requires a sustained effort. To ensure that past momentum is maintained, PMC has outlined a comprehensive strategic plan for the coming year that runs along the entire spectrum of health care from research and development to the delivery of personalized medicine products. The change of administration in Washington provides an important opportunity to educate new policymakers on the role that personalized medicine plays in health care.
2017 OBJECTIVES Guided by an analysis of the personalized medicine landscape and the PMC board-identified priorities in education and advocacy, PMC has 10 objectives for 2017.
EDUCATION
1. PMC will define the science, business and policy challenges facing the field by organizing the 13th Annual State of Personalized Medicine Luncheon Address: • The event will feature a keynote address by a leader in science, policy and/or business who will share a vision for the future of the field • 150+ attend annually • Past keynote speakers include PhRMA President & CEO Stephen J. Ubl, U.S. Congressman Michael C. Burgess, M.D., and CMS Deputy Administrator for Innovation and Quality Patrick Conway, M.D.
2. PMC will organize comprehensive discussions of the science, business and policy challenges facing the field at the 13th Annual Personalized Medicine Conference. The event will: • Attract leading speakers and a sophisticated audience • Be considered a “must-attend” for those interested in personalized medicine • Include premier networking events
3. PMC will contribute thought leadership and help define the field by: • Publishing a summary and analysis of the 12th Annual Personalized Medicine Conference • Publishing an analysis of FDA’s 2016 personalized medicine approvals
Plans for 2017 | p. 1 • Publishing a retitled and rebranded version of PMC’s signature document, The Personalized Medicine Report • Publishing an annual report to update the community on progress in the field and PMC’s efforts to facilitate that progress • Publishing, on PMC’s website, updated appendices that list personalized medicine therapeutic products and diagnostic tests • Publishing a white paper about how value-assessment programs could and should reflect the rapidly evolving science and clinical practice of personalized medicine • Writing and producing PMC’s publications, including the bi-annual newsletter, Personalized Medicine in Brief, and the monthly Member Update • Publishing a monthly column, “The Last Word,” in Personalized Medicine in Oncology • Writing, inviting and publishing timely thought leadership pieces that call attention to issues facing the field and opportunities to address them on PMC’s blog Education & Advocacy
4. PMC will review developments in both science and public policy with its members during a series of policy committee meetings. • Meetings will feature key policymakers in personalized medicine. 2016 speakers included FDA Deputy Office Director, Personalized Medicine and Molecular Diagnostics Elizabeth Mansfield, Ph.D., ICER Director, Health Economics Rick Chapman, Ph.D., and White House Project Manager, Precision Medicine Initiative Stephanie Devaney, Ph.D. • These meetings will help drive PMC’s 2017 advocacy agenda
5. PMC will offer thoughts on how personalized medicine might be advanced through participation in member and non-member events. • PMC will co-organize and co-host with the Biotechnology Innovation Organization (BIO) the BIO/PMC Track on Personalized Medicine and Diagnostics at the BIO International Convention • PMC will organize a seminar on the science, business and policy issues underpinning personalized medicine at the Tri-Molecular Conference on Personalized Medicine in San Francisco • PMC will partner with the American Association of Cancer Research and Feinstein Kean Healthcare through the Turning The Tide Against Cancer Initiative to produce a national conference educating new policymakers on the state of personalized cancer care
6. PMC will keep personalized medicine on the health care agenda by securing regular media mentions. • PMC will continue to pitch personalized medicine stories and provide interviews, quotes and background materials to trade and mainstream press
7. PMC will spearhead comprehensive efforts to understand the best practices for integrating personalized medicine into health care by: • Publishing the results of its Health Care Working Group’s efforts to outline solutions for integrating personalized medicine into health care systems • Demonstrating how personalized medicine can be integrated into practice by publishing a series of case studies on the topic • Presenting key themes from PMC’s work on the topic at relevant conferences and meetings
ADVOCACY
8. PMC will promote public policies that encourage investment in personalized approaches to care by: • Educating a new administration and Congress on the state of personalized medicine and the implications that policies can have on the field • Encouraging Congressional leaders to ensure that pharmaceutical and medical device legislation encourages innovation and investment in personalized medicine as well as creates value for patients and the health care system
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Plans for 2017 | p. 2
9. PMC will promote regulatory reforms that accelerate the development of personalized medicine products by:
• Helping to develop a clear and efficient regulatory pathway for companion and complementary diagnostic products and a new regulatory process based on curated databases for next-generation sequencing products
10. PMC will define how personalized medicine can be enhanced through reimbursement policies by:
• Engaging CMS to support policies that encourage coverage and payment of personalized medicine technologies and approaches • Working with private payers to advance policies supportive of personalized medicine • Advocating for the consideration and inclusion of personalized medicine principles in value assessment frameworks
SPECIAL INITIATIVES PMC has also identified four projects that could be undertaken with additional resources. They include: 1. The Clinical and Economic Value of Next-Generation Sequencing: A Research Project (funded) The Clinical and Economic Value of Next-Generation Sequencing (NGS) research project will examine the value of NGS technologies to both patients and the health system. In consultation with payers to ensure the significance of the findings, partner organization(s) will provide funding and expertise to help develop an impactful, evidence-based research program.
2. The Personalized Medicine Education Initiative (funding pending) Through its Education Initiative, PMC plans to build a platform of digital communication tools through which it can advance strategic communications efforts in partnership with its members. The tools, which will include a standalone website, branded slide decks and shareable infographics, will permit PMC to become the go-to source for raising awareness of personalized medicine.
3. Advancing Access to Personalized Medicine: A Comparative Assessment of International Regulatory, Reimbursement and Health Technology Systems (funding pending) The white paper titled Advancing Access to Personalized Medicine: A Comparative Assessment of International Regulatory, Reimbursement and Health Technology Systems will establish a ranking system to facilitate the understanding of how regulation, reimbursement and technology assessment policies impact the adoption of personalized medicine around the world.
4. Evidence for Coverage and Payment of Personalized Medicine Diagnostics (funding pending) By convening an expert working group of payers, diagnostic company representatives, patients and providers, PMC will seek to define and agree on the types and levels of evidence that are reasonably necessary for coverage and adequate payment of personalized medicine diagnostics.
ADMINISTRATION To actualize these plans, PMC will continue to strengthen its Board and augment membership revenues to carry out its mission by:
• Recruiting and integrating at least three additional Board members • Retaining 85 percent of current members and recruiting 60 new members to increase total membership to 240 institutions, including an increasing percentage of international members
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Plans for 2017 | p. 3 • Increasing total revenue by 15 percent to $2.66 million, including $1.8 million from membership, $632,000 from sponsorships, and $150,000 from miscellaneous sources and admission fees • Piloting revenue growth streams, including funding for specific projects (see “Special Initiatives” section above)
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Plans for 2017 | p. 4
Clinical and Economic Value of NGS Testing in Cancer Care
BACKGROUND
Introducing a new technology in health care, especially one that proposes to transform medical practice, can be a daunting exercise because, as Machiavelli explained, most people “do not believe in anything new until they have actual experience of it.”
While the rapid decrease in the cost of next generation sequencing (NGS) has opened up new opportunities to analyze cancer tumors to determine what therapies may be most effective, most payers and providers have had too little experience with the proposed new approach to take the lead in the introduction of a new paradigm that links the choice of therapy to the information that can be derived from sophisticated molecular diagnostics such as NGS tests.
Without evidence that it works both for patients in better clinical outcomes and for the health systems that employ it in lower systemic costs, “medicine’s next step,” as President Obama has called it, will come much more slowly than we would like. OBJECTIVE
With a planning grant of $150,000 from Quest Diagnostics, PMC organized a steering committee to develop a proposal that would demonstrate the clinical and economic value of next generation sequencing-based diagnostic testing in cancer care. That proposal, which will evaluate the value, both clinical and economic, of solid tumor NGS-based diagnostic testing to guide targeted therapies in cancer care, is attached. Developed by Scott Ramsey, M.D., Ph.D., at the Fred Hutchinson Cancer Research Center, it will lead to a peer-reviewed publication whose purpose is to provide evidence for developers, payers, and providers that NGS-based diagnostic testing is both clinically useful and economically efficient. As the research proposal states, “The primary hypothesis of this study is that, based on current evidence, multiplex NGS testing can be cost effective from a payer perspective, when compared to the current standard in diagnostic testing (i.e. no testing or selected mutation testing aka “hotspot testing”). RESEARCH OUTLINE
The project will be broken into two phases. The first phase, to be completed in 6-9 months, will consist of development of a value model validated with existing real world data on NGS-based testing in non-small cell lung cancer.
The second phase, to be completed in 18 months, will include an expansion of the value assessment in other major carcinomas for which mutational analysis is prevalent, such as colorectal cancer and/or melanoma, and will also involve a value of information analysis and the identification of factors that significantly impact cost effectiveness of NGS-based diagnostic testing.
The project’s aim is to assess the value of tumor mutation profiling in general, and will not compare technology platforms.
Plans for 2017 | p. 5 A project advisory committee will be formed to guide the project, review progress at various milestones, and ensure the use of appropriate and up-to-date data.
Research will utilize existing data sets and/or ongoing studies to the extent possible – supplemented with collection of data from health system and medical records.
In the first phase of the study, PMC will coordinate a meeting with the research team, advisory committee members, and other partners, to determine what data sets should be explored for use in the study and how we will gain access to these data sets.
A payer advisory committee will also be formed to provide guidance so the project results will be useful in informing the coverage and payment process.
Results of the study will be published in a peer-reviewed journal and disseminated through a robust communications plan to increase awareness and become a resource for decision-makers in government, industry, and health care. CONCLUSION
Many organizations within the personalized medicine community have called for evidence demonstrating the value of NGS-based diagnostic testing. This proposal, whose total cost we estimate will be about $300,000, is PMC’s answer to that call. We invite your sponsorship of this important project. Interested institutions should contact Daryl Pritchard at [email protected].
About the Personalized Medicine Coalition
The Personalized Medicine Coalition (PMC), headquartered in Washington, DC, representing innovators, scientists, patients, providers and payers, promotes the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system.
Plans for 2017 | p. 6 Title: Clinical and Economic Value of Next Generation Sequencing-Based Diagnostic Testing in Cancer Care Hutchinson Institute for Cancer Outcomes Research (HICOR), Fred Hutchinson Research Institute, Seattle.
Background/Hypothesis: The rapid decrease in the cost of next-generation sequencing (NGS) has opened up new opportunities to efficiently analyze cancers to determine which targeted therapies may be most effective. The current challenge for NGS is to gather evidence to address the hypothesis that assessment of multiple cancer alterations (base pairs subs, indels, copy number alterations, and fusions/translocations) prior to choice of therapy leads to better clinical outcomes and/or lower costs of care. Such evidence will likely be necessary to convince payers to reimburse for NGS tests and their interpretation. Currently, there is growing but still limited amount of published literature to demonstrate, characterize or quantify this impact in the context of specific tumors and clinical settings. A project steering committee commissioned by the Personalized Medicine Coalition (PMC) is developing a research plan that can inform the clinical and health economic impact of NGS testing in solid tumors to guide the use of targeted therapies. At this early stage, there is a need to better understand what factors are likely to have the greatest influence on the cost effectiveness of multiplex NGS testing vs. current practice in the context of specific solid tumors and clinical settings. Analytic insight herein is crucial to determine where future studies should be focused to generate a more convincing evidence base for healthcare providers and payers regarding the health economic value of multiplex NGS tests. Therefore, the primary hypothesis of this study is that, based on current evidence, multiplex NGS testing can be cost effective from a payer perspective, when compared to the current standard in diagnostic testing (i.e. no testing or selected mutation testing aka “hotspot testing”). It is also likely that there is considerable decision uncertainty stemming from the factors that most influence the cost-effectiveness of multiplex NGS testing, such that the benefits of undertaking further research outweigh the costs of research investment. Finally, because research funding is limited, we believe that using economic methods to evaluate multiple potential study designs will provide researchers with information that can aid both study prioritization and design. We will apply tools from ‘value of information’ theory to inform decision-making regarding the design of multiplex NGS studies.
Objectives: The objectives of this study are as follows: 1) Develop a decision model, informed with available population, clinical, and economic data, to evaluate the cost effectiveness of multiplex NGS testing vs. usual care in the context of specific solid tumors and clinical settings a. Identify factors that are highly influential in determining the cost-effectiveness of multiplex NGS testing 2) Using value of information theory and the decision model from objective 1, estimate the return on investment of future research comparing multiplex NGS testing to the standard diagnostic approach, with a goal of identifying the most efficient and impactful study designs.
Plans for 2017 | p. 7 The study will focus on advanced/metastatic non-small cell lung cancer (NSCLC) and suggests melanoma1 as a second cancer to study, as those are examples of cancers characterized by multiple identifiable genetic events that predict clinical benefit from target therapies. The study of malignancies with distinct, yet clinically relevant, molecular profiles will provide a broader understanding of the potential impact of NGS on treatment decision-making and clinical and economic outcomes. The model development for each of the two cancers will be phased in time to accommodate a 6-9 month timeline for initial cost-effectiveness results of one cancer and for another cancer in 12 months from start. After specifying the parameter inputs a meeting with the steering committee will be held to discuss and decide on data sets that will be used to inform the model. We aim to first access primary data sources for the analyses, when made available via the PMC network. If such data are not (timely) available, published literature data will be used. For NSCLC relevant cost data have been published by Sabatini et al. (2015). An initial focus on NSCLC as the first of two cancers in phase 1 of the project, therefore mitigates the risk that a lack of data will delay the first analysis. The cost-effectiveness analysis of multiplex NGS testing of the second cancer will be phased in three months after the NSCLC model.
In order to accomplish these goals, the model-based health economic evaluations of NGS testing will be undertaken with the following core tasks: Phase 1: 1) Estimate the potential cost-effectiveness of NGS testing based on current evidence for two cancers 2) Identify factors that most influence the cost-effectiveness of NGS testing, and thus constitute the primary sources of decision uncertainty surrounding NGS testing; Phase 2: 3) Estimate the return on investment of further research to reduce uncertainty regarding the clinical and economic value of NGS vs. current care 4) Prioritize study designs that most efficiently address this decision uncertainty.
Analytical Plan: Task 1: We will develop a decision-analytic model to compare the costs and effects of multiplex NGS testing versus the current standard in diagnostic testing. Current NGS testing platforms assess potentially actionable genomic alterations (base pairs subs, indels, copy number alterations, and fusions/translocations) i.e. genomic events that potentially predict high efficacy from targeted drugs. Examples of actionable genomic events in advanced NSCLC include those occurring in the EGFR, ALK, BRAF, RET, ROS1, HER2, KRAS and MET, meanwhile a number of other genomic alterations are under study. The standard of care for advanced NSCLC requires at minimal upfront testing for EGFR and ALK gene rearrangements, and consideration should be given to BRAF V600E, MET, ROS1, HER2, and RET. Diagnostic results are followed by the appropriate target therapy for cases with a positive test. In melanoma, the standard of care includes at minimum testing for BRAF mutations while consideration should be given to NRAS and KIT, followed by treatment with a targeted therapy in cases of positive test results. The different patient pathways based on testing and (targeted) treatment combinations are depicted in figure 1. This model structure is flexible to consider various cancers, new or other alterations as part of multiplex NGS panels and new treatment options as these may change over time. Task 2: The model will be populated using primary data as may be provided via the PMC network and complemented, where needed, with data derived from a systematic search of the literature. For the latter, a targeted search strategy of the NCBI Pubmed data base will be developed to identify English language papers
1 We are open to consider other cancers, e.g. colorectal or breast cancer, if the committee prefers these over melanoma. A final decision on this may consider, amongst others, the number of actionable mutations, volume of testing and data availability.
2
Plans for 2017 | p. 8 published between 2010 and 2016. The model will be developed such that additional analyses can be done by updating the input parameters as new primary or published data becomes available from further research. Task 3: Using the available data, the model will be programmed to estimate the incremental cost per life year gained and per quality-adjusted life year gained for each of the two cancers. The analyses will primarily be performed from a payer perspective on costs and therefore captures effects and costs on the population level over short and longer term time horizons, i.e. 1 year and lifetime. Specific costs to payers include cost of testing, cost of treatment (including costs related to disease and treatment complications and hospice care). In addition, patient out-of-pocket costs will be estimated, if published data allow. This is relevant as targeted therapies are in general oral and covered under pharmacy benefits, which means higher copays on relatively expensive drugs. Task 4: We will analyze the expected cost-effectiveness of multiplex NGS testing vs current standard in diagnostic testing in two solid tumors (of which one is confirmed to be NSCLC). One-way sensitivity analyses will be done to identify specific input parameters that most influence the incremental cost-effectiveness of NGS. We will also conduct a probabilistic sensitivity analyses (i.e. assign a distribution to each stochastic input parameter based on its estimated mean and standard error and propagating the parameter distributions through the model) to characterize the overall decision uncertainty around the expected cost-effectiveness of multiplex NGS testing versus the current standard in diagnostic testing. The potential impact of heterogeneity in the study population will be assessed by subgroup analyses. Task 5: To estimate the clinical and economic return on future investments in NGS research, we will employ Value of Information (VOI) analysis, a quantitative approach that allows to put a $-value on reducing decision uncertainty by calculating how the consequences and costs of decisions made with the better evidence from a proposed research study might differ from those decisions when made today. VOI metrics generated from the model include: (a) Expected Value of Perfect Information (EVPI), which can be thought of as an upper bound to the value of further research (b) Expected Value of Sampling Information (EVSI) gives the maximum value of information that can be derived from a sample of size n within a particular study design (c) Expected Net Benefit of Sampling (ENBS), takes into account the reality that collecting further information is costly (ENBS = EVSI minus the estimated cost of research) Task 6: To disseminate the findings of this study, we will prepare 2 conference abstracts and 2 journal manuscripts, one reporting on objectives 1 and 2, and one reporting on objectives 3 and 4.
Key Audiences: payers (commercial and public (Medicare, Medicaid)), healthcare providers, researchers and patients
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Plans for 2017 | p. 9 Project Scope and Timeline (for detailed workflow see Appendix 1):
Core Tasks Main Activities and Deliverables (D) Months from Project start Fee Phase 1.1: Development Model 1 (advanced NSCLC) and cost-effectiveness analysis 1.a. Model structure Develop Model structure (NSCLC) 1 $10,000 development D1. Finalized Model structure 2 1.b. Parameters list Draft parameter list 3 $12,500 Identify potential data source(s) for each parameter 4 Steering committee meeting to discuss and decide on data 4 sets that will be used to inform the model 2. Data collection, Model inputs Collect and analyze data for model input 5 $18,000 D2. Model input values table 6 3. Program Model and Run Populate model, run CEA and 1-way sensitivity analyses 7 $15,000 CEA Present results to Committee 7 4. Dissemination & Reporting Draft abstract and manuscript 1 - NSCLC 8 $22,000 CEA - NSCLC D3. Final abstract and manuscript 1 –NSCLC 9 Phase 1.2: Development Model 2 and cost-effectiveness analysis (melanoma or other cancer to be confirmed) 1a. Model structure Develop Model structure 4 $10,000 development D4. Finalized Model structure 5 1b. Parameters list Draft parameter list 6 $12,500 Identify / agree on data source for each parameter 7 2. Data collection, Model inputs Collect and analyze data for model input 8 $18,000 D5. Model input values table 9 3. Program Model and Run Populate model, run CEA and 1-way sensitivity analyses 10 $15,000 CEA Present results to Committee 10 4. Dissemination & Reporting Draft abstract and manuscript 11 $22,000 CEA - Melanoma D6. Final abstract and manuscript 2 12 Phase 2: Value of Information Analysis on Model 1 and 2 5. VOI Analyses Program and Run VOI modules in Model 1 (NSCLC) 10 $24,000 Program and Run VOI modules in Model 2 13 Present VOI results to Committee 16 6. Dissemination & Reporting Draft abstract and manuscript 3 - VOI 17 $20,000 VOI D7. Final abstract and manuscript 3 - VOI 18
Estimated Budget: The overall project budget for this Statement of Work shall not exceed [$199,000]. The project timeline will be July 1, 2016 through December 31, 2017. Research Team and Contact information: Principal Investigator: Scott D. Ramsey, MD, PhD Co-Investigator(s): Lotte Steuten, PhD and Bernardo Goulart, MD, MS and Dr. Watkins (Premera) Primary Contact: Kristy Drury, HICOR, Program Administrator Address: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M3-B232 Email: [email protected] Telephone: 206.667.7608
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Plans for 2017 | p. 10 Figure 1: Proposed decision tree structure
Testing strategy Therapy options Costs and patient outcomes
Overall Survival
Targeted therapy
Death Expected Costs, Life Years, Proportion of Clinical trial (target and population on targeted + non-target therapies) therapy Multiplex NGS testing At 12 months, and over patient lifetime Non-targeted therapy +
Patients diagnosed Hospice Care + with selected solid tumors
Current standard in diagnostic testing + +
Plans for 2017 | p. 11
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Appendix 1: Detailed Workflow Plan
Months from start 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Phase 1.1: Development Model 1 and CEA (NSCLC) Draft model structure Final Model structure Draft parameter list Finalize parameter list Identify data source(s) for each parameter => data sources via PMC => published literature data Collect and analyze data, draft input values table Final input values table Populate the model, run analyses Present CEA results, incl 1-way SA Draft abstract and manuscript Final abstract and manuscript 1: NSCLC - CEA Phase 1.2: Development Model 2 and CEA (melanoma or other) Draft model structure Final Model structure Draft parameter list Finalize parameter list Identify data source(s) for each parameter => data sources via PMC => published literature data Collect and analyze data, draft input values table Final input values table Populate the model, run analyses Present CEA results, incl 1-way SA Draft abstract and manuscript Final abstract and manuscript 2: CEA Phase 2: Value of Information analyses Assign parameter distributions Model 1 (NSCLC) Run EVPI analysis Model 1 Run EVSI & ENBS analyses Model 1 Assign parameter distributions Model 2 Run EVPI analysis Model 2 Run EVSI & ENBS analyses Model 2 Present VOI results based on Model 1 and 2 Draft abstract and manuscript Final abstract and manuscript 3: VOI
Legend: = teleconference = deliverable Plans for 2017 | p. 12
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Education Initiative Informing the Future
INTRODUCTION On January 30, 2015, President Obama described personalized medicine as “one of the greatest opportunities for new medical breakthroughs that we have ever seen.” The scientific community has reason to believe that statement is true, but neither patients nor providers fully understand the field yet — and some people don’t even know it exists.
Survey data suggest that only about a third of patients in the U.S. have even heard the words “personalized medicine,”1 and only 10 percent of primary care physicians say they are very familiar with the field.2 PMC’s Education Initiative will help change those statistics.
Through the Education Initiative, PMC will build an online library of personalized medicine information, with pages about the science underpinning personalized medicine, how personalized medicine improves upon the standard of care and a definitive list of examples demonstrating how personalized medicine can benefit healthy patients and those with a variety of diseases. The Coalition will publicize the website through a series of social media campaigns. Many advocates in the Coalition’s network, which includes more than 250 member institutions, are also committed to amplifying the impact of these documents by sharing them on their own platforms. OBJECTIVE The Education Initiative will make PMC the go-to source for information on personalized medicine. DELIVERABLES PMC will work with its chosen communications partner to develop simple but descriptive information on what personalized medicine is and how it benefits patients and the health system, as well as an online portal for housing that information. PMC will seek to repurpose its members’ educational materials on personalized medicine for the project whenever appropriate.
Deliverables include:
1. Newly designed web pages that communicate: o Information on the science underpinning personalized medicine o How personalized medicine improves upon the current standard of care o A definitive list of detailed examples demonstrating how personalized medicine benefits patients 2. Revisions to the content on PMC’s current website, as appropriate 3. Infographics that can be shared by PMC and its member network to draw attention to the new portal 4. A PMC-branded slide deck that incorporates key information from the portal
1 Miller, AM, Garfield, S, Woodman, RC. Patient and Provider Readiness for Personalized Medicine. Personalized Medicine in Oncology. 2016;5:158- 167. 2 CAHG. CAHG Study Highlights Personalized Medicine Gap: Physicians See Personalized Medicine Role. 2011. Accessed August 27, 2016 from http://www.prnewswire.com/news-releases/cahg-study-highlights-personalized-medicine-gap-126321548.html.
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International Comparative Landscape Analysis
OBJECTIVE
The Personalized Medicine Coalition (PMC) and the European Alliance for Personalised Medicine (EAPM), propose to commission a white paper that will analyze the respective national public policies regarding regulation, reimbursement and technology assessment in the United States, selected countries in the European Union, Japan, China and India in order to understand how those policies shape the international landscape for investment in and adoption of personalized medicine. PROJECT OUTLINE
In addition to outlining public policies in multiple countries, the paper will establish a ranking system whereby progress can be tracked.
The paper will be of interest to investors as well as diagnostic and pharmaceutical companies that must negotiate multiple systems to market their products.
Though more extensive, the paper will build upon an earlier analysis commissioned by PMC, Advancing Access to Personalized Medicine: A Comparative Assessment of European Reimbursement Systems.
The paper will be presented at a public conference in Brussels in the spring of 2016 and again at one in the United States.
PMC and EAPM invite interested parties to send proposals with cost estimates to Edward Abrahams ([email protected]) and Denis Horgan ([email protected]).
About the Personalized Medicine Coalition
The Personalized Medicine Coalition (PMC), headquartered in Washington, DC, representing innovators, scientists, patients, providers and payers, promotes the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system.
About the European Alliance for Personalized Medicine
The European Alliance for Personalised Medicine (EAPM), headquartered in Brussels, brings together Europe’s leading healthcare experts and patient advocates to improve patient care by accelerating the development, delivery and uptake of personalized medicine and diagnostics.
EAPM is calling for the European Commission, the European Parliament and EU member states to help improve the regulatory environment so that patients can have early access to personalized medicine and so that research is boosted.
Plans for 2017 | p. 15
L.E.K. Consulting LLC
1100 Glendon Avenue 19th Floor Los Angeles, CA 90024 USA
T: 310.209.9800 F: 310.209.9125 May 4, 2016 LEK.com
Edward Abrahams, Ph.D. President, Personalized Medicine Coalition
Denis Horgan Executive Director, European Alliance for Personalised Medicine Bangkok
Beijing Dear Edward and Denis
Boston The purpose of this letter (collectively with the Terms and Conditions attached hereto, the “Agreement”) is to confirm our agreement for L.E.K. Consulting LLC Chennai (“L.E.K. Consulting”) to assist The Personalized Medicine Coalition and The European Alliance for Personalised Medicine, (the “Organizations” or “PMC and EAPM”, and Chicago together with L.E.K. Consulting, the “Parties” or each individually, the “Party”) in writing a London white paper that will analyze the respective national public policies regarding regulation, reimbursement and technology assessment of personalized medicine technologies, as Los Angeles contemplated herein and the attached Terms and Conditions. Please let me know if you Melbourne believe it should be modified in any way; otherwise, please sign below and return a copy to me. Milan Sue, Brian and I are very excited to work closely with you in characterizing these issues critical Mumbai to ensuring adoption of personalized medicine approaches globally.
Munich * * * * * * * * New Delhi A. Background New York The Personalized Medicine Coalition (PMC) and The European Alliance for Personalised Paris Medicine (EAPM) are committed to advancing personalized medicine through a breadth of efforts including education, advocacy and policy. Central to both organization’s efforts is San Francisco the view that driving adoption of personalized medicine approaches will improve patient outcomes and drive efficiency in healthcare (vs. trial-and-error, one-size-fits-all approaches). Sao Paulo The PMC and EAPM would like to commission a white paper and supporting research and Seoul analysis to baseline the current state of personalized medicine in selected countries across a Shanghai range of criteria (e.g., regulation, reimbursement, technology assessment), establish a transparent, data-driven country ranking system and create a tracking system by which Singapore progress can be monitored. Sydney Given the firm’s depth in personalized medicine, PMC and EAPM asked L.E.K. Consulting to propose how we can support the effort. Tokyo
Wroclaw Plans for 2017 | p. 16
PMC and EAPM May 4, 2016 Page 2
B. Objectives1 The objective of this project is to develop a white paper that characterizes the personalized medicine landscape (focused on research, regulatory, reimbursement and technology assessment) and benchmarks select countries across a consistent set of objective metrics that would be represented in an index. Sub-objectives include: Aggregate an objective set of landscape data and metrics important in demonstrating adoption and investment in personalized medicine o Landscaping information for how the various country systems work (policies, agencies, stakeholders, process, incentives) in areas such as: . Regulatory . Reimbursement . Technology assessment . Organizational (Hospital uptake) – this will be on a best efforts basis considering available data (we will not perform primary research to understand organizational update) o Objective metrics which may help contrast investment, drivers and adoption of personalized medicine approaches across countries, such as: . Research funding and programs going specifically into personalized medicine (e.g., Genomics England, MVP) . Personalize medicine therapy approvals . Personalized medicine therapy and diagnostics reimbursement policies and levels . Relative sales of personalized medicine therapeutics and diagnostics Baseline and rank countries against key personalized medicine metrics (to be updated longitudinally to demonstrate forward progress) Highlight key issues holding back adoption of personalized medicine in general and country-specific Identify potential solutions / calls to action which may help accelerate personalized medicine adoption and working with PMC and EAPM to highlight potential policy implications
1 By its signature below, PMC consents to and agrees that L.E.K. Consulting may share information and data related to this project with its global associated L.E.K. Consulting offices.
Plans for 2017 | p. 17
PMC and EAPM May 4, 2016 Page 3
C. Approach and Services Given our experience in similar projects we will execute this project in four modules. 1. White paper content alignment 2. Research and analysis 3. Synthesis and white paper draft development 4. Index Development 5. Update support (optional)
Scoping considerations: Geographic scope: US, EU6 (UK, DE, FR, IT, ES, SW), China, Japan and India Content focused on regulatory, reimbursement and technology assessment although we will consider adjacent topics that may help support country rankings or demonstrate important points around funding, innovation, etc. Access to detailed Rx data through PMC / EAPM members may enable a deeper and more granular analysis
Major tasks include: Completing a kickoff with PMC and EAPM to build alignment on a number of topic and process-related issues: o Guidelines for the paper (audience, tone, length, etc.) o Topics and content, organization, etc. o Key dates and timing to develop drafts, deadlines, etc. o Key hypotheses and issues we would like to support in the paper o Country ranking attributes / metrics o Industry metrics to consider o Medical metrics to consider linked to disease areas/indications Aggregating available secondary data across key topics, including: o Landscape / environment by country (policies, agencies, stakeholders, process, incentives) . Regulatory . Reimbursement . Technology assessment o Metrics which may help compare and contrast drivers and adoption of personalized medicine approaches such as: . Research funding and programs going specifically into personalized medicine (e.g., Genomics England, MVP)
Plans for 2017 | p. 18
PMC and EAPM May 4, 2016 Page 4
. Personalize medicine therapy approvals pathways . Personalized medicine therapy and diagnostics reimbursement policies and levels . Relative sales of personalized medicine therapeutics and diagnostics Performing expert interviews (as needed) to bolster perspectives on key topics outlined above and draw out key unmet needs and issues facing the cause Synthesizing findings and performing key analyses that will form the basis for the article Drafting the white paper, index and iterating with PMC and EAPM Developing update templates, sources and metrics to track Transferring relevant background data, etc. to PMC and EAPM
D. Outputs Specific outputs of the project will include: Aggregated and synthesized view of the personalized medicine landscape by country across key areas of regulatory, reimbursement and technology assessment Analysis of industry and country-specific metrics which will serve as a method to rank and track progress Analysis of medical and country-specific metrics which will serve as a method to rank and track progress Country ranking system with clear input assumptions White paper the PMC and EAPM can disseminate to its members and interested parties
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PMC and EAPM May 4, 2016 Page 5
E. Team, Timing and Compensation Alex Vadas, Sue St. Sure and Brian Baranick will take overall responsibility for this project. An experience engagement manager will manage the project. A team of two professionals from our life sciences practice will be assigned to the project. We may also leverage staff from L.E.K. regional offices (e.g., China and Japan) to perform in-country research. Scoping option are outlined below:
US and EU analysis Regional additions
Countries included US and EU6 China, Japan, India, Canada
Timing (weeks) 6 weeks 2 weeks
Staffing 3 FTEs 1 FTE for 3 weeks per country
Professional fees $248,000 $43,000 per country (CN, JP, IN) $25,000 for CA
Expenses 20% of professional fees
The professional fees quoted herein shall expire and be invalid 30 days after the date first written above, unless this Agreement is executed within such 30-day time period.
Summary Edward and Denis, as we have discussed, we are delighted to be helping you with such a critical issue. If you have any questions about this letter, please don’t hesitate to reach out.
Sincerely yours, Alex Vadas, Sue St. Sure and Brian Baranick
Plans for 2017 | p. 20
Memorandum
To: Edward Abrahams, CEO, PMC
From: Jen Madsen, MPH, Health Policy Advisor, Arnold & Porter LLP
Date: November 8, 2016
Re: Coverage and Reimbursement for Diagnostics in Personalized Medicine
Thank you for the opportunity for Arnold & Porter (A&P) to present this proposal to assist the Personalized Medicine Coalition (PMC) in developing a “playbook” for addressing concerns with insurance coverage for molecular diagnostic testing. This proposal describes the problem statement, objectives, deliverables, and a potential budget and timeline for the project, which would be performed in 2017 or 2018, pending identification of a sponsor, or sponsors or other funding sources, for the “playbook.”
Background
PMC’s diagnostics industry members, including makers of in vitro diagnostics, clinical laboratories, healthcare providers, and information technology companies, have encountered a number of challenges in the realm of coverage and reimbursement that threaten the advancement of personalized medicine. Over the past five years, changes in Medicare coverage policy and payment rates, implementation of new and more specific billing codes, and payer concerns about over-utilization of some tests have created turmoil in the industry. Beyond insurance coverage (or the lack of it), barriers to the integration of personalized medicine into the standard of medical care in the United States include limited understanding of genetic testing among most healthcare providers, and evolving standards for how much medical evidence is “enough” to support a new technology’s adoption.
Many of those challenges are documented in the PMC’s 2014 white paper, The Future of Coverage and Payment for Personalized Medicine Diagnostics, including Medicare Administrative Contractor (MAC) Palmetto GBA’s MolDx technical assessment program, the Centers for Medicare and Medicaid Services (CMS) gap-filling process for setting Medicare payment rates for tests using next-generation sequencing and algorithmic analyses, and changes to the Current Procedural Terminology® (CPT®) codes for molecular pathology tests. But since its publication, Congress has passed two
77034262v1 Plans for 2017 | p. 21 significant pieces of legislation that will reshape the coverage and reimbursement landscape for personalized medicine diagnostics over the next few years.
The Protecting Access to Medicare Act of 2014 (PAMA) creates a new pathway for advanced diagnostic laboratory tests (ADLTs) to receive Medicare reimbursement at their launch prices when initially introduced to the market, and thereafter based on private payer rates that reflect tests’ value. Proponents of the legislation believed that this policy would set market-based rates for new tests more quickly than the coding, coverage and payment processes it replaced, but so far CMS’ implementation of the law has left many stakeholders doubting that outcome. Further, over the past two years CMS has announced preliminary payment cuts of up to 90 percent for tests that Medicare has reimbursed for many years and are the standard of care. Monitoring the impact of PAMA on the market for innovative diagnostic tests is a critical priority for PMC.
In the second potentially game-changing new law, the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), Congress has made a $500 million investment to encourage healthcare professionals to adopt alternative payment models (APMs) such as bundled payments and accountable care organizations, and to reward high-quality, low- cost care and the use of electronic medical records. As the individuals with the responsibility of ordering diagnostic tests and using their results to make treatment decisions, healthcare professionals are central to the adoption of personalized medicine. As described in PMC’s 2015 white paper, Paying for Personalized Medicine: How Alternative Payment Models Could Help or Hinder the Field, PMC and its members are monitoring how payment and delivery reforms affect access to personalized diagnostics. As MACRA implementation proceeds in 2017 and 2018, PMC will want to understand how APMs are affecting medical innovation.
Both MACRA and PAMA set a new course for coverage and reimbursement policies for innovative diagnostic tests that will shape the future of personalized medicine for PMC members and, more importantly, for patients. Ensuring that patients receive the right test and treatment at the right time, tailored to their individual genomic profile and personal preferences, will be enabled by a learning healthcare system that will pay for value, based on evidence. The shift is already underway, but ensuring that it does not stifle innovation is a critical priority for PMC and its members.
Objectives
With both PAMA and MACRA being implemented simultaneously, the purpose of this project is to develop a framework and recommendations for creating a value-based market for diagnostics in personalized medicine. This project will engage payers in a dialogue with the diagnostics community to identify mutually agreeable solutions that will help personalized medicine retain the progress made over the past decade and maintain that momentum in the future.
PMC members in the diagnostics community have made incremental progress toward a value-based reimbursement system, such as PAMA’s potential for market-based pricing and Medicare’s “coverage with data (registry) development” pathway. However,
- 2 - Plans for 2017 | p. 22 common-sense policies, such as insurers’ covering a pharmacogenomic test that appears on the FDA-approved labeling of a new drug, or covering testing of family members when an individual is diagnosed with a preventable inherited disease, are currently the exception, not the rule.
We will invoke the convening power of the PMC to establish a consensus-based set of recommendations for improving coverage and payment policy for molecular diagnostic tests so that all patients have access to the right test at the right time, and are able to benefit from new therapies.
The specific goals for the project include the following:
I. Inform the Discussion with Data. The HHS Office of the Inspector General (OIG) recently reported that Medicare’s Clinical Lab Fee Schedule payments for molecular pathology tests declined by 44% from 2014 to 2015.1 Facing such a dramatic drop in one of the largest markets for molecular diagnostics, the PMC and its members should understand why the decline occurred, which patients and tests were most affected, and put this data point in context by examining trends in data from other payers and in other years.
The PMC will commission an analysis of Medicare, Medicaid, and private payer claims data by a reputable and independent firm that examines which patients are receiving molecular diagnostic testing, using the most recent nationally representative data available. The analysis will examine the extent to which disparities exist among children, adults, and elderly Americans based upon their demographics, geography, insurance coverage, and common categories of testing (e.g. screening, companion diagnostics, etc.) A&P will work with the firm performing the claims analysis to draft an issue brief describing the findings. The issue brief will arm PMC with data that will illustrate the challenges at the population level and inform policymakers and the public about the need for policy adjustments to prevent disparities and ensure access to medically necessary testing.
II. Convene a Working Group. The PMC has few payer members, and needs their input to identify shared solutions. We will recruit key representatives of the payer community to participate in a working group with PMC members.
Several thought leaders from health plans with national reach will be addressing PMC members at the 12th Annual Personalized Medicine Conference; we anticipate inviting them and other contacts of the A&P team to participate (without attribution, if they so desire) in the working group.
With PMC staff, A&P will identify representatives of PMC’s members across a range of stakeholders, including patient advocacy groups, healthcare providers, and the
1 HHS OIG, Medicare Payments for Clinical Diagnostic Laboratory Tests in 2015: Year 2 of Baseline Data, September 2016. Available at https://oig.hhs.gov/oei/reports/oei-09-16- 00040.pdf.
- 3 - Plans for 2017 | p. 23 many players in the life sciences industry focused on in vitro diagnostic devices, biologics and drugs, laboratories, and information technology.
We anticipate recruiting individuals who have recently left government as advisors to the process, potentially including some who are not PMC members.
While participation by representatives of CMS and MACs may be solicited as input to the process, those individuals will not be members of the working group. We will set ground rules for discussion that will foster collaboration amongst all of the participants.
III. Solicit Specific Examples to Make the Case. We will solicit the input of each working group member to describe the opportunities and challenges of covering and paying for personalized diagnostics from their perspective. Each working group member will be asked to contribute internal data, analyses of the coverage landscape, and specific case examples to supplement the data analysis in (I) above. Submitting case examples will not be a prerequisite for participation in the working group, but will be encouraged to round out the working group’s perspectives on how to interpret the claims analysis.
IV. Listening Sessions with Payers. We will facilitate a series of listening sessions among members of the working group, to be conducted by conference call every two weeks for a total of approximately eight weeks. On each call, representatives of specific stakeholder groups from within the PMC’s membership (e.g. patient advocates, healthcare providers, life sciences, and information technology) will be asked to present their views on coverage and reimbursement challenges, supporting data or case examples, and recommended solutions, and to engage in a dialogue with payers on the working group about their recommendations. While presentations by members of the working group will be encouraged, they will not be required. PMC members may also participate in the presentations if they so desire, even if their organization is not represented on the working group.
V. Develop Shared Solutions. Based upon the analysis in the issue brief, specific case examples, and listening sessions, we will draft a brief set of principles for value- based reimbursement for diagnostics, including recommendations for ways that PMC and its members can advance the field. Those could include new collaborations amongst private entities, advocating for changes in regulatory policy, and seeking new legislation. Members of the working group would have the opportunity to review and comment on the draft recommendations. We will complete one round of edits.
Following agreement on the principles, we will draft a white paper that will synthesize the analysis, case examples, and listening sessions to support the key recommendations. We will circulate the draft white paper to members of the working group and to the broader PMC membership for review, and will make two round of edits.
Additional deliverables to support the white paper will include a slide presentation, a press release describing the findings and principles, and talking points for PMC members who wish to comment to the media following the release. The author(s)
- 4 - Plans for 2017 | p. 24 of the deliverables will participate in a PMC-convened press briefing to introduce the report and discuss the recommendations.
Deliverables and Timeline
To summarize, the deliverables for the project and timelines for each are shown in the table below:
I. Claims data analysis, including multiple payers and TBD, pending identification of multiple years of data. This analysis will be performed by appropriate firm and datasets another firm, to be determined. Arnold & Porter has relationships with several consulting and actuarial firms that perform analyses of this type, and would assist PMC in scoping and managing the project, to the extent necessary. II. Draft issue brief describing findings from claims analysis. 2-4 weeks, depending upon The issue brief may be drafted by the analytic firm, Arnold & complexity of the claims Porter, or both, depending upon the capabilities of the analysis. selected firm. III. Recruit working group members from the payer 2-4 weeks, depending upon community and PMC membership, establish ground rules for extent to which working group discussion, and schedule listening sessions. members have been recruited in advance by PMC. IV. Solicit case examples from PMC members using a 2-4 weeks, depending upon standardized questionnaire we will design with the input of response from PMC members PMC staff. Arnold & Porter will work with PMC members and volume of responses. to the extent necessary to negotiate what information will be included in any public documents. V. Facilitate four listening sessions via conference call with 8-10 weeks, depending upon payer and PMC representatives of the Working Group. avoidance of Federal holidays, Develop an agenda for each call, identify speakers and vacations, etc. discussants, and summarize key points from discussion. VI. Draft set of principles / recommendations based upon 2-3 weeks for drafting, 1-2 the claims analysis, case studies, working group discussions, weeks for edits, 3-5 weeks total. and understanding of the political environment; including one round of edits. VII. Draft white paper that synthesizes the rationale for the 3-4 weeks for drafting, 2-3 recommendations. Circulate for review by working group weeks for edits, 5-7 weeks total. members and PMC members, including one round of edits. VIII. Slide presentation, talking points, and press release to 1-2 weeks (concurrent with support press briefing. edits to white paper) IX. Presentation at press briefing. TBD. Total Timeline: 23 - 36 weeks (~ 6-9 months)
- 5 - Plans for 2017 | p. 25 Budget
The terms of our letter agreement of October 13, 2015 set forth our mutual understanding as to the basis on which Arnold & Porter will represent the Personalized Medicine Coalition on those matters upon which we may mutually agree.
For this matter, we will bill you monthly at our standard hourly rates. Jennifer Madsen’s billing rate is $455 per hour. Hourly billing rates for other A&P team members, including Tom Gustafson, PhD, Dan Kracov, Paul Rudolf, MD, and Allison Shuren, are available upon request.
We estimate that the budget for this project, excluding the claims analysis in Section I, may be in the range of $90,000 to $120,000. We anticipate that the claims analysis could add $75,000 to $130,000 to the budget for this project. We have not initiated discussions with firms who could perform the claims analysis in Section I, but would be pleased to do so at your request.
If you have any questions about this proposal, please don’t hesitate to contact me. Thank you for the opportunity to work with the PMC on this important project.
- 6 - Plans for 2017 | p. 26
Personalized Medicine in Value Assessment
Frameworks
REQUEST FOR PROPOSALS
PMC is currently seeking proposals for the development of a white paper that examines how respective value assessment frameworks consider and impact personalized medicine. The white paper will also provide an analysis of how value frameworks can incorporate and support personalized medicine along with a contrasting breakdown of how value frameworks could undermine personalized medicine and quality health care. We encourage the inclusion of recent examples of how value frameworks have taken into consideration, or failed to take into consideration, personalized medicine value drivers. Prospective researchers should consider including potential recommendations for framework developers.
PMC’s interest in this topic is driven by a concern that some value assessment frameworks focus solely on therapeutics without considering related components of care that affect treatment value, such as diagnostics and patient engagement, and that many also fail to account for evolving value over time, i.e. the true value of a treatment is never known at launch but rather becomes clearer years later.
SUBMISSION GUIDELINES
Proposals should be 3-5 pages with the possibility to expand and revise after initial review, and should include an explanation of project objectives, an overview of the proposed approach to the project, and a description of the project’s overall value. The proposal should also include a list of the team members, a tentative project timeline, and project budget. The white paper will address all the points listed above, provide a significant contribution to the ongoing national value framework dialogue, be completed during the first quarter of 2017, and reflect a budget of between $25k - $50k. PMC will handle formatting and production of the white paper. We encourage submissions by December 23, 2016.
If you have any questions, please contact Daryl Pritchard at 202 787-5912 ([email protected]).
ABOUT PMC’S RESEARCH PROJECTS
Personalized medicine must overcome numerous hurdles in areas such as regulation, reimbursement, education and clinical integration of personalized medicine advances before it will lead to better health care for patients and improvements to the health care system.
Guided by an analysis of the personalized medicine landscape and our mission to educate, advocate, and form a consensus among stakeholders interested in advancing personalized medicine, PMC highlights the issues facing personalized medicine, facilitates the development of principles for integrating personalized medicine into health care, and promotes public policies that encourage investment in personalized approaches to care.
About the Personalized Medicine Coalition
The Personalized Medicine Coalition (PMC), headquartered in Washington, DC, representing innovators, scientists, patients, providers and payers, promotes the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system.
Plans for 2017 | p. 27
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Plans for 2017 | p. 28 Turning the Tide Against Cancer Through Sustained Medicine Innovation 2017 Conference Prospectus
The challenge of sustaining progress against cancer while facing the economic imperative to provide value to patients has never been more important. The Turning the Tide Against Cancer Through Sustained Medical Innovation initiative is working to meet this challenge, and will convene a national conference on Tuesday, June 27, in Washington, D.C. This conference, Turning the Tide’s third such National Conference, will be a solutions-oriented discussion of concrete policies that support innovation and patient-centered care while addressing rising healthcare costs.
Convened by the Personalized Medicine Coalition, American Association for Cancer Research, and Feinstein Kean Healthcare, the conference will bring together leaders from across the scientific, clinical, regulatory, biopharmaceutical, and patient communities to explore solutions that foster continued innovation and deliver better outcomes for patients.
Patients are the key beneficiaries of our progress against cancer. Indeed, patient-centered care has become the focus of many public and private initiatives aimed at speeding innovation and improving the efficiency and effectiveness of cancer care, including the Precision Medicine Initiative (PMI), Vice President Biden’s Cancer ‘Moonshot’, 21st Century Cures, and tools used to support clinical decision- making. However, meaningful patient involvement and engagement in many of these activities is limited. Turning the Tide’s 2017 National Conference will explore the role of the patient from research and development to the delivery of care, and will delineate strategies for how to involve patients meaningfully in the development of solutions to address the major issues facing cancer research and care today.
Specifically, the conference will convene the stakeholder communities to identify policy pathways related to the following areas:
• Where does oncology innovation stand and where is it headed under a new Administration? • What is the patient’s role in innovation as the key beneficiary of value-based care? • What tools can we leverage to incentivize patient-driven value in oncology care?
The conference will highlight key advances in cancer science and clinical care and identify and build support for policy pathways to accelerate progress toward a patient-centered, high-value system of care.
Plans for 2017 | p. 29
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Plans for 2017 | p. 30 November 28, 2016
Edward Abrahams, Ph.D. President Personalized Medicine Coalition 1710 Rhode Island Ave. NW, Suite 700 Washington, DC 20036
Dear Ed,
Thank you again for meeting for lunch last week and I hope to have the opportunity to assist you and the Personalized Medicine Coalition (PMC) with its education and advocacy programs in Washington. It’s been a pleasure to have been involved with the PMC in a variety of ways since its inception and I very much look forward to assisting you and your colleagues during this time of transition.
Cavarocchi.Ruscio.Dennis Associates, LLC (CRD Associates) has over 35 years of demonstrated experience in health policy and has successfully collaborated with partners both within government and among non- governmental stakeholders. Our areas of expertise include strategic planning, congressional appropriations, the authorizing legislative process, agency program implementation and regulation, grassroots advocacy, direct lobbying, and relationship-building with patient and provider communities.
CRD Associates has strong relationships with members of Congress and their staff as well as at all federal health- related agencies such as senior level contacts in the White House Office of Science and Technology Policy, the Office of the Secretary at the Department of Health and Human Services, the Office of the Commissioner at the Food and Drug Administration, the Department of Veterans Affairs, the Office of the Director at the National Institutes of Health (NIH) and in numerous programmatic divisions within the Centers for Disease Control and Prevention and the Centers for Medicare and Medicaid Services. Within the NIH, CRD Associates offers strong working relationships with extramural and intramural divisions of interest, including the National Human Genome Research Institute and the National Cancer Institute.
With the acquisition of HealthFutures, LLC in 2009, CRD Associates gained a strong presence in the genomics and personalized medicine field, including the addition of a board-certified genetic counselor. Our talented and experienced government relations team is well-positioned to afford PMC with a unique perspective and understanding of the challenges facing the genomics and personalized medicine field.
Scope of Work: CRD Associates with assist and provide guidance to the PMC with its federal policy, education, and advocacy programs as it searches for a new Vice President of Policy. Specifically, CRD Associates will provide the following services.
Plans for 2017 | p. 31 Part 1: Monitoring and Surveillance of Policy Changes CRD Associates will monitor Congressional, Federal Agency, and non-governmental stakeholder activities and actions that are relevant to PMC’s interests including oversight of laboratory developed tests, reimbursement of clinical diagnostic tests, the Precision Medicine Initiative, Cancer Moonshot, and more. If there is an opportunity to provide public comments to Congress or a Federal Agency, CRD Associates will work with the PMC to draft comments and ensure successful submission. At PMC’s request, CRD Associates will attend meetings, workshops and conferences and provide written summaries of the proceedings. Last, CRD Associates will assist with the drafting of the quarterly Policy Brief.
Part 2: Integrated Communications and Guidance CRD Associates will engage in regular biweekly conference calls to maintain continued communication, strategic guidance, and track our progress in completing the scope of work. Additionally, CRD Associates will be available daily by email or telephone for urgent needs, and will monitor government activity of interest to PMC and provide an assessment of implications and recommendations for response for any new initiatives or announcements in a timely manner.
Part 3: Strategic Assessment of the Policy Landscape CRD Associates believes that the central component of any successful lobbying strategy is a cohesive and collaborative government relations strategy. CRD Associates will convene up to a half day strategy session with PMC to learn about the organization’s interests, advocacy goals, and policy needs. During this session, CRD Associates will also provide an overview of the anticipated policy landscape in the new administration and Congress related to policy areas of interest to personalized medicine. Following the overview, CRD Associates will facilitate a discussion on the range of opportunities to influence this area of policy and will develop a written assessment of the landscape that will identify key stakeholders, opportunities for engagement, priority areas, and other needs.
Part 4: Congressional Briefing The best way to connect with many Congressional offices simultaneously is to hold a briefing on Capitol Hill on a topic of relevance to your needs. CRD Associates will work with the PMC to develop an agenda and identify partners such as a Congressional Caucus (if desired), facilitate the request to partner, and manage all communications. We will also handle all logistics of hosting an event on Capitol Hill, including enlisting a Member of Congress to reserve space, draft invitations and materials, advertise the event, order catering, and ensure compliance with Federal ethics laws and procedures. CRD Associates will work to ensure the event is well attended and complete all follow-up needs.
Part 5: Candidate Search for Vice President of Policy CRD Associates will help publicize the job description for the Vice President of Policy, search its contacts, and conduct additional outreach to actively assist with the search for a strong candidate for this vacancy. We will make recommendations for candidates and assist with the review and screening of applications as well as interviews of potential candidates.
Part 6: Relationship-Building and Outreach to Stakeholders (additional $9500 per day of meetings) With a new Administration and new Congress beginning in 2017, it is important for the PMC to build and maintain its relationships and presence among policymakers in Washington. If requested, CRD Associates will schedule meetings with congressional offices (approximately five per day) and at federal agencies (approximately two per day) whose actions could affect the PMC’s scientific, regulatory and other interests. We will handle all scheduling, advance preparation, and follow-up needs from those meetings.
Plans for 2017 | p. 32 Principals: Jennifer Leib will be the lead principal on this agreement and Megan Anderson Brooks and Lyle Dennis will also assist with this scope of work. Their biographical sketches are enclosed for your review. Other CRD Associates personnel will be utilized on an as-needed basis.
Budget: CRD Associates works on a monthly retainer that reflects the scope of work and for Parts 1-5, we propose a six- month agreement commencing on January 1st with a monthly retainer of $10,000. If the PMC would like assistance with meetings with policymakers and other stakeholders, CRD Associates will provide these services on a project-based retainer of $9,500 per day of meetings. CRD Associates also assesses a $500 monthly administrative fee to cover out-of-pocket expenses such as long-distance phone and fax charges, printing and copying costs. Catering costs associated with a briefing or reception will be paid for by PMC. Any travel outside of the Washington, DC area will require prior approval and be reimbursed by PMC.
Either party may cancel this agreement upon thirty (30) days written notice to the other party.
Ethics Statement: Since its founding in 1980, CRD Associates has operated under a rigid code of ethics that recognizes that our clients’ constitutionally guaranteed rights to try to influence public policy confer on us an obligation to act always in the highest ethical and moral manner. Whether dealing with Congress, the Executive Branch or other organizations, all members of CRD Associates are committed to maintaining the highest ethical and professional standards and our results-oriented approach to government relations always puts a premium on serving our clients with honesty and integrity.
As mandated by the Honest Leadership and Open Government Act of 2007 (P.L. 100-81), we register the names of each organization we represent with both the House and Senate and file quarterly disclosure reports which are available for public viewing. All members of our firm receive ethics training annually and act in compliance with the HLOGA and all related regulations.
Thank you again for your consideration of our proposal and we look forward to discussing this in more detail with you. If you agree to the terms of this proposal, then this letter may also serve as our letter of agreement. If so, please initial next to the desired budget option and sign and return one copy for our records.
Sincerely,
Cavarocchi.Ruscio.Dennis Associates, LLC
Lyle Dennis Jennifer R. Leib Partner Senior Vice President
Personalized Medicine Coalition
______Edward Abrahams, Ph.D. Date President
Plans for 2017 | p. 33
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Plans for 2017 | p. 34 Jennifer Leib, Senior Vice President
Jennifer Leib, Senior Vice President, joined CRD Associates in 2009 when it acquired HealthFutures, a government relations and public policy firm that she co-founded. Her practice areas include:
• Patient advocacy organizations • Scientific professional associations • Diagnostic industry and clinical laboratories • Pharmaceutical and biotechnology companies • Venture capital and investment firms
Jennifer’s clients are innovators of disruptive technologies that are fundamentally changing the way research is done, the way medicine is practiced and the way health care is delivered. Board certified in medical genetics, Jennifer also advises clients in the rapidly growing field of personalized medicine to help them actively engage in the discussions driving the adoption of those practices and technologies. She helps clients navigate the evolving regulatory and reimbursement landscape for targeted therapeutics, laboratory-based diagnostics, and mobile and digital health technologies. Jennifer also specializes in assisting young companies and associations with building a brand presence in Washington through relationship building with advocates and policymakers. On behalf of clients, Jennifer builds and manages coalitions, facilitates meetings with government officials, coordinates Congressional briefings, plans policy symposiums, provides strategic planning, engages in direct lobbying, drafts legislative language, and more.
Jennifer previously worked at the National Institutes of Health, the Senate Committee on Health, Education, Labor and Pensions, and in the biotechnology industry. She is frequently invited to present at national and international conferences in the fields of genetics and personalized medicine and has co-authored peer-reviewed publications on genetics policy issues including genetic nondiscrimination and population carrier screening, as well as scientific publications stemming from her research at the NIH. Jennifer holds a master's degree in genetic counseling from The Johns Hopkins University and a bachelor's degree with honors and high distinction in sociology from the University of Michigan.
You can reach Jen Leib at [email protected]
Plans for 2017 | p. 35
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Plans for 2017 | p. 36
Vice President of Public Policy
The Personalized Medicine Coalition (PMC), a dynamic membership-based education and advocacy organization, seeks a Vice President of Public Policy to promote and advance the principles of personalized medicine across the broad spectrum of decision makers responsible for the future of health care. The selected candidate will be responsible for leading PMC’s public policy strategy; building awareness and understanding of personalized medicine and its value to health care; articulating and communicating developments in the field; identifying and addressing barriers to it; and developing and promoting consensus-driven coverage, payment, regulatory and legislative policies. The position reports to the President.
Job Responsibilities:
Public Policy Leadership • Provide analysis of policy proposals for PMC’s strategic planning and activities. • Identify activities for membership engagement and coordinate planning. • Develop consensus policies and positions to strengthen and advance personalized medicine and communicate them to Congress and executive agencies. • Identify new areas for PMC projects and policy discussions. • Plan, coordinate, and run PMC’s Public Policy Committee meetings. • Envision, develop and lead PMC stakeholder working groups designed to address a pressing policy issues. • Represent PMC and deliver presentations at regional, national, and international conferences, meetings, to government and to the press.
Project Management • Develop partnerships, plan, and execute policy oriented projects and initiatives. • In consultation with member organizations and other health policy experts, coordinate policy research, education, and advocacy initiatives meant to strengthen and advance personalized medicine. • Write or manage the preparation of papers and presentations on personalized medicine policy issues that are intended for both technical and non-technical audiences.
Content Development • Identify developments in personalized medicine, and prepare reports, presentations, media, and meeting materials as necessary that provide a critical interpretation of what it means to the field. • Prepare PMC public comments in response to research and policy documents issued by FDA, NIH, CMS and other government, quasi-government, and private institutions. • Develop and continuously update content for PMC’s website and other communications tools in coordination with the communications head.
Plans for 2017 | p. 37 Alliance Development • Engage with PMC member organizations to understand and respond to issues and concerns that affect the field of personalized medicine. • Build collaborations with representatives from FDA, NIH, CMS, AHRQ, HHS and other federal agencies that develop and administer policies related to personalized medicine. • Identify and help recruit potential new PMC Members.
Communications • Identify and prepare content for PMC communication articles, newsletters, blog posts, and promotional materials. • Provide appropriate scientific and policy perspectives and opinions in response to media requests as necessary. • In coordination with communications head, develop stories that advance personalized medicine. • Engage social media on policy issues in coordination with the communications head.
Qualifications and Experience:
• Enthusiasm for PMC’s mission. • Background in personalized medicine, health care, biotechnology, and/or health policy with experience working with the pharmaceutical and diagnostics industries or with health delivery systems. • Ability to translate scientific and medical complex concepts to broader audiences. • Experience in the federal government or direct understanding of how government entities operate and interact on health policy issues. • Strong project management skills, including the ability to concurrently manage multiple projects with adherence to timelines and budget and quality. • Strong writing, editing, and strategic thinking skills. • Sense of humor • Willingness to travel to related seminars, conferences, meetings, etc. • Advanced degree (doctoral-level preferred) in related field and 5-7 years experience.
Plans for 2017 | p. 38 KAYLASMITH www.kaylabrennansmith.com EDUCATION
VirginKSia Tech, 2015 WORK EXPERIENCE B.S. The Advisory Board Company Washington, D.C. Professional sales minor Chief of Staff | July 2016 – Present • Managed a team of seven associates that achieved 114% of team scheduling goal, SKILLS/EXPERTISEGPA: 3.5 assisting the Education Advisory Board team in surpassing annual revenue target • Strong attention to detail and • Trained and developed Marketing Associates, establishing strong business fundamentals including sales, oral & written communication, time management, and focus on task completion project management skills • Demonstrated ability to work with • Motivated staff to exceed goals and think strategically about their internal business and support cross-functional Marketing Associate | July 2015 – June 2016 project teams • Identified strategic business opportunities by managing a strategic plan across one • Ability to manage multiple year projects simultaneously and • Facilitated conversation with High Level Executives including Chief Healthcare Executives with demonstrated knowledge of healthcare knowledge under pressure • Developed targeted campaigns for recruitment to annual prospect events and Proficient in Salesforce • strategic marketing events • Ability to work and manage, • Consistently exceeded 100% of monthly goal effectively, in a team setting • Managed a high volume of data collection accurately and efficiently • Aptitude to learn new skills Delivery Intern | February 2016 – May 2016 quickly and accurately • Gained experience analyzing clients internal data through Excel and CRM tools • Superb communication skills • Shadowed client facing member calls and demonstrations once a week in a three- month span • Outstanding organizational skills • Exceeded expectations refining my member-facing presentation skills and communication style EDUCATION • Established proficiency in excel functions such as pivot tables and VLOOKUP Advanced project management skills assisting in member’s strategy goals Virginia Tech • Blacksburg, VA - 2011-2015 Crimson Fly Social Media Leesburg, VA B.S. Marketing Management & Account Executive Intern | October 2014 – May 2015 Professional Sales • Developed client-centric strategies and tactics given the client's goals, resources and timeline through research, web analytics, and direct marketing campaigns Business Management Abroad • Managed Crimson Fly’s brand through client facing work and presentations • Published content writer of eBooks, blog articles and advertisement graphics on the Antibes, France – Summer 2012 client’s behalf Business Technology, Hospitality and Management • Initiated and preserved relationships with over 30 clients and bloggers with a reach of 30,000,000 monthly page views AFFIILIATIONS PRISM; Pamplin Re-inventing Social Media Blacksburg, VA • PRISM; Pamplin Re-inventing Account Manager | August 2014 – May 2015 Social Media • Managed a $30,000 budget aligning PRISM with the needs of Pamplin College of • Alpha Phi Fraternity Business • Soulstice Female Acapella • Increased and improved our alumni connections through the content creation of monthly newsletters and coordination of networking and social events. • Pamplin College of Business • Created and executed marketing and social media plans for real-world clients Mentor • American Heart Association Virginia Tech Pamplin College of Business Blacksburg, VA Fundraiser Marketing Management T.A. | May 2014 – May 2015 • Girls on the Run Coach • Possessed strong communication skills through presenting bi-weekly to a 500+ person course and answering student concerns during office hours 540-664-8858
• Evaluated and administered to over 1000 cross-disciplinary business students in a [email protected] 3000 level course
Cvent Inc. McLean, VA in/kaylabrennansmith Product Adoption Sales Intern | May 2014 – August 2014 • Developed over 300 leads while matching customer needs to market appropriate Washington, D.C. products and services Plans for 2017 | p. 39 • Professionally trained in B2C sales and product demonstrations • Communicated to external clients determining their business needs
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Plans for 2017 | p. 40
5. Finance and Budget
PMC Budget Nov 10, 2016 Modified Cash-Basis 2015 2016 2016 Actual % 2016 2016 2016 2016 2017
Harvard Harvard % increase Conference Conference from Final to-date Total Budget to budget Projected Base Budget est. Actual Budget projected Revenue: Membership Dues Invoiced $ 1,761,860 1,768,685$ 1,820,000$ 97% 1,766,060$ $ 1,820,000 $ 2,000,000 Non-Renewing Member Dues (135,050) (219,975) (200,000) 110% (302,575) (200,000) -$ 200,000 Membership Dues Outstanding (221,525) Membership-Deferrals Renewing Member Dues-Net 1,626,810 1,327,185 1,620,000 82% 1,463,485 1,620,000 $ 1,800,000 23%
Admission Fees Non-Members 24,600 95,604 140,000 68% 106,608$ 10,000 130,000 $106,608 $ 150,000 41% Friends of the PMC 40,000 30,000 50,000 60% 30,000$ 50,000 $ 52,000 73% Honoraria/Miscellaneous 6,582 10,700 6,000 178% 10,700$ 6,000 $ 7,500 -30% Sponsorship 283,500 433,150 500,000 87% 498,150$ 300,000 200,000 $340,150 $ 632,000 27% Special Projects Dx Value Project 150,000 30,000 160,000$ -100% Education Initative - EU Landscape Analysis - PM Integration Case Study - 3,000 5,000$ Capital Gains/Interest -11,066 58,565 4,000 1464% 35,000$ 4,000 $ 25,000 -29% Total Revenue 2,120,426 1,988,204 2,320,000 86% 2,308,943 1,990,000 330,000 446,758 2,666,500 15%
Expenses: Office Expenses: Bank Charges 6,984 6,719 8,000 84% 8,524$ 5,400 2,600 $1,706 $ 8,600 1% Couriers/Delivery 2,588 1,315 3,000 44% 2,886$ 3,000 $ 3,000 4% Depreciation 12,504 10,335 13,700 75% 12,116$ 13,700 $ 11,802 -3% Insurance 7,309 7,082 7,200 98% 7,082$ 7,200 $ 7,200 2% Office Expense Office Supplies 12,507 11,109 19,300 58% 14,589$ 19,300 $ 14,000 -4% Office Equip./Furn. 2,471 11,879 9,000 132% 11,910$ 9,000 $ 9,000 -24% Office subscriptions 5,022 5,779 5,000 116% 6,821$ 5,000 $ 6,200 -9% Stationery 4,476 2,424 1,000 242% 2,424$ 1,000 $ 2,500 3% Postage 2,569 2,455 5,000 49% 3,850$ 5,000 $ 5,000 30% Rent 96,096 98,767 108,000 91% 107,301$ 108,000 $ 110,550 3% Telephone 19,049 13,489 17,500 77% 13,962$ 17,500 $ 16,500 18% Total Office Expenses 171,574 171,354 196,700 87% 191,465 194,100 2,600 1,706 194,352 2%
Professional Fees: Accounting 55,420 52,715 52,000 101% 57,000$ 52,000 $ 55,000 -4% Audit 12,200 12,585 12,500 101% 12,585$ 12,500 $ 12,600 0% Communications - Consulting 48,693 40,968 61,500 67% 72,074$ 51,500 10,000 $21,700 $ 130,000 80% Communications - Printing 22,494 10,302 32,300 32% 30,746$ 19,300 13,000 $8,247 $ 45,000 46% General Consulting Fees 41,857 63,212 58,500 108% 76,109$ 21,100 37,400 $44,844 $ 90,000 18% Policy - Consulting 82,268 2,756 100,000 3% 2,756$ 100,000 $ 116,000 4109% Deferred Compensation 150,049 175,243 195,000 90% 175,243$ 195,000 $ 169,825 -3% IT Network Support 32,157 26,546 35,500 75% 33,127$ 35,500 $ 60,000 81% Legal 1,416 408 1,000 41% 408$ 1,000 $ 1,000 145% Payroll 1,093,857 1,069,176 1,285,000 83% 1,233,189$ 1,285,000 $ 1,247,000 1% Total Professional Fees 1,540,412 1,453,910 1,833,300 79% 1,693,237 1,772,900 60,400 74,791 1,926,425 14%
Education: Board Meetings 6,082 5,040 5,300 95% 7,000$ 5,300 $ 7,900 13% Committee Meetings 7,497 6,205 9,500 65% 8,054$ 9,500 $ 9,500 18% Events 87,879 60,278 200,000 30% 269,160$ 18,000 182,000 $173,874$ 255,562 -5% Total Education Expenses 101,457 71,522 214,800 33% 284,214 32,800 182,000 173,874 $ 272,962 -4%
Special Projects: Dx Value Project 3,836 13,753 81,284$ $ 200,000 146% Education Initative EU Landscape Analysis PM Integration Case Study 3,448 5,448$ Total Special Project Expense 3,836 17,202 86,732 $ 200,000 131%
Business Development: 0 Membership Development 48,606 27,771 70,000 40% 50,398$ 55,000 15,000 $10,612 $ 70,000 39% Sponsorship/Membership 21,900 1,900 2,000 95% 1,900$ 2,000 $ 2,000 5% Total Bus. Development Expenses 70,506 29,671 72,000 41% 52,298 57,000 15,000 10,612 $ 72,000 38%
Total Expenses 1,887,786 1,743,659 2,316,800 75% 2,307,946 2,056,800 260,000 $260,983 2,665,739 16% Increase to Net Assets $ 232,640 244,545$ 3,200$ 997$ $ (66,800) 70,000$ $185,775 $ 761 -24%
Finance and Budget | p. 1
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Finance and Budget | p. 2 PMC Historical Budget Nov 10, 2016
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Actual Actual Actual Actual Actual Actual Actual Actual Final Final Revenue: Membership Dues Invoiced 355,625 521,500 593,375 813,750 1,014,500 1,221,250 $ 1,512,420 $ 1,528,700 $ 1,552,966 $ 1,654,050 Non-Renewing Member Dues 0 0 -100,500 -108,500 (204,750) (191,400) (209,250) (154,000) Membership Dues Outstanding 0 0 Membership-Deferrals -20,000 Renewing Member Dues-Net 355,625 521,500 593,375 813,750 914,000 1,092,750 1,307,670 1,337,300 1,343,716 1,500,050
Admission Fees Non-Members 2,245 3,576 13,625 1,375 19,691 1,410 26,389 3,752 22,092 8,994 Friends of the PMC 0 0 0 0 125,000 85,000 65,000 60,000 45,000 57,166 Honoraria/Miscellaneous 0 0 0 1,100 5,750 9,500 6,432 1,310 10,317 4,953 Sponsorship 112,000 78,000 25,230 267,500 128,750 85,000 175,000 249,500 396,500 421,000 Special Projects 0 111,000 260,770 Current 104,500 392,458 142,500 0 Deferred 86,042 118,000 29,500 Interest Earned 4,466 11,739 15,374 7,186 11,004 2,864 1,440 6,932 3,515 8,104 Total Revenue 474,336 725,815 908,374 1,195,411 1,682,695 1,537,024 1,611,431 1,658,794 1,821,140 2,000,266
Expenses: Office Expenses: Bank Charges 57 20 30 162 523 308 1,938 1,431 2,377 5,301 Couriers/Delivery 647 1,105 1,439 338 387 722 531 1,527 5,835 2,697 Depreciation 555 642 1,032 1,639 2,485 2,380 2,858 3,249 11,204 13,078 Insurance 1,895 3,891 3,947 3,978 4,466 4,161 3,703 5,423 6,423 7,090 E.A. Relocation Expenses 24,886 7,000 Office Expense Office Supplies 2,926 3,733 7,121 6,684 9,433 9,287 8,951 6,983 13,703 12,574 Office Equip./Furn. 1,432 2,635 1,909 5,789 1,585 1,353 6,988 1,635 59,847 11,564 Office subscriptions 0 0 0 2,723 2,722 3,434 4,544 3,552 3,710 5,299 Stationary 0 0 683 1,547 1,121 1,296 5,461 382 Postage 72 803 1,439 1,637 2,389 2,850 2,820 2,712 2,995 4,615 Rent 0 4,000 49,000 55,361 80,025 94,114 91,620 95,400 98,691 102,094 Telephone 4,964 6,352 7,160 6,345 10,224 11,404 11,313 14,115 15,762 17,901 Total Office Expenses 12,548 23,181 73,077 84,656 114,921 131,560 136,387 137,323 250,894 189,595
Professional Fees: Accounting 22,342 18,835 15,341 17,156 28,857 31,196 39,182 43,143 55,765 55,728 Audit 0 5,900 5,900 6,000 6,000 6,000 6,000 11,180 11,590 11,836 Communications -Consulting 121,876 168,928 177,340 106,217 110,243 115,313 48,726 48,901 65,419 186,434 Communications -Printing 15,039 19,285 7,193 9,243 7,021 13,485 9,820 13,194 20,105 27,582 Consulting Fees 5,057 0 2,500 28,329 90,627 59,844 22,941 116,993 256,105 35,372 Policy-Consulting n/a n/a n/a n/a n/a n/a n/a n/a n/a 65,098 Deferred Compensation 87,000 38,600 21,595 113,550 70,932 88,016 98,856 91,532 85,664 44,974 IT Network Support 2,846 1,664 2,000 22,558 16,374 10,406 24,259 17,069 39,822 49,582 Legal 0 0 15,994 481 1,630 1,366 711 7,072 108 Payroll 125,145 200,287 294,507 400,749 567,238 614,196 710,167 803,897 870,246 1,082,212 Total Professional Fees 379,305 453,499 542,370 704,283 898,922 939,822 960,662 1,152,981 1,404,823 1,558,818
Education: Board Meetings 0 0 0 19,904 2,196 4,486 4,931 7,066 5,053 5,298 Committee Meetings 0 0 0 3,785 4,591 3,365 1,124 5,921 4,278 6,423 Events 37,888 23,376 21,008 3,033 18,050 70,543 69,752 135,122 81,931 92,528 Rghts & Reproductions 4,381 0 0 0 0 Total Education Expenses 42,269 23,376 21,008 26,722 24,837 78,394 75,807 148,109 91,262 104,248
Business Development: Membership Development 29,428 24,537 31,115 30,114 27,888 24,227 42,056 49,417 50,751 53,017 Sponsorship/Membership 0 0 535 11,090 10,700 11,385 23,654 21,845 22,704 21,800 Total Bus. Development Expenses 29,428 24,537 31,650 41,204 38,588 35,612 65,710 71,262 73,455 74,817
Total Expenses 463,550 635,593 928,875 973,107 1,469,725 1,401,542 1,289,788 1,509,675 1,820,434 1,927,478
Increase/(Decrease) to Net Assets 10,786$ 90,732$ $ (20,501) 222,304$ $ 212,970 135,482$ $ 321,643 $ 149,119 $ 706 72,788
Finance and Budget | p. 3
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Finance and Budget | p. 4 PERSONALIZED MEDICINE COALITION
2016 Sponsorship - Nov 10, 2016 Name Invoiced Paid Restriction, if any ACLA $ 1,000 $ 1,000 SOPM Agios $ 5,000 $ 5,000 Annual Conference Astellas $ 25,000 $ 25,000 Annual Conference AstraZeneca $ 5,000 $ 5,000 Annual Conference Bristol-Myers Squibb Company $ 15,000 $ 15,000 Annual Conference Caris $ 20,000 $ 20,000 Value Project Catholic Health Initiative Dignity Health - Precision Medicine Alliance $ 15,000 Annual Conference Change Healthcare (formerly Emdeon) $ 5,000 Annual Conference Endo $ 10,000 $ 10,000 Annual Conference Feinstein Kean Healthcare $ 1,000 $ 1,000 SOPM Feinstein Kean Healthcare $ 5,000 Annual Conference FlatironHealth $ 15,000 Annual Conference Foley & Lardner LLP $ 10,000 $ 10,000 Annual Conference Foundation Med $ 15,000 $ 15,000 Annual Conference Foundation Med $ 25,000 Value Project Genentech $ 17,500 $ 17,500 Annual Conference Genomic Health $ 5,000 $ 5,000 Annual Conference Greybird $ 5,000 $ 5,000 Annual Conference Illumina $ 20,000 Value Project Inivata $ 3,150 $ 3,150 Annual Conference Intermountain $ 35,000 $ 35,000 Annual Conference Invivoscribe $ 10,000 $ 10,000 Annual Conference Johnson & Johnson $ 30,000 $ 30,000 SOPM LabCorp $ 10,000 Value Project Leerink Partners $ 5,000 $ 5,000 Annual Conference LEK Consulting $ 10,000 $ 10,000 Annual Conference M2Gen $ 1,000 $ 1,000 Annual Conference Molecular Health $ 10,000 $ 10,000 Annual Conference N-of-one $ 10,000 $ 10,000 Value Project N-of-one $ 5,000 $ 5,000 Case Study Project (60/40 split) Nanostring $ 10,000 $ 10,000 Annual Conference National Foundation for Cancer Annual Conference Research $ 5,000 $ 5,000 Nat'l Pharma Council $ 1,000 $ 1,000 SOPM Nat'l Pharma Council $ 5,000 $ 5,000 Annual Conference Nixon Peabody $ 5,000 $ 5,000 Annual Conference Oracle Health Sciences $ 15,000 $ 15,000 Annual Conference Pfizer $ 15,000 $ 15,000 Annual Conference Pfizer $ 25,000 Value Project PhRMA $ 50,000 $ 50,000 Unrestricted PhRMA $ 75,000 $ 75,000 Unrestricted Qiagen $ 25,000 Value Project Roche $ 17,500 $ 17,500 Annual Conference Seven Bridges $ 15,000 Annual Conference Slone Partners $ 10,000 $ 10,000 Annual Conference ThermoFish $ 25,000 Value Project Third Rock $ 5,000 $ 5,000 Annual Conference UC Davis $ 1,000 $ 1,000 Annual Conference Vertex $ 10,000 Annual Conference TOTAL $ 663,150 $ 468,150 OUTSTANDING $ 195,000
Finance and Budget | p. 5
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Finance and Budget | p. 6 PERSONALIZED MEDICINE COALITION
2016 Friends of the PMC -Nov 10, 2016
Amount Invoiced 2016 Paid Mark Levin $ 20,000 $ 20,000 Rajuu K. $ 10,000 $ 10,000
TOTAL $ 30,000 $ 30,000
Finance and Budget | p. 7
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Finance and Budget | p. 8 PERSONALIZED MEDICINE COALITION
Cash and Investments 11/10/16
2015 Investments
Amount Year-to-date Return
T. Rowe Price Acct Spectrum Income $ 662,478 8.68% 52905.11 Ultra Short-Term Bond $ 317,044 1.77% 5503.75
T Rowe Price Total $ 979,522 6.34% 58408.86
Sun Trust Money Market # 29620 $ 315,061 0.04% 116.25
Total Investments $ 1,294,584
Checking/Cash Suntrust $ 308,099
Cash and Investments @ 11/10/16 $ 1,602,683
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Finance and Budget | p. 10 Finance and Budget | p. 11
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Finance and Budget | p. 12 Finance and Budget | p. 13
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Finance and Budget | p. 16 Finance and Budget | p. 17
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Finance and Budget | p. 18
6. Membership
Membership | p. 1
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Membership | p. 2 2016 Membership and Sponsorship Dues Schedule as of December 7, 2016 Date. Contact Name Company Invoiced 2016 Paid 2016 Year
Membership Dues Sponsorship Membership Dues Sponsorship √ = new 1 12/3/15 Anne Wojcicki 23&Me $ 5,250 $ 5,250 2 12/3/15 Brent Gendleman 5AM Solutions $ 3,150 $ 3,150 3 12/3/15 Kathryn Becker Abbott $ 39,375 $ 39,375 4 12/3/15 Liz Hanpeter AbbVie $ 26,250 $ - NR 5 12/3/15 Robert McBurney Accelerated Cure Project for Multiple Sclerosis $ 525 $ 525 6 12/3/15 Melina Cimler Adaptive Biotechnologies $ 3,150 7 12/3/15 Advanced Individual Medicine LLC $ 3,150 $ - NR 8 12/16/15 Daniel Knecht Aetna $ 23,000 $ 23,000 Christa Kerkorian Agios sponsorship only$ 5,000 $ - $ 5,000 9 12/3/15 Bas van der Baan Agendia NV $ 5,250 $ 5,250 10 12/3/15 Bodo Lange Alacris Theranostics GmbH $ 3,150 $ 3,150 11 12/3/15 Cynthia Bens Alliance for Aging Research $ 525 $ 525 12 12/3/15 Karen Keating Almac Diagnostics $ 5,250 $ 5,250 13 12/3/15 Dr. Hani El Shawa AlphaGenomix Laboratories $ 3,150 $ 3,150 14 1/13/16 Stafford O'Kelly Altan Pharma Ltd. $ 1,575 $ 1,575 2016 15 12/3/15 Greg Hamilton AltheaDX $ 3,150 $ 3,150 16 12/3/15 Jon Retzlaff American Association for Cancer Research $ 5,250 $ 5,250 17 12/3/15 Alan Mertz American Clinical Laboratory Association $ 6,825 $ 1,000 $ 6,825 $ 1,000 18 12/3/15 Katie Johansen Taber American Medical Association $ 5,250 $ 5,250 19 12/3/15 Sasha Kamb/John Laubacher Amgen, Inc. $ 26,250 $ 26,250 20 8/1/16 Mary Del Brady Ariel Precision Medicine $ 1,000 $ 1,000 2016 21 12/3/15 Jen Madsen Arnold & Porter LLP $ 2,625 $ 2,625 22 12/3/15 John Waslif Arrowhead $ 2,625 $ - NR 23 12/3/15 Mary Steele Williams Association for Molecular Pathology (AMP) $ 2,625 $ 2,625 24 12/3/15 James Burns Assurex Health, Inc. $ 5,250 $ 5,250 25 12/3/15 Stephen L. Eck/Mary Lacey Astellas Pharma US, Inc. $ 39,375 $ 25,000 $ 39,375 $ 25,000 26 12/3/15 Ray Parisi AstraZeneca $ 26,250 $ 5,000 $ 26,250 $ 5,000 27 12/3/15 Matt McManus ASURAGEN, Inc. $ 5,250 $ 5,250 28 12/3/15 Todd Rothenhaus athenahealth $ 13,125 $ - NR 29 12/3/15 Adam Borden Avalere $ 2,625 $ 2,625 30 9/9/16 Suku Nagendran AveXis $ 5,250 $ 5,250 2016 31 12/3/15 Jasmina Koeva BAPEMED $ 525 $ 525 32 12/3/15 Bob Mennel Baylor Health Care System Precision Medicine Institute$ 2,625 $ 2,625 33 12/3/15 Jenny Luray BD (Becton Dickinson & Co.) $ 26,250 $ 26,250 Genome magazine (formerly Big Science 34 12/3/15 Susan McClure Media) $ 2,625 $ 2,625 35 12/3/15 Phyllis Arthur BIO (Biotechnology Innovation Organization) $ 15,000 $ 15,000 36 6/13/16 Laure Fabrega BIOCOM $ 2,625 $ 2,625 2016 37 12/3/15 Rachel Berry Biodesix $ 5,250 $ - NR 38 1/7/16 Paul Billings Biological Dynamics, Inc. $ 4,000 $ 4,000 2016 39 12/3/15 Joachim Greuel Bioscience Valuation BSV GmbH $ 2,625 $ 2,625 40 12/3/15 Stacie Phan Boehringer-Ingleheim Pharmaceuticals, Inc. $ 26,250 $ 26,250 41 12/3/15 Bonnie Addario Bonnie J. Addario Lung Cancer Foundation $ 525 $ 525 42 12/3/15 Evian Gordon, M.D. Brain Resource Company Limited $ 3,150 Brigham and Women’s Hospital, 43 6/17/15 Robert Green Genomes2People Research Program $ 2,625 $ 2,625 2016 44 12/3/15 Steve D. Averbuch, M.D. Bristol-Myers Squibb Company $ 39,375 $ 15,000 $ 39,375 $ 15,000 45 12/3/15 Edward Hawrot, Ph..D. Brown University $ 2,625 $ 2,625 46 Suri Harris CAHG $ - NR 47 12/3/15 Phillips Kuhl Cambridge Healthtech Institute $ 2,625 $ 2,625 48 12/3/15 Marty Tenenbaum Cancer Commons $ 525 $ - NR 49 12/3/15 Susan Zook Cancer Treatment Centers of America $ 5,250 $ 5,250 50 12/3/15 Martin LeBlanc/Carol Berry Caprion Proteomics $ 5,250 $ 5,250 51 12/3/15 Vernon Holt Carcinoid-NeuroEndocrine Tumour Society-Canada$ 525 $ - NR 52 12/3/15 Peter Maag, Ph.D. CareDx $ 13,125 $ 13,125 53 12/3/15 Scott Boyle Caris Life Sciences $ 5,250 $ 20,000 $ 5,250 $ 20,000 54 12/3/15 Damon Hostin Catholic Health Initiative Precision Medicine $ 2,625 $ 15,000 $ 2,625 55 1/17/16 Cintia Vilhena Centro de Genomas $ 5,250 2016 56 12/3/15 Neil de Crescenzo Change Healthcare (formerly Emdeon) $ 39,375 $ 5,000 $ 39,375 $ 5,000 57 10/25/15 Christof Koelsch CKSA $ 1,050 $ 1,050 2016 58 2/24/16 Peter Hurwitz Clarity LLC $ 2,625 $ 2,625 2016 59 12/3/15 Heather Fehling, Ph.D. Clinical Reference Laboratory, Inc. $ 5,250 $ 5,250 60 12/3/15 Mark Trusheim Co-Bio Consulting, LLC $ 1,050 $ 1,050 61 12/3/15 John Scott College of American Pathologists $ 15,000 $ 15,000 62 12/3/15 Margie Sherlock ConText $ 1,050 $ 1,050 63 12/3/15 Brett Davis ConvergeHEALTH by Deloitte $ 2,625 $ 2,625 64 12/3/15 Michael Christman, Ph.D. Coriell Institute for Medical Research $ 2,625 $ 2,625 65 12/3/15 Ted Snelgrove Counsyl $ 5,250 $ 5,250 66 12/3/15 Carl Borrebaeck, Ph.D. CREATE Health Translational Cancer Centre $ 2,625 $ 2,625 67 12/3/15 Vamil Divan, M.D. Credit Suisse $ 2,625 $ 2,625 68 12/3/15 Martin Naley Cure Forward $ 3,150 $ 3,150 69 12/3/15 Andre de Fusco Cynvenio Biosystems, Inc. $ 3,150 $ 3,150 70 12/3/15 Thomas Klein Cytolon AG/Be The Partner LLC $ 3,150 $ 3,150 71 12/3/15 Edward C. Saltzman Defined Health $ 2,625 $ 2,625 72 12/3/15 Cindy MacCullough DNA Genotek Inc. $ 3,150 $ 3,150
Membership | p. 3 Date. Contact Name Company Invoiced 2016 Paid 2016 Year
Membership Dues Sponsorship Membership Dues Sponsorship √ = new 73 12/3/15 Angela Anderson DNAnexus $ 3,150 $ 3,150 74 12/3/15 Cynthia LaConte Dohmen Life Science Services $ 5,250 $ - NR 75 12/3/15 Ralph Synderman Duke University $ 2,625 $ 2,625 76 12/3/15 Dr. Richard Janeczko Dx Economix Inc. $ 1,050 $ - NR 77 12/3/15 Qin Shi, J.D., Ph.D. Edgetech Law LLP $ 2,625 $ 2,625 78 12/3/15 Timothy Garnett Eli Lilly and Company $ 39,375 $ 39,375 79 12/3/15 Chris Mancill EMD Serono, Inc. $ 26,250 $ 26,250 80 2/10/16 Anthony Johnson Empire Genomics, LLC $ 3,150 $ 3,150 2016 81 10/29/15 J. Brian Munroe Endo Health Solutions $ 20,000 $ 10,000 $ 20,000 $ 10,000 82 12/3/15 Murali Prahalad, Ph.D. Epic Sciences $ 3,150 $ - NR 83 12/3/15 Glen Giovannetti/Kristin PothierErnst & Young Global Life Sciences Center $ 2,625 $ 2,625 84 1/7/16 Richard Ziegler Essentia Institute of Rural Health $ 2,625 $ 2,625 85 12/3/15 Kevin Conroy Exact Sciences $ 13,125 $ - NR 86 12/3/15 Tom McLean Exosome Diagnostics $ 3,150 $ 3,150 87 Expression Analysis $ - $ - NR 88 3/14/16 Bruce Quinn FaegreBD $ 2,625 $ 2,625 2016 89 12/3/15 Margaret Anderson FasterCures $ 2,625 $ - NR 90 12/3/15 Marcia Kean Feinstein Kean Healthcare $ 2,625 $ 6,000 $ 2,625 $ 6,000 91 12/3/15 Amy Abernethy Flatiron Health $ 7,875 $ 15,000 $ 7,875 2016 92 12/3/15 Rouget Henschel/ Mayumi WillieFoley & Lardner LLP $ 2,625 $ 10,000 $ 2,625 $ 10,000 93 12/3/15 Hathaway Russell/Brian Carey Foley Hoag LLP $ 2,625 $ 2,625 94 12/3/15 Mike Pellini Foundation Medicine, Inc. $ 20,000 $ 40,000 $ 20,000 $ 15,000 95 12/3/15 Jeff Allen/ Berrett Friends of Cancer Research $ 525 $ 525 96 12/3/15 Trevor Hawkins GE Healthcare $ 26,250 $ - NR 97 12/3/15 Myla Lai-Goldman GeneCentric Diagnostics, Inc. $ 3,150 $ 3,150 98 8/22/16 Vanessa Gannon Genentech $ 26,250 $ 17,500 $ 26,250 $ 17,500 99 12/3/15 Stefan Roever Genia Technologies $ 3,150 $ 3,150 100 12/3/15 Catalina Lopez Correa Genome British Columbia $ 2,625 $ 2,625 101 12/3/15 Andrea Matyas Genome Canada $ 2,625 $ 2,625 102 12/3/15 Marc LePage Génome Québec $ 2,625 $ 2,625 103 12/3/15 Kim Popovits Genomic Health, Inc. $ 26,250 $ 5,000 $ 26,250 $ 5,000 104 12/3/15 Ronald Dozoretz Genomind, LLC $ 3,150 $ - NR 105 12/3/15 Daniel Meyer GenoSpace $ 3,150 $ 3,150 106 1/7/16 Gavin Erickson GfK $ 2,625 $ - NR 107 12/3/15 Marielena Mata, PhD (Maty) GlaxoSmithKline $ 26,250 $ 26,250 108 9/26/16 Sean Hu GlobalData PLC $ 2,625 $ 2,625 2016 109 12/3/15 Donna Cryer Global Liver Institute $ 785 $ 785 110 11/24/15 Colin Hill GNS Healthcare $ 3,150 $ 3,150 2016 111 12/3/15 Sheila Walcoff Goldbug Strategies $ 1,050 $ 1,050 112 12/3/15 Tom Miller GreyBird $ 2,625 $ 5,000 $ 2,625 $ 5,000 113 12/3/15 Matt Turner Hanson Wade $ 2,625 $ - NR 114 9/15/16 Michael Sherman Harvard Pilgrim Health Care $ 5,250 $ 5,250 2016 115 3/4/16 Richard Hamermesh Harvard Business School $ 2,625 $ 2,625 2016 116 12/3/15 Gary Gustavsen Health Advances, LLC $ 2,625 $ 2,625 2016 117 11/11/15 Stephen DeCherney Health Decisions $ 5,250 $ 5,250 2016 118 12/3/15 Jennifer Leib HealthFutures, LLC $ 2,625 $ 2,625 119 7/25/16 Tamar Thompson Healthy Women $ 525 120 12/3/15 Corinna Barz Helmholtz Zentrum München $ 2,625 $ 2,625 121 12/3/15 Helomics $ 3,150 122 12/3/15 Jonathan S. Kahan Hogan Lovells, LLP $ 2,625 $ 2,625 123 7/22/16 Sally Howard Human Longevity $ 5,250 124 12/3/15 Jay Flatley Illumina, Inc. $ 26,250 $ 20,000 $ 26,250 125 12/3/15 Albert A. Luderer, Ph.D. Indi - Integrated Diagnostics $ 3,150 126 12/3/15 Zeruesenay Desta, Ph.D. Indiana Institute of Personalized Medicine $ 2,625 $ 2,625 127 12/3/15 David Nixon InformedDNA $ 3,150 $ 3,150 128 4/22/16 Michael Stocum Inivata $ 3,150 $ 3,150 $ 3,150 $ 3,150 2016 129 12/3/15 Marshall Ruffin, M.D. Inova Health System $ 2,625 $ 2,625 130 12/3/15 Amir Lewkowicz Inspire $ 2,500 $ 2,500 Institute for Translational Oncology Research 131 12/3/15 Jeffery Edenfield (ITOR) $ 2,625 $ - NR 132 4/29/16 Jesus Fernandez Crespo Instituto de Salud Carlos III $ 2,625 133 12/3/15 Alice Borrelli Intel $ 26,250 $ 26,250 134 12/3/15 Kenneth Kornman Interleukin Genetics Inc. $ 3,150 $ 3,150 135 6/29/16 Jason Gillman/Tazia Taylor Intermountain Healthcare $ 2,625 $ 35,000 $ 2,625 $ 35,000 International Cancer Advocacy Network 136 12/3/15 Marcia Horn, Esq. ("ICAN") $ 50 $ 50
137 12/3/15 Hiroyuki ABE, MD International Society of Personalized Medicine $ 2,625 $ 2,625 138 12/3/15 Russell Ingersoll Intervention Insights $ 3,150 $ 3,150 139 11/10/15 Jeff Miller Invivoscribe $ 5,250 $ 10,000 $ 5,250 $ 10,000 2016 140 12/3/15 Mike Hyde Jackson Laboratory $ 2,625 $ 2,625 141 12/3/15 Jared Schwartz Jared N Schwartz MD, PhD LLC $ 1,575 $ 1,575 142 12/3/15 Andrea Masciale Johnson & Johnson $ 26,250 $ 30,000 $ 26,250 $ 30,000 143 12/3/15 Tuan Ha-Ngoc KEW Group $ 3,150 $ 3,150 144 12/3/15 DennyVan Liew Kinapse $ 2,625 $ 2,625 145 12/3/15 David M. Fineman KineMed, Inc. $ 3,150 $ - NR 146 12/3/15 Brook Byers Kleiner, Perkins, Caufield & Byers $ 2,625 $ 2,625
Membership | p. 4 Date. Contact Name Company Invoiced 2016 Paid 2016 Year
Membership Dues Sponsorship Membership Dues Sponsorship √ = new 12/3/15 Joseph Carroll Knight Cancer Institute - OHSU $ 2,625 $ 2,625 147 Jamie Aframe Leerink Partners sponsorship only$ 5,000 $ - $ 5,000 148 12/3/15 Sue St. Sure L.E.K. Consulting $ 2,625 $ 10,000 $ 2,625 $ 10,000 Laboratory Corporation of America Holdings 149 12/3/15 David King (LabCorp) $ 39,375 $ 10,000 $ 39,375 150 12/3/15 Jonathan Roy Leica $ 39,375 $ - NR 151 12/3/15 Homi Shamir Luminex Corporation $ 13,125 $ 13,125 152 12/3/15 Andrea Ferris LUNGevity Foundation $ 525 $ 525 153 12/3/15 William S. Dalton, Ph.D., MD M2Gen $ 3,950 $ 1,000 $ 3,950 $ 1,000 154 12/3/15 David Kisor Manchester University School of Pharmacy $ 2,625 $ 2,625 155 12/3/15 Brian Lester Manning & Napier Advisors LLC $ 2,625 $ - NR 156 8/6/16 Selin Kurnaz, PhD Massive Bio, Inc. $ 3,150 $ 3,150 2016 157 12/3/15 Murray Brilliant Marshfield Clinic $ 2,625 $ 2,625 158 12/3/15 Keith Stewart, M.B., Ch.B Mayo Clinic $ 2,625 $ 2,625 159 12/3/15 Paul Radensky McDermott Will & Emery LLP $ 2,625 $ 2,625 160 1/13/16 Matt Zubiller McKesson Health Solutions $ 6,250 $ 6,250 161 9/16/16 Kenna Shaw MD Anderson $ 2,625 162 12/17/15 Randy Marsh Melanoma Research Alliance Foundation $ 525 $ 525 163 10/26/16 Erin Darling Merck $ 26,250 $ 26,250 2016 164 12/3/15 Shaun Lonergan Metabolon, Inc $ 3,150 $ 3,150 165 12/3/15 John Troup Metagenics, Inc $ 5,250 $ - NR 166 12/3/15 Jerry Williamson Metamark Genetics $ 3,150 $ 3,150 167 12/3/15 Michael J. Bauer, M.D. Michael J. Bauer, MD & Associates, Inc. $ 1,050 $ 1,050 168 12/3/15 Ronald Rittenmeyer Millennium Health $ 5,250 $ - NR 169 12/3/15 Lynn Dressler Mission Health, Fullerton Genetics Center $ 2,625 $ 2,625 170 12/3/15 Howard McLeod, PharmD Moffitt Cancer Center $ 3,950 $ 3,950 171 12/3/15 Phyllis E. Whiteley, Ph.D. Mohr Davidow $ 2,625 $ 2,625 172 12/3/15 Les Paul Molecular Health $ 3,150 $ 10,000 $ 3,150 $ 10,000 173 12/3/15 Kevin Coker MolecularMatch $ 3,150 174 12/3/15 Dan Snyder MolecularMD $ 5,250 175 12/3/15 Walter Capone/Kathy Giusti Multiple Myeloma Research Foundation $ 525 $ 525 176 12/3/15 Jennifer Carter, M.D., M.P.H. N-of-One $ 3,150 $ 15,000 $ 3,150 $ 15,000 177 12/3/15 Brad Gray NanoString Technologies $ 13,125 $ 10,000 $ 13,125 $ 10,000 178 12/3/15 Gary Palmer NantHealth (formerly under NantOmics) $ 5,250 $ 5,250 179 12/3/15 Jane L. Delgado National Alliance for Hispanic Health $ 525 $ 525 180 12/3/15 Kris Knight/Sally Davis National Brain Tumor Society $ 525 $ - NR 181 12/3/15 Franklin C. Salisbury, Jr. National Foundation for Cancer Research $ 2,625 $ 5,000 $ 2,625 $ 5,000 182 12/3/15 Alan Balch National Patient Advocate Foundation $ 525 $ 525 183 12/3/15 Dan Leonard National Pharmecutical Council $ 5,250 $ 6,000 $ 5,250 $ 6,000 184 7/28/16 Jeff Gross Navigant $ 2,625 $ 2,625 2016 185 12/3/15 Gillian Hooker NextGxDx $ 3,150 $ 3,150 186 12/3/15 David Resnick/Karen Nevins Nixon Peabody LLP $ 2,625 $ 5,000 $ 2,625 $ 5,000 187 7/25/16 Peter Hulick NorthShore University HealthSystem $ 2,625 $ 2,625 188 12/3/15 Steve Rosen Novartis Pharmaceuticals $ 26,250 $ 26,250 189 12/3/15 Jianfu Wang Novodiax Inc $ 3,150 $ - NR 190 12/3/15 Todd Hembrough OncoPlex Diagnostics $ 3,150 $ - NR 191 3/17/16 Sam Prince One Disease at a Time $ 525 192 12/3/15 Mark Poznansky Ontario Genomics $ 2,625 $ 2,625 193 12/3/15 Deanna Darlington Onyx Pharmaceuticals $ 13,125 $ - NR 194 12/3/15 Jonathan Sheldon/Clare Gaul Oracle Health Sciences $ 26,250 $ 15,000 $ 26,250 $ 15,000 195 12/3/15 Dr. Scott Weiss Partners HealthCare Personalized Medicine $ 2,625 $ 2,625 196 12/3/15 Alan Campbell PCLS $ 5,250 $ - NR 197 12/3/15 Mary Pendergast Pendergast Consulting $ 1,050 $ 1,050 198 12/3/15 Melody Gretz Personal Genome Diagnostics (PGDx) $ 3,150 $ 3,150 199 12/3/15 Brian Tyburski Personalized Medicine in Oncology $ 2,625 $ 2,625 200 12/3/15 Michael Stocum Personalized Medicine Partners, LLC $ 1,050 $ - NR 201 12/3/15 Dendy Young/Doug Perthera $ 3,150 $ 3,150 202 12/3/15 Safiyya Dharssi Pfizer Inc. $ 19,687.50 $ 12,500 $ 19,687.50 $ 12,500 203 12/3/15 Hakan Sakul Pfizer Inc. $ 19,687.50 $ 27,500 $ 19,687.50 $ 27,500 204 12/3/15 Lori M. Reilly, Esq. PhRMA $ 39,375 $ 125,000 $ 39,375 $ 125,000 205 Tal Behar PMWC Intl $ 2,625 206 12/3/15 Paola Belloni Poliambulatorio Euganea Medica $ 2,625 $ 2,625 207 12/3/15 David Parker Precision for Value (Formerly Precision for Medicine)$ 5,250 208 12/7/15 Ian Wright Precision Health Initiative at Cedars-Sinai $ 2,625 $ 2,625 2016 209 12/3/15 Gerry McDougall PricewaterhouseCoopers LLP $ 2,625 $ 2,625 210 12/3/15 Carolyn Farrell Professional Genetic Interactions $ 1,050 $ 1,050 211 12/3/15 Brian Meshkin Proove Biosciences $ 3,150 $ 3,150 212 12/3/15 Nahla Afifi Qatar Biobank $ 2,625 $ 2,625 QIAGEN, Inc. (formerly QIAGEN Manchester 213 12/3/15 Lena Chaihorsky Ltd) $ 13,125 $ 25,000 $ 13,125 214 12/3/15 Daniel Bouthillier Quebec Network for Personalized Health Care $ 2,625 $ 2,625 215 12/3/15 J.G. Wohlgemuth, M.D. Quest Diagnostics $ 39,375 $ 39,375 216 12/3/15 Jacqueline Huang Quorum Consulting $ 2,625 $ 2,625 Raabe College of Pharmacy, Ohio Northern 217 1/26/16 Yousif Rojeab University $ 500 $ 500 2016 218 12/3/15 Mikio Kawahara RIKEN GENESIS $ 3,150 $ 3,150
Membership | p. 5 Date. Contact Name Company Invoiced 2016 Paid 2016 Year
Membership Dues Sponsorship Membership Dues Sponsorship √ = new 219 9/8/16 Kate Claessens Roche Diagnostics $ 26,250 $ 17,500 $ 26,250 $ 17,500 220 12/3/15 Carl Morrison Roswell Park Cancer Institute $ 2,625 $ 2,625 221 Russell Reynolds $ - $ - NR 222 12/3/15 Lorna Rodriguez Rutgers Cancer Institute of New Jersey $ 2,625 $ 2,625 223 12/3/15 E. Eugene Hoyme, M.D. Sanford Imagenetics, Sanford Health $ 2,625 $ 2,625 224 12/3/15 Seegene Technologies $ 3,150 $ - NR 225 11/25/15 Andrew Gruen Seven Bridges $ 5,250 $ 15,000 $ 5,250 2016 226 12/3/15 Fernando Beils Siemens Healthcare Diagnostics $ 26,500 $ 26,500 227 12/3/15 Tara Kochis-Stach Slone Partners $ 2,625 $ 10,000 $ 2,625 $ 10,000 228 12/3/15 Byron Hewett SomaLogic $ 5,250 $ 5,250 229 12/3/15 John Wilson Spectrum $ 2,625 $ 2,625 230 12/3/15 Kieran English Spencer Stuart $ 2,625 $ - NR 231 12/3/15 Jason Merker Stanford University School of Medicine $ 2,625 $ 2,625 232 12/3/15 Vikash Neelakantan Strand Genomics, Inc. $ 3,150 $ - NR 233 3/17/16 Jiasen Xu, Ph.D. SurExam $ 3,150 234 12/3/15 Sutter Health $ 2,625 $ 2,625 235 12/3/15 Jonathan Hirsch Syapse $ 3,150 $ 3,150 236 12/3/15 Nancy Simonian Syros Pharmaceuticals $ 3,150 $ 3,150 237 12/3/15 Calvin H. Knowlton Tabula Rasa HealthCare, Inc. $ 5,250 $ 5,250 2016 238 12/3/15 Sal Alesci Takeda Pharmaceutical International Company $ 26,250 $ - NR 239 3/30/16 Thomas Lenk Teal Lion LLC $ 1,050 $ 1,050 2016 240 9/8/16 Ran Kamienchick Teva Pharmaceuticals $ 26,250 $ 26,250 241 12/3/15 Phillip Leming The Christ Hospital $ 2,625 $ 2,625 242 12/3/15 Nigel Russell The Journal of Precision Medicine $ 2,625 $ 2,625 243 12/3/15 Julie Goonewardene The University of Texas System $ 3,950 $ 3,950 244 12/3/15 Tim Fenton Thermo Fisher Scientific $ 26,250 $ 25,000 $ 26,250 245 12/3/15 Mark Levin Third Rock Ventures, LLC $ 2,625 $ 5,000 $ 2,625 $ 5,000 246 12/3/15 Kent Lloyd UC Davis Mouse Biology Program $ 2,625 $ 1,000 $ 2,625 $ 1,000 247 12/3/15 Rick Mandahl UNIConnect, LC $ 3,150 $ 3,150 248 12/3/15 Nita Limdi University of Alabama, Birmingham $ 2,625 $ 2,625 249 12/3/15 Larisa Cavallari University of Florida $ 2,625 $ 2,625 250 12/3/15 David Roth University of Pennsylvania Health System $ 2,625 $ 2,625 251 12/3/15 Steven Shapiro, M.D. University of Pittsburgh Medical Center $ 2,625 $ 2,625 252 9/28/15 Scott Steele University of Rochester $ 2,625 $ 2,625 2016 253 12/3/15 Stephen Liggett University of South Florida Morsani College of Medicine$ 2,625 $ 2,625 254 9/21/16 Michael Vasconcelles, M.D. Unum Therapeutics $ 1,575 $ 1,575 2016 255 12/3/15 Joan Comella Vall d’Hebron Institute of Research (VHIR) $ - $ - 256 12/3/15 Dan M. Roden, M.D. Vanderbilt University Medical Center $ 2,625 $ 2,625 9/29/16 Rachel Radomski Vertex sponsorship only$ 10,000 257 12/3/15 Richard Pollack VCU Health System $ 2,625 $ 2,625 258 12/3/15 Valerie Palmieri Vermillion $ 5,250 $ - NR 259 12/3/15 Duane Schulthess Vital Transformation $ 2,625 $ 2,625 260 9/26/16 Lee Schwartzberg West Cancer Center $ 2,625 $ 2,625 2016 261 9/16/16 Edgar Staren Wake Forest Baptist Medical Center $ 2,625 $ 2,625 2016 262 8/25/16 Greg Vistica Washington Media Group $ 2,625 $ 2,625 2016 263 12/3/15 Lâle White XIFIN, Inc. $ 5,250 $ 5,250 Zinfandel Pharmaceuticals (formerly Cabernet 264 12/3/15 Pharmaceuticals, Inc.) $ 3,150 $ 3,150
Total $ 1,766,060 $ 663,150 $ 1,480,985 $ 503,150 Paid $ (1,480,985) Non-renewing $ (239,400) Outstanding $ 45,675 Percentage of invoiced revenue collected 84% Percentage of budgeted revenue ($1.62M) collected 91%
Date Amout Invoice Amount Collected Percentage 1.15.14 $ 1,653,660 $348,250 21% New Members 34 2.9.15 $1,656,885 $502,600 30% Renewed 179 3.5.15 $1,672,110 $665,675 40% Unpaid 13 4.1.15 $1,649,010 $847,060 51% Non-renewing 37 5.6.15 $1,684,010 $1,056,010 63% Total Members 226 6.1.15 $1,642,550 $1,185,550 72% 7.6.15 $1,729,810 $1,269,660 73% 8.10.15 $1,745,210 $1,367,835 78% 9.1.15 $1,755,185 $1,387,435 79% 10.1.15 $1,778,960 $1,462,510 82% 11.4.15 $1,748,485 $1,487,485 85% 12.31.15 $1,761,610 $1,604,810 91%
Membership | p. 6 Organizations that have withdrawn from PMC 2007 thru December 8, 2016
Year Company Notes Unfortunately, we’re not able to renew our membership this year because of some budget constraints. We do find PMC’s work very 2016 AbbVie valuable, and hope that we’ll be able to be members next year. 2016 Advanced Individual Medicine LLC Lost main contact who subsequent joined under new affiliation No longer promoting their conference without it they did not see the 2016 Arrowhead ROI Unfortunately we have competing priorities amongst society memberships and will need to decline this year’s offer. Please 2016 athenahealth check with us next year. resource contraints, priorities are not going to allow them to extend 2016 Biodesix their membership 2016 CAHG Lost main contact 2016 Cancer Commons doesn't have time to participate I have canvassed our members and all have asked me to cancel our 2016 Carcinoid-NeuroEndocrine Tumour Society-Canada membership in PMC since it is not of particular interest. Following an in-depth review of all of our industry memberships, we decided that the current focus and strategic direction of Dohmen Life Science Services does not align with continuing our PMC 2016 Dohmen Life Science Services membership. 2016 Dx Economix Inc. Did not give a reason 2016 Epic Sciences Did not give a reason 2016 Exact Sciences Lost main contact 2016 Expression Analysis acquired by Q2
As we have been assessing our memberships in various coalitions 2016 FasterCures for 2016, we have decided not to renew our membership with PMC. 2016 GE Healthcare Lost main contact with sale of Clarient While no reflection on PMC, Genomind has decided not to renew our membership this year. We continue to review our organization participation and spending priorities, and will be “heads down” this year with our clinical studies and roll-out of our expanded Genecept Assay™.
We of course will consider renewal for future years, and have 2016 Genomind greatly appreciated the support and information from PMC. As part of our budgeting plan, we analyzed all of our spending on conferences and memberships for 2016. In the final analysis, while we certainly enjoyed our partnership with PMC, we didn’t realize as 2016 GfK much business development opportunities as we had hoped. No longer promoting their conference without it they did not see the 2016 Hanson Wade ROI 2016 Helomics Company has financial issues 2016 Institute for Translational Oncology Research (ITOR) Did not give a reason 2016 KineMed, Inc. Did not give a reason 2016 Leica Acquired by Danaher 2016 Manning & Napier Advisors LLC no longer in the life science group within Manning & Napier 2016 Metagenics, Inc Did not give a reason 2016 Millennium Health Company reorganized lost main contact Lost main contact, and they are currently evaluating their various 2016 National Brain Tumor Society memberships 2016 Novodiax Inc Did not give a reason 2016 OncoPlex Diagnostics Acquired by NantOmics (member under NantHealth) 2016 Onyx Pharmaceuticals acquired by Amgen, now part of Amgen's membership 2016 PCLS acquired by another company 2016 Personalized Medicine Partners, LLC CEO of new company Inivata, which has joined 2016 Russell Reynolds main contact moved to a new firm 2016 Seegene Technologies Did not give a reason 2016 Spencer Stuart Did not give a reason 2016 Strand Genomics, Inc. Lost all US contacts, company based in India 2016 Takeda Pharmaceutical International Company Lost main contact
12/14/16 Membership | p. 7 Organizations that have withdrawn from PMC 2007 thru December 8, 2016
Year Company Notes
After speaking with several internal colleagues, we have determined that we will not continue our membership with PMC at this time. It really came down to a bandwidth issue in getting value out of this. 2016 Vermillion We will re-access routinely and keep you in mind for the future.
Year Company Notes I joined for a very specific reason: to help guide and galvanize support for an industry initiative that a prestigious cancer think tank deemed critical. The PMC science officer that was to be our contact person was not helpful and eventually left the organization. 2015 AcceleratorH In the end, it was not a good use of funds or time. 2015 Atlantic Health System Budgetary constraints 2015 BioStrat Advisory LLC Budgetary constraints 2015 CardioDx, Inc. Budgetary constraints 2015 CBI Did not give a reason 2015 Centro de Genomas Did not participate I regret to inform you that we will not be renewing our membership. I want to clarify that this in no way reflects our perception of the value of the membership, but only a change in the 2015 Cepmed direction and mandate of our organization. Did not have enough time this year to participate but contact again 2015 Clark & Elbing LLP in 2016 2015 Cleveland Clinic Lost main contact, Center for Personalized Healthcare reorganized 2015 Crescendo Bioscience, Inc. Lost main contact, company was acquired by Myriad 2015 Curetis Budgetary constraints The reason why we decided not to renew is mainly because the association doesn’t bring us anything more than what we already 2015 Debiopharm Group have access to. 2015 Diaxonhit Did not participate 2015 Health Advances, LLC Will renew in 2016 2015 Health Synergy Solutions, LLC Did not give a reason Joined to promote their 2014 conference, both contacts 2015 IBC Life Sciences subsequently left IBC 2015 JSB Consulting, LLC Joined a new company which joined PMC 2015 Longview Analytics, LLC Budgetary constraints, no longer on BOD 2015 ML Strategies Lost main contact 2015 Ohio State University Medical Center Lost main contact 2015 Precision Biologics, Inc. Lost main contact 2015 ProDuCt Project Development Consulting JSC Joined under non-profit BAPM 2015 Quintiles Budgetary constraints 2015 Sanofi Lost main contact Can not attend meeting anymore and sound quality of policy 2015 SJA Healthcare Strategies meetings dial-in 2015 Society for Women’s Health Research (SWHR) Budgetary constraints 2015 University of Kansas Lost main contact No issues in particular. Just need to weigh how we expend our 2015 University of Maryland constantly shrinking resources.
Year Company Notes 2014 3G Biotech (China) Company Did not give a reason 2014 ab&c Did not give a reason 2014 Adriana Jenkins Foundation Suspended operations 2014 Biodesix Did not give a reason 2014 Boston Healthcare Did not give a reason 2014 Burrill & Company Suspended operations 2014 Companion Dx Reference Lab Did not give a reason 2014 CryerHealth Suspended operations 2014 El Camino Hospital Lost main contact 2014 Enterome Did not give a reason 2014 Genelex Corporation Budgetary constraints 2014 GenomeQuest, Inc. Did not give a reason 2014 Genomic Healthcare Strategies Did not give a reason 2014 Go Health America Lost main contact
12/14/16 Membership | p. 8 Organizations that have withdrawn from PMC 2007 thru December 8, 2016
Year Company Notes 2014 Growing Company Solutions, Inc. Suspended operations 2014 Health Advances, LLC Budgetary constraints this year. Will renew in 2015 2014 Ignyta Inc. Did not give a reason 2014 Institute for Personalized Medicine - Mary Kay Ross, M.D. Did not participate 2014 Intel Budgetary constraints Chose not to renew because the 10th Annual Personalized Medicine Conference is at the same time as the AMP conference, therefore 2014 Invivoscribe Technologies, Inc. they cannot attend it 2014 iSpecimen Inc. Did not participate 2014 Iverson Genetic Diagnostics, Inc. Being audited, unable to spend time and money on membership The staff does not feel they have the time and resources to maximize their partnership with PMC at this time. It is their hope to 2014 JPA (formerly Jones Public Affairs) revisit this in the next year or two.
With the change in the company's business model away from molecular diagnostics, Miraca decided not to renew its participation in the PMC. The company's staff members do appreciate the 2014 Miraca objectives and efforts of PMC, and wished us continued success. 2014 Nodality Did not give a reason 2014 Pamlab, LLC Lost main contact 2014 PanGenX Lost main contact 2014 Pathway Genomics Corporation Budgetary constraints 2014 Personalized Lifestyle Medicine Institute (PLMI) Did not give a reason 2014 PrimBio Research Institute LLC Too busy to attend meetings. 2014 PrimeraDX Acquired by Qiagen, another member 2014 RTI International Budgetary constraints 2014 Saladax Biomedical, Inc. Did not give a reason 2014 Sanford Rose Associates Budgetary constraints 2014 Scientia Advisors Bought by Precision for Medicine, another member 2014 SHINES Was only a member for 6 months. Did not participate. 2014 Tethys Bioscience Suspended operations The Dr. John T. Macdonald Foundation Department of Human 2014 Genetics, University of Miami Did not give a reason 2014 The Modellers, LLC Did not give a reason 2014 United States Diagnostic Standards, USDS Suspended operations 2014 University of Rochester Did not give a reason 2014 Wilson Sonsini Goodrich & Rosati Did not give a reason
Year Company Notes 2013 AdvaMed (Advanced Medical Technology Association) believes PMC is not neutral but biased towards clinical labs 2013 Affymetrix, Inc. budgetary constraints, but will potentially rejoin in 2014 2013 Allegro Diagnostics budgetary constraints, potentially interested in membership in 2014 2013 Almac Diagnostics did not participate/budget constrains, follow-up in fall for 2014 2013 Alper Biotech, LLC selling the company American Institute for Medical & Biological Engineering New management, reevaluting their memberships; May rejoin next 2013 (AIMBE) year 2013 American Liver Foundation main contact left 2013 American Society of Human Genetics (ASHG) Executive Committee is reevaluting all memberships 2013 Archon Genomics X PRIZE Prize closed 2013 Australian Institute for Bioengineering & Nanotechology did not give a reason 2013 BioMarker Strategies budgetary constraints main contact received new position and did not have time to 2013 Children's Hospital & Research Center Oakland participate 2013 Critical Path Institute (C-Path) did not give a reason limited ability to attend PMC meetings, problems addressed at the meetings are a bit off Cureline focus and nature of business. 2013 Cureline If goals realign, will definitely become members again.
12/14/16 Membership | p. 9 Organizations that have withdrawn from PMC 2007 thru December 8, 2016
Year Company Notes I think the future for personalized medicine is bright. Right now, though, it is not moving fast. We continue to review the waterfront, and for drugs outside of oncology, we have not found new candidates for pharmacogenomic testing—that is our sweet spot. Without much movement, I have put the monitoring of this area several levels down, and right now do not feel we would profit from the education and information available from PMC. So for now we will not renew, but hope we can jump back in once we get further 2013 CVS down the road with oncology. 2013 Cylex Inc. bankrupt 2013 Decatur Memorial Hospital did not give a reason 2013 DiagCor Biosciences Incorportion Limited did not give a reason 2013 Eurolab did not give a reason 2013 Fairbanks Institute for Healthy Communities reorganization of institute 2013 Fairleigh Dickinson University School of Pharmacy budgetary constraints, but will potential rejoin in 2014 Generation Health was bought by Medco/Express Scripts; Main contacted started new company, Metadiagnostics, but it never got 2013 Generation Health/Metadiagnostics off its feet. Found that the PMC is far too busy with topics that don’t affect the common/grassroots medical practitioner, would like to see more physician education. However because of PMC I am now involved in two personalized med/health start-ups, and for that I am very appreciative for the 2013 Genomix Canada numerous venues PMC has created. 2013 GENOPHEN Inc did not give a reason 2013 Hanson Wade did not give a reason 2013 IDBS budgetary constraints, but will potentially rejoin in 2014 2013 Instituto Cartuja Hospital Molecular did not give a reason 2013 Kilpatrick Townsend & Stockton LLP main contact left 2013 Medco Health Solutions, Inc. acquired by Express Scripts do not have bandwidth to participate as well as budget constraints, 2013 Merck but will potentially rejoin in 2014 2013 National Jewish Health did not give a reason 2013 NorthShore University HealthSystem budgetary constraints did not find that the program content was as relevant to their 2013 NuGEN business 2013 On-Q-ity went out of business PMC’s lobbying efforts are helpful and, in fact, we find ourselves immersed in bringing similar efforts forward on a local level across various fronts. However, we have decided to not continue with PMC this year as a function of prioritizing our overall lobbying 2013 Pappas Ventures expenses. 2013 Rare Genomics Institute budgetary constraints 2013 Selventa did not give a reason 2013 Siemens Medical Solutions budgetary constraints 2013 Silicon Valley Biosystems did not give a reason 2013 TcLand Expression went out of business still in start-up mood, conserving cash, management change. Follow- 2013 Telome Health, Inc. (THI) up in a few months 2013 The George Washington University Medical Center budgetary constraints, but will potentially rejoin in 2014 2013 University of South Florida College of Pharmacy lost main contact and did not participate 2013 Verinata Health Inc. acquired by illumnia 2013 VitaPath Genetics, Inc. ceased operations did not think membership was for individuals. Would like PMC to offer: 1) A section of PMC that would cater to the individual practitioner and the academic physician/researcher 2) For the PMC to begin to develop medical education, specifically, 2013 Your Genomic Doctor CME for the practitioner.
Year Company Notes 2012 AB&C Life Sciences, A division of Aloysius Butler & Clark 2012 AdvanDX 2012 ARCA biopharma
12/14/16 Membership | p. 10 Organizations that have withdrawn from PMC 2007 thru December 8, 2016
Year Company Notes 2012 ArcticDX Inc. 2012 Ascel Bio 2012 Asterand company is in debt, looking to be acquired 2012 Axial Biotech, Inc. 2012 BIOCRATES Life Sciences AG 2012 bioMérieux 2012 BioStat Solutions, Inc. 2012 Cardiovascular Research Center/ Mount Sinai School of Medicine 2012 Children's Mercy Hospitals & Clinics 2012 DNA Direct acquired by Express Scripts 2012 Gen-Probe Incorporated acquired by Hologic 2012 Growing Company Solutions, Inc. principal of company went to Qiagen 2012 Hoosier Oncology Group 2012 HP Health and Life Sciences 2012 Humana Inc. 2012 Informed Medical Decision Inc. 2012 Lead Horse Technologies, Inc. 2012 Malignant Hyperthermia Association of the US 2012 Medivo, Inc. 2012 MIT Center for Biomedical Innovation (CBI) 2012 NextBio 2012 Pacific Biosciences 2012 PAREXEL International 2012 Prognomix Inc. 2012 PRTM acquired by PwC 2012 ROBINSON, BRADSHAW & HINSON 2012 SAIC 2012 SomaLogic, Inc 2012 SureGene, LLC 2012 Translational Genomics Research Institute (TGen) 2012 Valerie August & Associates, LLC budget constrains 2012 William Blair
Year Company Notes 2011 Almac Diagnostics 2011 Association of Medical Diagnostics Manufacturers 2011 BD (Becton, Dickinson and Company) 2011 CancerGuide Diagnostics ceased operations 2011 Celera acquired by Quest 2011 Curidium Medica 2011 Dako Denmark A/S 2011 deCode Genetics 2011 Entelos 2011 Foley Hoag LLP 2011 Forest Laboratories formerly PGx Health 2011 Fox Chase Cancer Center 2011 Gentris Corporation 2011 Genzyme Corporation merged with Sanofi 2011 GHC Genetics Ltd 2011 HistoRx purchased by Genoptix, a Novartis company 2011 IBM Healthcare and Life Sciences 2011 IDA Ireland 2011 Institute of Genomic Medicine, UMDNJ-New Jersey 2011 Interleuken Genetics, Inc. 2011 Invivoscribe Technologies, Inc. 2011 JMP Securities 2011 Laboratory for Personalized Molecular Medicine 2011 Lemhi Ventures 2011 Lineagen, Inc. 2011 Navigenics, Inc. 2011 Premier Source 2011 Proventys ceased operations, CDS Oncology assets acquired by McKesson 2011 RedPath Integrated Pathology, Inc.
12/14/16 Membership | p. 11 Organizations that have withdrawn from PMC 2007 thru December 8, 2016
Year Company Notes 2011 Rosetta Genomics 2011 Scripps Research Institute 2011 Shady Grove Adventist Hospital 2011 The Institute for Individualized Health (IGNITE) 2011 Transgenomics, Inc. 2011 Ventana Medical Systems, a Roche Company
Year Company Notes 2010 (AACC) American Association of Clinical Chemistry 2010 Allegro Diagnostics 2010 Arrowhead Publishers and Conferences 2010 Baylor College of Medicine 2010 Biosearch Technologies, Inc. 2010 Deloitte Center for Health Solutions 2010 Diaceutics 2010 Diagnostic Advisors 2010 DNA Vision s.a. 2010 DxS Limited acquired by Qiagen 2010 Expression Pathology 2010 GeneDx 2010 Genomas Inc. 2010 Genoptix Medical Laboratory acquired by Novartis 2010 Georgetown University School of Nursing & Health Studies 2010 Helicos Bioscience 2010 Hyperthrophic Cardiomyophathy Association-HCM 2010 Institute for Individualized Medicine 2010 Kimball Genetics, Inc. acquired by LabCorp 2010 Merrimack Pharmaceuticals 2010 Molecular Imaging 2010 Monogram Biosciences acquired by LabCorp 2010 Nanosphere, Inc. 2010 National Coalition for Health Professional Education in Genetics 2010 OncoMethylome Sciences 2010 ParagonDx ceased operations 2010 SciTech Strategies, Inc. 2010 Sequenom Center for Molecular Medicine 2010 The Personalized Medicine Group of Connecticut
Year Company Notes 2009 5AM Ventures 2009 AstraZeneca 2009 Aureon Laboratories, Inc. 2009 Aviir 2009 BG Medicine 2009 Burrill & Company 2009 Center for Molecular Medicine 2009 ChemGenex Pharmaceuticals, Inc. acquired by TEVA 2009 Cincinnati Children's Hospital Medical Center 2009 Clear Point Health 2009 Curidium merged with Avacta 2009 Gene Express Inc. 2009 Gene Logic 2009 Gene Network Science (GNS), Inc. 2009 GenVault, Corp. acquired by IntegenX 2009 Hadassah 2009 HistoRx 2009 Hudson-Alpha Institute for Biotechnology 2009 Institute for Genomics & Systems Biology 2009 Lipomics acquired by Tethys Bioscience 2009 Manatt Health Solutions 2009 Mintz Levin 2009 Navigenics, Inc. 2009 Osmetech Molecular Diagnostics 2009 PENN Medical
12/14/16 Membership | p. 12 Organizations that have withdrawn from PMC 2007 thru December 8, 2016
Year Company Notes 2009 Perlegen ceased operations 2009 PrimeraDx 2009 Progenika 2009 The DNA Repair Company merged with CELLective Diagnostics to form On-Q-ity 2009 TheraGenetics, Ltd. acquired by Avacta Group plc 2009 Ventana Medical Systems, a Roche Company
Year Company Notes 2008 Bio Research Support, Inc. 2008 Boston Millennia Partners 2008 CELLective Diagnostics merged with The DNA Repair Company to form On-Q-ity 2008 Center for Medicine in the Public Interest 2008 DNAPrint genomics, inc. ceased operations 2008 Exagen Diagnostic 2008 Genetics, Ethics & Policy Consulting 2008 IDA Ireland 2008 Karolinska Institutet 2008 Mirixa 2008 Nanogen acquired by The ELITech Group 2008 NeuroMark 2008 Pri-Med Institute 2008 SaffronTechnologies, Inc. 2008 Stephens Investment Management 2008 The RPM Report 2008 WellPoint 2008 Xanthus Pharmaceuticals acquired by Antisoma
Year Company Notes 2007 Pathway Diagnostics 2007 PharmaSouth 2007 Rand 2007 Sarcoma Foundation 2007 Theranos, Inc 2007 TM Bioscience merged with Luminex
12/14/16 Membership | p. 13
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Membership | p. 14 Membership | p. 15
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Membership | p. 16 2016 New Members
Company Name Category 1 Altan Pharma Ltd. Emerging Biotech/Pharmaceutical Companies 2 Ariel Precision Medicine Clinical Laboratory Testing Services 3 AveXis Emerging Biotech/Pharmaceutical Companies 4 Biocom Industry/Trade Association 5 Biological Dynamics, Inc. Diagnostic Companies Brigham and Women’s Hospital, Genomes2People 6 Research Program Research, Education & Clinical Care Institutions 7 Centro de Genomas Clinical Laboratory Testing Services 8 CKSA Strategic Partners 9 Clarity LLC Strategic Partners 10 Empire Genomics, LLC Clinical Laboratory Testing Services 11 FaegreBD Strategic Partners
12 Flatiron Health IT/Informatics Companies 13 GlobalData PLC Strategic Partners 14 GNS Healthcare IT/Informatics Companies 15 Harvard Business School Research, Education & Clinical Care Institutions 16 Harvard Pilgrim Health Care Health Insurance Companies 17 Health Advances, LLC Strategic Partners 18 Health Decisions Personalized Medicine Service Providers Hospital Universitari Vall d'Hebron - Institut de Research, Education & Clinical Care Institutions 19 Recerca (VHIR) 20 Inivata Diagnostic Companies 21 Invivoscribe Diagnostic Companies 22 Massive Bio, Inc. Personalized Medicine Service Providers 23 Merck Large Biotech/Pharmaceutical Companies 24 Navigant Strategic Partners 25 Precision Health Initiative at Cedars-Sinai Research, Education & Clinical Care Institutions Raabe College of Pharmacy, Ohio Northern 26 University Research, Education & Clinical Care Institutions 27 Seven Bridges IT/Informatics Companies 28 Tabula Rasa HealthCare, Inc. Personalized Medicine Service Providers 29 Teal Lion LLC Strategic Partners 30 University of Rochester Research, Education & Clinical Care Institutions 31 Unum Therapeutics Emerging Biotech/Pharmaceutical Companies 32 Wake Forest Baptist Medical Center Research, Education & Clinical Care Institutions 33 Washington Media Group Strategic Partners 34 West Cancer Center Research, Education & Clinical Care Institutions
2017 New Members 1 Bruce Quinn Associates Strategic Partners 2 Celcuity, LLC Diagnostic Companies 3 Guardant Health Diagnostic Companies 4 Ignyta Emerging Biotech/Pharma Company 5 OmniSeq Diagnostic Companies Sylvester Comprehensive Cancer Center 6 University of Miami Research, Education & Clinical Care Institutions 7 The North Carolina Biotechnology Center Research, Education & Clinical Care Institutions
Membership | p. 17
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Membership | p. 18 Current Target List for 2017 Membership
AbbVie Indivumed Accenture Invitae Agilent/Dako Keck Graduate School Agios MD Labs Alliance for Cancer Gene Therapy Medivo Ambry Genetics Memorial Sloan Kettering Cancer Center Arizona State University Metastat Bayer Myriad Genetic Laboratories, Inc. Bethesda Group Neon Therapeutics Biocartis Northeastern University Biogen Northrup Grumman Biomarker Strategies Nutrigenomix BioStat Solutions, Inc. OptumLabs Blue Cross Blue Shield Association ORIEN Booz Allen Ovarian Cancer National Alliance Broad Institute Pancreatic Cancer Action Network Cancer Genetics PathGroup Cancer Support Community PPD Cardinal Health Precision Ready CardioDx Premaitha CareCore National Priority Health Celgene Research Inst of McGill Univ Health Centre Cerner Robert H. Lurie Comprehensive Cancer Ctr Claritas Genomics Northwestern University Community Oncology Alliance Sanofi Complete Genomics, Inc. Society for Women’s Health Research Conatus Consulting Spectrum Pharmaceuticals CVS/Caremark Standard Molecular Cystic Fibrosis Foundation Swedish Cancer Institute Daiichi Sankyo Takeda Dana-Farber Cancer Institute The Charles Bronfman Institute for Dell Healthcare & Life Sciences Personalized Medicine Denovo Biomarkers UCSF Dignity Health University of Chicago Medicine Empiriko University of New Mexico Galderma UNC Eshelman School of Pharmacy Geisinger Health System Veracyte Genoprimer Vertex Gibbs Health Institute Walgreens Gilead Waters Corporation Gordon Thomas Honeywell Gov. Affairs WAVE Life Sciences Gristone Oncology Wildtype Advisors GV (Google Ventures) HalioDx Healthios Health Care Service Corporation Health Transformation Alliance Humana Human Longevity IBM Watson IES Diagnostics
Membership | p. 19
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Membership | p. 20 Membership | December 2016
CLINICAL LABORATORY INDUSTRY/TRADE National Patient Advocate Knight Cancer Institute - STRATEGIC PARTNERS TESTING SERVICES ASSOCIATIONS Foundation Oregon Health & Sciences Arnold & Porter LLP AlphaGenomix Laboratories American Clinical Laboratory One Disease at a Time University Avalere Health ARIEL Precision Medicine Association Manchester University Bioscience Valuation BSV Centro de Genomas BIO (Biotechnology PERSONALIZED School of Pharmacy GmbH Clinical Reference Innovation Organization) MEDICINE SERVICE Marshfield Clinic Cambridge Healthtech Laboratory, Inc. Biocom PROVIDERS Mayo Clinic Institute Empire Genomics PhRMA 23andMe MD Anderson – Institute for CKSA Laboratory Corporation of Cure Forward Personalized Cancer Clarity Research & America (LabCorp) IT/INFORMATICS Health Decisions Therapy Consulting Metabolon, Inc. COMPANIES InformedDNA Mission Health, Fullerton Co-Bio Consulting, LLC Proove Biosciences 5AM Solutions, Inc. Intervention Insights Genetics Center ConText Quest Diagnostics Change Healthcare KEW Group Moffitt Cancer Center ConvergeHEALTH by Cytolon AG Massive Bio National Foundation for Deloitte DIAGNOSTIC COMPANIES DNAnexus Michael J. Bauer, M.D. & Cancer Research Credit Suisse Abbott Flatiron Health Associates, Inc. National Pharmaceutical Defined Health Adaptive Biotechnologies Genospace MolecularHealth Council EdgeTech Law LLP Agendia NV GNS Healthcare MolecularMatch North Carolina Ernst & Young Global Life Alacris Theranostics GmbH Inspire NantHealth Biotechnology Center Sciences Center Almac Diagnostics Intel Corporation N-of-One, Inc. NorthShore University Feinstein Kean Healthcare AltheaDX M2Gen Perthera HealthSystem FaegreBD Consulting Assurex Health, Inc. McKesson Precision for Value Ontario Genomics Institute Foley Hoag LLP ASURAGEN, Inc. NextGxDx Tabula Rasa HealthCare, Inc. Partners HealthCare Foley & Lardner LLP BD (Becton Dickinson & Oracle Health Sciences Personalized Medicine Genome magazine Company) Seven Bridges RESEARCH, EDUCATION Poliambulatorio Euganea GlobalData PLC Biological Dynamics, Inc. Syapse & CLINICAL CARE Medica Goldbug Strategies, LLC Brain Resource Company UNIConnect, LC INSTITUTIONS Precision Health Initiative at HealthFutures, LLC Limited XIFIN, Inc. American Association for Cedars-Sinai Health Advances, LLC Caprion Proteomics Cancer Research (AACR) Qatar Biobank Hogan Lovells LLP CareDx, Inc. LARGE BIOTECH/ American Medical The Quebec Network for Jared Schwartz MD, PhD, Caris Life Sciences PHARMACEUTICAL Association (AMA) Personalized Health Care LLC Celcuity, LLC COMPANIES Association for Molecular Raabe College of Pharmacy, The Journal of Precision Counsyl Amgen, Inc. Pathology (AMP) Ohio Northern University Medicine Exosome Diagnostics Astellas Pharma Global Baylor Health Care System Roswell Park Cancer Kinapse Foundation Medicine, Inc. Development Precision Medicine Institute L.E.K. Consulting GeneCentric Diagnostics AstraZeneca Institute Rutgers Cancer Institute of McDermott Will & Emery Genomic Health, Inc. Pharmaceuticals Brigham and Women’s New Jersey Navigant Guardant Health Boehringer-Ingelheim Hospital, Genomes2People Sanford Imagenetics, Nixon Peabody LLP Human Longevity Pharmaceuticals, Inc. Research Program Sanford Health Pendergast Consulting Indi – Integrated Diagnostics Bristol-Myers Squibb Brown University Stanford University School of Personalized Medicine in Inivata Eli Lilly and Company Cancer Treatment Centers Medicine OncologyTM Interleukin Genetics, Inc. EMD Serono of America Sutter Health Personalized Medicine Invivoscribe Technologies, Endo Health Solutions Catholic Health Initiative’s Sylvester Comprehensive World Conference Inc. Genentech, Inc. Center for Translational Cancer Center – PricewaterhouseCoopers Luminex Corporation GlaxoSmithKline, PLC Research University of Miami LLP Metamark Genetics, Inc. Johnson & Johnson The Christ Hospital UC Davis Mouse Biology Professional Genetic MolecularMD Merck & Co. College of American Program Interactions NanoString Technologies Teva Pathologists University of Alabama, Quorum Consulting OmniSeq Novartis Coriell Institute for Medical Birmingham Slone Partners Personal Genome Pfizer, Inc. Research University of Florida Spectrum Diagnostics (PGDx) CREATE Health University of Pennsylvania Teal Lion, LLC QIAGEN, Inc. PATIENT ADVOCACY Translational Cancer Health System Vital Transformation RIKEN GENESIS GROUPS Centre, Lund University University of Pittsburgh Washington Media Group Roche Diagnostics Accelerated Cure Project for Duke Center for Research Medical Center (UPMC) Corporation Multiple Sclerosis on Personalized Health University of Rochester VENTURE CAPITAL Siemens Healthcare Alliance for Aging Research Care University of South Florida GreyBird Ventures, LLC Diagnostics, Inc. Bonnie J. Addario Lung Essentia Institute of Rural Morsani College of Kleiner Perkins Caufield & SomaLogic, Inc. Cancer Foundation Health Medicine Byers SurExam Bulgarian Association for Genome British Columbia The University of Texas Mohr Davidow Ventures Personalized Medicine Genome Canada System Third Rock Ventures, LLC EMERGING BIOTECH/ Friends of Cancer Research Génome Québec Vanderbilt University Medical PHARMACEUTICAL Global Liver Institute Harvard Business School Center COMPANIES HealthyWomen Helmholtz Zentrum München Virginia Commonwealth Altan Pharma, Ltd. International Cancer Hospital Universitari Vall University Health System AveXis Advocacy Network d'Hebron Wake Forest Baptist Medical Ignyta ("ICAN") Indiana Institute of Center Syros Pharmaceuticals LUNGevity Foundation Personalized Medicine West Cancer Center Unum Therapeutics Melanoma Research Inova Health System RESEARCH TOOL Zinfandel Pharmaceuticals, Alliance Foundation Instituto de Salud Carlos III COMPANIES Inc. Multiple Myeloma Research Intermountain Healthcare Cynvenio Biosystems, Inc. Foundation International Society of DNA Genotek, Inc. HEALTH INSURANCE National Alliance for Personalized Medicine Genia Technologies COMPANIES Hispanic Health The Jackson Laboratory Illumina, Inc. Harvard Pilgrim Health Care Thermo Fisher Scientific
Membership | p. 21
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Membership | p. 22 Membership | p. 23
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Membership | p. 24 2016 Sponsorship State of Personalized Medicine Luncheon American Clinical Laboratory Alan Mertz Association $ 1,000 Marcia Kean Feinstein Kean Healthcare $ 1,000 Dan Leonard National Pharmecutical Council $ 1,000 Andrea Masciale Johnson & Johnson $ 30,000 $ 33,000 Unrestrticted Lori M. Reilly, Esq. PhRMA $ 50,000 Lori M. Reilly, Esq. PhRMA $ 75,000 $ 125,000 Clinical and Economic Value of Next-Generation Sequencing Marcia Eisenberg Labcorp $ 10,000 Chris Cournoyer N-of-One $ 10,000 Scott Boyle Caris Life Sciences $ 20,000 John Leite Illumina $ 20,000 Mike Pellini Foundation Medicine $ 25,000 Hakan Sakul Pfizer $ 25,000 Lena Chaihorsky QIAGEN, Inc. $ 25,000 Rob Dumanois Thermo $ 25,000 $ 160,000 12th Annual Personalized Medicine Conference at Harvard Medical School Bill Dalton M2Gen $ 1,000 Kent Lloyd UC Davis Mouse Biology Program $ 1,000 Michael Stocum Inivata $ 3,150 Christa Kerkorian Agios $ 5,000 Grants Office AstraZeneca $ 5,000 Tom McEnery Change Healthcare (formerly Emdeon)$ 5,000 Marcia Kean Feinstein Kean Healthcare $ 5,000 *plus $10,000 in kind Kim Popovits Genomic Health $ 5,000 Tom Miller GreyBird $ 5,000 Jeff Leerink Leerink Partners $ 5,000 National Foundation for Cancer Sujuan Ba Research $ 5,000 Dan Leonard National Pharmecutical Council $ 5,000 David Resnick Nixon Peabody $ 5,000 Mark Levin Third Rock Ventures, LLC $ 5,000 J. Brian Munroe Endo Health Solutions $ 10,000 Rouget Henschel/ Mayumi Willie Foley & Lardner LLP $ 10,000 Sarah Cueto Invivoscribe $ 10,000 Scott Sutton L.E.K. $ 10,000 Les Paul Molecular Health $ 10,000 Brad Gray NanoString Technologies $ 10,000 Tara Kochis-Stach Slone Partners $ 10,000 Rachel Radomski Vertex $ 10,000 George Telepan Bristol-Myers Squibb Company $ 15,000 Damon Hostin Catholic Health Initiative Dignity Health - $Precision 15,000 Medicine Alliance Amy Abernethy Flatiron Health $ 15,000 Mike Pellini Foundation Medicine, Inc. $ 15,000 Jonathan Sheldon/Clare Gaul Oracle Health Sciences $ 15,000 Hakan Sakul Pfizer Inc. $ 15,000 Anne Magnus Seven Bridges $ 15,000 Vanessa Gannon Genentech $ 17,500 Kate Claessens Roche Diagnostics Corporation $ 17,500 Stephen L. Eck/Mary Lacey Astellas Pharma US, Inc. $ 25,000 Tazia Taylor Intermountain Healthcare $ 35,000 $ 340,150 PM Adoption Case Study Report- PMC and FKH Project 2016 Chris Cournoyer N-of-One $ 5,000 $ 5,000 Total $ 663,150
Membership | p. 25
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7. Public Policy
August 10, 2016 BOARD OF DIRECTORS President Mr. Glenn McGuirk Edward Abrahams, Ph.D. Division of Ambulatory Services Chair William S. Dalton, Ph.D., M.D. Hospital and Ambulatory Policy Group M2Gen Centers for Medicare & Medicaid Services Vice Chair 7500 Security Boulevard Stephen L. Eck, M.D., Ph.D. Astellas Pharma Global Development Baltimore, MD 21244-1850 Treasurer D. Stafford O’Kelly Re: 2016 Preliminary Gapfill Payment Determinations for New GSP and Altan Pharma, Ltd. MAAA CPT Codes Secretary Amy P. Abernethy, M.D., Ph.D. Flatiron Health Dear Mr. McGuirk: Past President & Chair J. Brian Munroe Endo Pharmaceuticals On behalf of the Personalized Medicine Coalition (PMC), I am pleased to submit comments Steven D. Averbuch, M.D. on the Centers for Medicare & Medicaid Services (CMS)’ 2016 Preliminary Gapfill Payment Bristol-Myers Squibb Company Determinations for Multianalyte Assays with Algorithmic Analyses (MAAA) and Genomic Paul R. Billings, M.D., Ph.D. Sequencing Procedures (GSP). Biological Dynamics, Inc. Neil de Crescenzo Change Healthcare The Preliminary National Limitation Amounts (Preliminary NLAs), if finalized, would Donna Cryer, J.D. represent drastic reductions in payment rates, by 30 – 90 percent, for tests deemed reasonable Global Liver Institute and necessary. To assure continued access to them, we request that the NLAs be adjusted to Tim Garnett, FRCOG, MFFP, FFPM prevent such drastic reductions in the 2016 Final Gapfill Payment Determinations. Such Eli Lilly and Company adjustment will also help to avoid substantial changes in payment during the implementation Julie K. Goonewardene of the Protecting Access to Medicare Act of 2014 (PAMA). As you know, Section 216 of The University of Texas System PAMA is a re-pricing exercise that is just at the start of implementation. Getting this process Howard McLeod, Pharm.D. Moffitt Cancer Center right is critical to the future of personalized medicine. Michael Pellini, M.D. Foundation Medicine Personalized medicine is an evolving field in which physicians use diagnostic tests to Kimberly J. Popovits determine which medical treatments will work best for each patient. By combining the data Genomic Health from those tests with an individual’s medical history, circumstances and values, health care Lori M. Reilly, Esq. providers can develop targeted treatment and prevention plans. Personalized medicine PhRMA therefore has the potential to optimize delivery and dosing of treatments so patients can Hakan Sakul, Ph.D. Pfizer Inc. receive the most benefit with the least amount of risk, eliminating the difficulties of the trial- Jared N. Schwartz, M.D., Ph.D. and-error process many patients endure to obtain the correct diagnosis and treatment for their Jared N. Schwartz, M.D., Ph.D., LLC condition. Michael Vasconcelles, M.D. Unum Therapeutics PMC is an educational and advocacy nonprofit organization that promotes the understanding Jay G. Wohlgemuth, M.D. Quest Diagnostics and adoption of personalized medicine to benefit patients and the health care system. We represent more than 240 institutions, including academic, patient, provider, and payer organizations as well as drug and diagnostic manufacturers and clinical laboratories. Given the missions and desires of the patient and health care stakeholder communities we bring together, PMC has a keen interest in CMS’ 2016 Clinical Laboratory Fee Schedule (CLFS) Gapfill Payment Amounts.
Overall, PMC members are concerned that insufficient payment amounts threaten the sustainability of the laboratory industry and continued investment in the developing field of
Public Policy | p. 1 personalized medicine, thereby removing the promise of sustaining innovation in health care and possibly lowering overall costs by eliminating unnecessary and/or ineffective treatments.
Specifically, this proposed gapfill payment schedule:
• Confuses stakeholders due to the lack of transparency in the gapfill process • Reduces the quality of patient care and patient access • Threatens the future of health care by not addressing potential unintended consequences
I. PMC is concerned about the level of stakeholder engagement and the lack of transparency in the gapfill process.
PMC is concerned with how the gapfill process unfolded in this case. To determine gapfill amounts, Medicare Administrative Contractors (MACs) should use the four criteria consistent with 42 C.F.R. 414.508(b)(1). Particularly, payments should cover the resources required to develop and perform these tests, including reasonable costs for supplies, equipment, clinical labor, test performance, operating a clinical laboratory, research and development, and the continuous process improvements required for testing and, often, test interpretation. In addition, consistent with Section 216 of PAMA and current gapfill criteria, significant weight should be given to rates established by other payers for these tests, since some MACs have more experience with the tests than others. For example, current Medicare payment rates for those MAAA gapfill tests that have had long-established payment rates under unlisted codes in the past were established through an open process with local MACs that cover the tests that addressed the gapfill criteria. Those rates should be upheld.
To bring transparency to this process, CMS should require all MACs to disclose pricing methodology and describe the data used to determine their new payment schedule. Furthermore, we ask that this process be revisited and revised to be as transparent as possible. One suggestion is that CMS require MACs to engage with stakeholders in their jurisdiction, so that MACs can make educated decisions on the tests offered to define accurate and reasonable prices. We ask for significant stakeholder engagement, including public meetings, at each step of a new process resulting in payments that are evidence-based, transparent, and reflect the costs associated with these tests.
PMC understands that other stakeholders are developing models to better evaluate the resources required to perform these tests and more accurately reflect the relative amounts of work involved as the volume of genomic sequences analyzed increases. We encourage CMS to consider these proposals, and to ensure that the final gapfill pricing for tests provides an adequate basis for their continued offering to Medicare and Medicaid beneficiaries.
II. PMC is concerned about the impact that inadequate payments will have on patient access to high-quality care.
PMC is concerned that inadequate payments are, in essence, a non-coverage decision with the potential to negatively impact treatment decision-making by patients and their health care providers. Coverage decisions should be determined through a separate process. De facto non-coverage through payment decisions is not appropriate.
Limiting access to personalized medicine will delay getting the right treatment to the right patient. It will lock in our current one-size-fits-all, trial-and-error system that all stakeholders, including payers but most importantly patients, would like to move beyond. Identifying the right treatment for the right patient the first time will enable the delivery of high-quality, more efficient, higher value care, which is better for patients and better for the health system.
We must also acknowledge PAMA implementation here. CMS has worked with stakeholders on the proposed rule and adjusted it before publishing the final rule. Implementation has begun. Drastically altering current payment rates for covered tests negatively impacts that process and thus is in violation of the spirit of the law.
2 Public Policy | p. 2
III. PMC is concerned about the unintended consequences of the proposed gapfill payments on the future of personalized medicine.
Personalized medicine is changing how medicine is practiced. Its impact is notably evident in serious and life threatening conditions that have previously lacked efficacious treatments. Through the use of innovative diagnostics, health care quality is increasing while the health care system becomes more efficient. However, poorly developed and executed policy decisions, like the gapfill payment process, will negatively impact health care quality improvements by discouraging the development of new tools in the life sciences.
We are also concerned about the consequences for patient access to the tests they require. While large laboratories have diverse menus of services, PMC’s membership includes labs that focus exclusively on personalized medicine diagnostics. With payments set at markedly lower levels, we fear these labs will go out of business and if their technology is not acquired, the test will no longer be offered; a danger that is particularly important for those with rare conditions. This disruption will endanger patients’ and their health care providers’ access to testing, ultimately hindering the benefits of personalized medicine in health care.
We ask that CMS consider these unintended consequences of gapfill payment decisions and other policies as they work through this issue.
Conclusion
Coverage and payment decisions should be separate processes. When CMS decides to cover a test, we ask that the payment reflect the reasonable cost of performing that test in a high-complexity laboratory by highly trained professionals, as well as covering the associated research and development costs and capital returns required to attract innovators to the industry. Without this support, the future ability of personalized diagnostics to improve patient care may be compromised and, quite simply, new tests will not be developed and important currently offered tests may be discontinued. Thus, patient access to new and improved treatments will suffer.
PMC appreciates the opportunity to provide comments on the 2016 Gapfill Payment Amounts. If you have any questions about these comments, please contact me at 202-589-1770 or via e-mail at [email protected].
Sincerely yours,
Amy M. Miller, Ph.D. Executive Vice President
3 Public Policy | p. 3
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Public Policy | p. 4
2016 BIO INTERNATIONAL CONVENTION
Personalized Medicine & Diagnostics Track
TUESDAY, JUNE 7, 2016
3:30 - 4:30 p.m. — 30 Years of Genomics — Bridging the Past with the Future Room West 3003
The Human Genome Project was first publicly discussed 30 years ago when Renato Dulbecco published an essay in a March issue of Science and workshops were held in Santa Fe and Cold Spring Harbor. Since then genome sequencing has permeated academic labs and is quickly becoming affordable for the average healthcare provider – but what is next? The panel will briefly reflect on how the Human Genome Project has changed biology, ushering in a new era of partnership and data sharing, and then delve into the pressing questions of how to fully realize the promise, including achieving the goals of President Obama’s Precision Medicine Initiative. How will we handle the challenges of big biology, including the tsunami of genetic data which will soon outstrip that generated by astronomy, YouTube and Twitter? Also, what did the Human Genome Project miss in the “dark matter” of the genome that is not easily penetrated by conventional sequencing methods? Lastly, panelists will discuss the pending widespread availability of genomic information and what affect this may have in the decades to come.
Introduction
Edward Abrahams, Ph.D., President, Personalized Medicine Coalition
Speakers
David Barker, formerly Chief Scientific Officer, Illumina
Jim Blair, Partner, Domain Associates (moderator)
Erik Holmlin, President & CEO, BioNano Genomics
Pieter van Rooyen, CEO, Edico Genome
6:30 - 9:30 p.m. — BIO, Burgundy and Business —Foley & Lardner / PMC Cocktail Reception
RN74 301 Mission Street San Francisco, CA 94105
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WEDNESDAY, JUNE 8, 2016
10:45 a.m. - 12:00 p.m. — Lifespan or Healthspan: Is it Time for a Paradigm Shift? An Interview with William N. Hait, Global Head, R & D, Janssen Pharmaceutical Companies of Johnson & Johnson Room West 3005
Research!America is bringing together two thought leaders, Dr. Bill Hait, Global Head of Janssen Research & Development, LLC, and Dr. Keith Yamamoto, Vice Chancellor of Research and Executive Vice Dean at the University of California, San Francisco to discuss “immorbidity,” a perspective on medicine in which the priority shifts from treating or curing diseases like cancer and Alzheimer’s to preventing and delaying them. Dr. Hait and Dr. Yamamoto will discuss the science and policy rationale behind this concept, its roots in personalized medicine, its particular relevance to oncology, and the case for a major shift in investment and effort within the life sciences enterprise away from post-symptom to pre-symptom care.
Introduction
Edward Abrahams, Ph.D., President, Personalized Medicine Coalition
Speakers
Mary Woolley, President, Research!America
William Hait, Global Head, R & D, Janssen Pharmaceutical Companies of Johnson & Johnson
Keith Yamamoto, Vice Chancellor for Research, University of California, San Francisco (moderator)
1:00 – 2:00 p.m. — Building Personalized Medicine Policy: The 21st Century Cures and Healthier Americans Legislative Proposals
Room West 3005
The science driving personalized medicine continues to push innovation toward better patient care. Successful integration of personalized medicine into the healthcare system requires scientific discovery and technology development incentives as well as appropriate policies governing regulatory oversight and access to care. The U.S. House of Representatives recently introduced the 21st Century Cures legislation, which is meant to help streamline the pathway for novel medical technologies to become available to patients and address many of the issues facing personalized medicine. Early in 2016, the U.S. Senate introduced a series of smaller companion bills as part of their Healthier Americans Legislation. This panel will provide insight into the development of these legislative proposals, provide an update on their current status and chances of passage in an election year and explore the potential impact that these bills will have on medical research, product development, regulatory oversight, coverage and reimbursement in healthcare delivery.
Speakers
Amy M. Miller, Executive Vice President, Personalized Medicine Coalition (moderator)
Public Policy | p. 6
Wade Ackerman, formerly Senior FDA Counsel, U.S. Senate Health, Education, Labor & Pensions Committee
Clay Alspach, formerly Counsel, U.S. House of Representatives Energy and Commerce Committee
Sara Radcliffe, President & CEO, California Life Sciences Association
2:15 – 3:15 p.m. — Personalized Health as a Potential Enabler of Personalized Medicine Room West 3005
We have now reached a point, scientifically, where we can begin to understand one’s predisposition to disease and work throughout their lifetime to predict and prevent disease resulting in an increased productive lifespan. Our healthcare system is fraught with regulation red tape, reimbursement uncertainty and financial stress. The American healthcare system is reactionary rather than preventative and it incentivizes treatment of the ill rather than health maintenance. To fully realize the promise of personalized medicine, patients and healthy individuals must be engaged in their own health and in their own healthcare decisions. Thus, a focus must be placed on "personalized health” with the ultimate goal to understand the underlying molecular mechanisms which translate one’s genomic characteristics and environmental exposures into individual predisposition to disease. This session will discuss how a convergence of these fields can transform the healthcare system into one that is both preventative and proactive to ultimately reach a lower systemic cost.
Speakers
David Benaron, Chief Medical Officer, JAWBONE
Linda Molnar, CEO, Simpatica Medicine, Inc. (moderator)
Walter Stewart, Vice President, Chief Research Officer, Sutter Health
Ben Wiegand, Global Head of the Disease Interception Accelerator (DIA), Johnson & Johnson
3:30 – 4:30 p.m. — Strategic Investment in Precision Medicine: Where to Put Your ‘Omics Dollars, NOW Room West 3005
As global precision medicine interest takes hold and the industry has a stronger experience base of value creation and value destruction, investors are rethinking their growth strategies. M&A and strategic partnerships that allow organizations to access the most innovative offerings and de-risk their total investment are issues that are top of mind. With the underlying technologies and the applications of diagnostics becoming more complex, so do investment and partnering decisions. EY Life Sciences transaction leaders and key stakeholders will assemble this panel as they explore the central issues in choosing the right acquisition target or strategic partner, structuring a mutually beneficial partnership and deciding how to continue to invest based on risk tolerance and desired level of control.
Public Policy | p. 7
Speakers
William Clifford, Partner, Oberland Capital
Luba Greenwood, Vice President, Mergers & Acquisitions and Business Development, Roche
Justin Kao, Senior Vice President of Corporate Development, Operations and Strategy, Helix
James McCullough, Managing Partner, Renwick Capital
Kristin Pothier, Global Head of Life Sciences, Parthenon-EY (moderator)
Alex de Winter, Director, GE Ventures
4:30 – 5:30 p.m. — Digital Health & Personalized Medicine Track Reception Room West Third Floor Lobby
THURSDAY, JUNE 9, 2016
9:00 - 10:15 a.m. — “What Goes Around Comes Around:” Applying Lessons Learned from Personalized Medicine on Evidence and Payer Coverage Requirements to Digital Health Room West 3005
Digital health is an emerging and amorphous field that encompasses everything from electronic health records to fitness apps making it difficult to grasp the real value of some of these technologies. This is not a new challenge, as personalized medicine has been grappling with similar issues since the dawn of the genomics era. This highly interactive panel will draw on the perspectives of academic researchers, venture capitalists and industry leaders to discuss “lessons learned” about evidence and payer coverage requirements from personalized medicine and how they apply to digital health.
Speakers
Rowan Chapman, Managing Director, New Business Ventures, GE Ventures
Deborah Kilpatrick, CEO, Evidation Health
Nicole Littmann, Vice President, Client Services, Quorum Consulting
Kathryn Phillips, Professor, USCF (moderator)
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10:30 – 11:30 a.m. — Companion Diagnostics: The Evolving Need for Progressive Partnerships Between Pharma and Diagnostics Companies Room West 3005
The business case for companion diagnostics is in jeopardy. Cost pressures on payers are pushing new stakeholders to bear risk. Groundbreaking deals between various stakeholders to form deeper partnerships that provide for the sharing of both risk and upside are beginning to form. This session will feature a diverse panel of representatives from various stakeholder perspectives to further explore what is driving these new partnerships, what the value proposition is from each perspective and what the expectations are moving forward.
Speakers
Steven Arrivo, Senior Director of Business Development, Biodesix: Making Medicine Personal
Gary Gustavsen, Vice President, Health Advances (moderator)
Matthew Hawryluk, Executive Vice President and Chief Business Officer, Gritstone Oncology
Werner Verbeist, Global Head, Janssen Diagnostics
Public Policy | p. 9
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June 28, 2016 BOARD OF DIRECTORS President Edward Abrahams, Ph.D. Chair Institute for Clinical and Economic Review William S. Dalton, Ph.D., M.D. Two Liberty Square, Ninth Floor M2Gen Boston, MA 02109 Vice Chair Stephen L. Eck, M.D., Ph.D. Astellas Pharma Global Development By electronic delivery Treasurer D. Stafford O’Kelly Re: Non-small Cell Lung Cancer Scoping Document Altan Pharma, Ltd. Secretary Amy P. Abernethy, M.D., Ph.D. Dear Dr. Pearson: Flatiron Health Past President & Chair J. Brian Munroe I am writing on behalf of the Personalized Medicine Coalition (PMC) in response to the Endo Pharmaceuticals recently published scoping document titled “Treatment Options for Advanced Non-Small- Steven D. Averbuch, M.D. Cell Lung Cancer: Effectiveness, Value, and Value-Based Price Benchmarks.” Bristol-Myers Squibb Company Paul R. Billings, M.D., Ph.D. PMC is comprised of more than 240 member institutions representing a wide range of Biological Dynamics, Inc. stakeholders, including patient groups, provider groups, payers, health care delivery Neil de Crescenzo Change Healthcare organizations, diagnostic and pharmaceutical manufacturers, and clinical laboratories. Our Donna Cryer, J.D. members work to address issues in science, business and policy that impact personalized Global Liver Institute medicine. Tim Garnett, FRCOG, MFFP, FFPM Eli Lilly and Company We sincerely appreciate Rick Chapman taking time to address PMC’s public policy Julie K. Goonewardene committee on June 21, 2016, and hope that this meeting was the beginning of a constructive The University of Texas System Michael Kolodziej, M.D. working relationship with your organization. Aetna
Howard McLeod, Pharm.D. However, we are very concerned that the comment period of only five business days Moffitt Cancer Center for the non-small cell lung cancer (NSCLC) scoping document makes it impossible Michael Pellini, M.D. for us to provide meaningful input. As a broad-based coalition, we have the Foundation Medicine opportunity to gain in-depth insight from a range of disciplines, and must also Kimberly J. Popovits balance the perspectives and needs of our members. Lung cancer is an Genomic Health Lori M. Reilly, Esq. extraordinarily complex disease, and the science supporting diagnosis and treatment PhRMA of NSCLC is moving at a rapid pace. It is impractical for many stakeholders, Hakan Sakul, Ph.D. particularly coalitions like PMC, to fully understand and respond to the scoping Pfizer Inc. document in such a short period of time. Jared N. Schwartz, M.D., Ph.D. Jared N. Schwartz, M.D., Ph.D., LLC The landscape of treatment options has undergone an astonishing evolution over the Michael Vasconcelles, M.D. past decade. Although patients and physicians once had few treatment options to Unum Therapeutics Jay G. Wohlgemuth, M.D. choose from, they can now take advantage of many targeted therapies that attack Quest Diagnostics specific mutations expressed by their cancer. Many lung tumors are now profiled using genomic analysis, which provides the treating physician with the information she needs to make individualized treatment choices. Finally, based on the growing body of clinical evidence, FDA is actively updating currently marketed therapeutics with biomarker information, moving them from the back-line to the front-line of care when paired with a diagnostic.
Public Policy | p. 11 Given the significant attention ICER’s assessments receive and the recent proposal by CMS to rely on ICER’s value standards in the Part B payment demonstration, we believe ICER has a responsibility to allow additional time for stakeholders to provide thorough, thoughtful feedback on the scoping document, as well as the draft evidence report. Therefore, we suggest that you give the public 30 or 60 days with no limit on response length to reply to both the scoping document and the draft evidence report. This timeline is consistent with those provided by federal agencies like FDA and CMS.
We appreciate your consideration of these issues, and would greatly value the opportunity to discuss them further and answer any questions you may have as you consider this important issue. If you have questions about this comment letter or would like to reach us, please contact Amy Miller, Ph.D., at 202-589-1769 or by e-mail at [email protected].
Sincerely yours,
Edward Abrahams President
2 Public Policy | p. 12
September 12, 2016 BOARD OF DIRECTORS President Edward Abrahams, Ph.D. Chair Institute for Clinical and Economic Review William S. Dalton, Ph.D., M.D. Two Liberty Square, Ninth Floor M2Gen Vice Chair Boston, MA 02109 Stephen L. Eck, M.D., Ph.D. Astellas Pharma Global Development Treasurer By electronic delivery D. Stafford O’Kelly Altan Pharma, Ltd. Secretary Re: Proposed Process Improvements to ICER’s Value Assessment Framework Amy P. Abernethy, M.D., Ph.D. Flatiron Health Dear Dr. Pearson: Past President & Chair J. Brian Munroe Endo Pharmaceuticals I am writing on behalf of the Personalized Medicine Coalition (PMC) in response to Bonnie J. Addario Bonnie J. Addario Lung Cancer ICER’s recent call for suggestions on how to improve its value assessment Foundation framework. Steven D. Averbuch, M.D. Bristol-Myers Squibb Company Paul R. Billings, M.D., Ph.D. PMC is comprised of more than 240 member institutions representing a wide range Biological Dynamics, Inc. of stakeholders, including patient groups, provider groups, payers, health care William W. Chin, M.D. delivery organizations, diagnostic and pharmaceutical manufacturers, and clinical PhRMA laboratories. Our members work to address issues in science, business and policy Neil de Crescenzo that impact personalized medicine. Change Healthcare Donna Cryer, J.D. Global Liver Institute We appreciate the opportunity to respond to your call for proposed improvements to Tim Garnett, FRCOG, MFFP, FFPM ICER’s evaluation process. Below, we outline some improvements for that process Eli Lilly and Company Julie K. Goonewardene that would help ensure meaningful engagement with the scientific and research The University of Texas System communities. Our comments focus on the following five areas: Susan McClure Genome magazine 1. Open Comment Periods Howard McLeod, Pharm.D. Moffitt Cancer Center
2. Length of Comment Letters Michael Pellini, M.D. 3. Inclusion of Relevant Clinical Expertise Foundation Medicine Kimberly J. Popovits 4. Peer Review Genomic Health 5. Transparency in Stakeholder Engagement Hakan Sakul, Ph.D. Pfizer Inc. Jared N. Schwartz, M.D., Ph.D. Open Comment Periods Jared N. Schwartz, M.D., Ph.D., LLC Michael Vasconcelles, M.D. Unum Therapeutics PMC and its members have the ability to provide in-depth, technical insights on the Jay G. Wohlgemuth, M.D. Quest subject matter of ICER’s evaluations. As a coalition, any insights we offer must represent the interests of a range of disciplines and balance the perspectives and needs of our many members. Meanwhile, the field of personalized medicine is moving at an incredibly rapid pace. In this context, it is impractical for many
Public Policy | p. 13 stakeholders, particularly coalitions like PMC, to fully understand and respond to ICER’s complex and lengthy documents in a short period of time. In the past, the time length of ICER’s open comment periods have not allowed for meaningful input by impacted stakeholders.
The length of open comment periods should reflect the importance, length, and complexity of the items to which the community is responding. We appreciate the recent steps ICER has taken to extend its comment periods, and hope it will build on them by accepting our suggestions.
Recommendations
Allow 30 days for the community to respond to short, clear, single-issue documents such as draft scoping documents; allow 60 days for the community to respond to evaluations of single-therapeutic or therapeutic-class reviews; allow 90 days for the community to respond to complex requests such as changes to methodology, the public-engagement process, the evaluation process, or draft evaluations that cover multiple drug classes and diagnostic trajectories. Holidays should be avoided.
Length of Comment Letters
Page limits for comment letters discourage thoughtful engagement with ICER. For example, the 185- page non-small cell lung cancer draft evidence report considers four populations, four interventions, four comparators, and a variety of outcomes. The subject matter of that document is also complicated by rapid scientific advancements and increased use of diagnostics. While innovators will rightly focus on their products, patient groups, professional societies, coalitions and others may want to respond to all aspects of the report. Removing page limits, like ICER has done with this call for suggestions, will allow for more descriptive contributions to ICER’s process.
Recommendation
To encourage feedback that mirrors the thoughtfulness and complexity of the documents in question, we urge ICER to discontinue the use of page limits for comment letters.
Inclusion of Relevant Clinical Expertise
Personalized medicine is a fast-moving and complicated field. Targeted therapies are coming to market regularly while, concurrently, FDA is updating labels to expand or target the use of certain drugs based on new clinical research results. This leads to rapid changes in how clinicians diagnose and prescribe targeted therapies. It is imperative that ICER’s evidence reports reflect the reality of how clinicians are currently using personalized therapies and accompanying diagnostics to diagnose and treat patients.
2 Public Policy | p. 14 Recommendations
To ensure that value assessments are relevant to current clinical realities and consistent with the movement towards personalized medicine, ICER should engage experts with disease-specific expertise. Stakeholders with relevant expertise should be represented on advisory panels reviewing ICER’s draft evidence reports, and their feedback should be considered before work products are finalized.
Peer Review
Peer review allows stakeholders with expertise and experience in a specific field of medicine to engage with ICER. Peer review also assures the public that ICER’s materials are scientifically and clinically valid. Submitting evidence reports for peer review after the report has already been released publicly for use in making health care decisions is not sufficient. ICER’s evidence reports should undergo thorough peer-review by an unbiased group of experts prior to their publication.
Recommendation
To ensure that ICER’s value assessments reflect the current state of science and clinical practice, ICER should develop and implement a peer review process that provides an opportunity for experts in appropriate fields who are not otherwise part of the evaluation process to review its work products.
Transparency in Stakeholder Engagement
Many stakeholders are positioned to provide valuable insight on value assessments. We commend ICER for publishing those insights and encourage the organization to continue to do so. However, stakeholders would greatly benefit from understanding how ICER sets its priorities and incorporates the feedback it receives. Engaging stakeholders in ICER’s process for setting priorities and making stakeholder comments (for draft scoping documents and evidence reports) publicly available alongside an explanation as to why ICER does or does not address the individual comments would greatly enhance the public engagement process and improve the impact that ICER’s value assessments have on the field.
Recommendations
ICER should ensure that feedback on all ICER materials, including scoping documents and evidence reports, is publicly available. Additionally, ICER should explain why stakeholder feedback is incorporated or not incorporated and engage the public while setting its priorities.
3 Public Policy | p. 15 Thank you again for issuing a call for suggestions about ICER’s value assessment process. While PMC has commented only on general process improvements, many of our members have provided detailed suggestions. We request that you consider those suggestions.
We hope this is the first step in public engagement on this topic and we look forward to working with you to improve ICER’s process so that the principles of personalized medicine are incorporated into its work. If you have questions about this comment letter or would like to reach us, please contact me by phone at 202-589-1769 or by email at [email protected].
Sincerely yours,
Amy M. Miller, Ph.D. Executive Vice President
4 Public Policy | p. 16
October 14, 2016 BOARD OF DIRECTORS President Edward Abrahams, Ph.D. Chair Robert M. Califf, M.D. William S. Dalton, Ph.D., M.D. U.S. Food and Drug Administration M2Gen Division of Dockets Management Vice Chair Stephen L. Eck, M.D., Ph.D. 5630 Fishers Lane, Room 1061 Astellas Pharma Global Development Rockville, MD 20852 Treasurer D. Stafford O’Kelly Re: Docket No. FDA-2016-D-1703 Altan Pharma, Ltd. Secretary Amy P. Abernethy, M.D., Ph.D. Principles for Codevelopment of an In Vitro Companion Diagnostic Device With a Flatiron Health Therapeutic Product Past President & Chair J. Brian Munroe Endo Pharmaceuticals Dear Dr. Califf: Bonnie J. Addario Bonnie J. Addario Lung Cancer Foundation The Personalized Medicine Coalition (PMC) appreciates the opportunity to submit Steven D. Averbuch, M.D. comments regarding the U.S. Food and Drug Administration (FDA)’s draft guidance Bristol-Myers Squibb Company document, Principles for Codevelopment of an In Vitro Companion Diagnostic Device with Paul R. Billings, M.D., Ph.D. Biological Dynamics, Inc. a Therapeutic Product. William W. Chin, M.D. PhRMA PMC, representing innovators, scientists, patients, providers, and payers, promotes the Neil de Crescenzo Change Healthcare understanding and adoption of personalized medicine concepts, services, and products to Donna Cryer, J.D. benefit patients and the health system. Global Liver Institute Tim Garnett, FRCOG, MFFP, FFPM Eli Lilly and Company Personalized medicine is an emerging field that uses diagnostic tools to identify specific Julie K. Goonewardene biological markers, often genetic, that help determine which medical treatments and The University of Texas System procedures will work best for each patient. By combining this information with an Susan McClure Genome magazine individual’s medical records, circumstances, and values, personalized medicine allows Howard McLeod, Pharm.D. doctors and patients to develop targeted treatment and prevention plans. Moffitt Cancer Center Michael Pellini, M.D. Foundation Medicine Our members have long had interest in the topic of how FDA will coordinate review of Kimberly J. Popovits targeted therapeutic products and the diagnostic tests that support their use. We commend Genomic Health FDA on this work and for engaging a diverse set of stakeholders and incorporating their Hakan Sakul, Ph.D. Pfizer Inc. various perspectives into this developing draft over the past decade. Jared N. Schwartz, M.D., Ph.D. Jared N. Schwartz, M.D., Ph.D., LLC Since the agency published its 2014 final guidance on the regulation of in vitro companion Michael Vasconcelles, M.D. Unum Therapeutics diagnostic devices, PMC has urged FDA to publish a detailed guide to aid product sponsors Jay G. Wohlgemuth, M.D. in coordinating the review of drugs and diagnostic products. We are pleased that FDA Quest responded to that suggestion with an outstanding draft on the topic.
This guidance is especially important now given that nearly one-third of FDA’s new drug approvals are personalized medicines. We expect that trend, which is already having a
Public Policy | p. 17 tremendous impact for patients, to continue. These advances are enabling more accurate diagnoses, better prediction of individual susceptibility to disease based on genetic or molecular factors, improved detection of disease at early stages, greater use of targeted treatments, and, more broadly, greater efficiency and effectiveness for the health care system.
Scope and Statement of Neutrality
These comments focus on novel therapeutic and diagnostic products that are being developed and regulated simultaneously. PMC responded separately to FDA's recent draft guidance documents on next-generation sequencing (NGS). Furthermore, the draft guidance document addresses the rather new concept of “complementary diagnostic.” While this concept is compelling, we will not address it in this letter other than to suggest that it might be considered as a topic for another draft guidance focused on that topic specifically. We also will not comment on the different types of medical devices outside of diagnostic testing nor will we comment on issues pertaining to the regulation of laboratory-developed tests. Finally, many of PMC’s members will present their own responses to the agency and will actively advocate for those positions. PMC’s comments are designed to provide feedback so the general concept of personalized medicine can advance. These comments are also intended to support and augment comments made by our members.
In this letter, PMC will identify areas where FDA could provide more detail through examples, points that FDA could clarify, and where terms should be defined.
Areas Where Examples Would Be Helpful:
Timelines: FDA urges both therapeutic and diagnostic product sponsors to meet with the appropriate FDA review centers while planning, and before launching, a clinical trial designed for regulatory purposes. Perhaps FDA could develop a hypothetical example and publish a sample timeline to aid sponsors. Such a timeline could allow therapeutic and diagnostic partners to work together in a timeline consistent with FDA’s expectations. It would also be helpful if the timeline allowed for multiple partners on drug or diagnostic development.
Prescreening: In the field of personalized medicine, physicians and medical centers often use advanced diagnostic tests to determine treatment paths for patients. Many patients consider clinical trials only after receiving those test results. Thanks to the increased use of NGS testing for treatment selection, this trend is growing. Because of this transformation in health care, prescreening is likely to be a factor in a clinical trial for a new targeted therapeutic. We suggest FDA develop a hypothetical example on how sponsors should manage designing, populating, and conducting clinical trails where prescreening is a factor. This may include approaches to analyzing data in a study where prescreening has occurred.
Inter-center consultation: In the draft guidance document, FDA makes note that at times, communications will be shared between the different FDA centers and the sponsors of the therapeutic and diagnostic. To streamline product development and review, we suggest that the agency provide procedural details regarding under what circumstances, when and how the agency will share communications between the centers and product sponsors. It would be helpful if FDA elaborated on how the diagnostic and review teams at FDA will coordinate their respective reviews and provide feedback to sponsors. FDA suggests that both therapeutic and diagnostic
2 Public Policy | p. 18 representatives participate in reviews of the partner product. We also suggest that FDA coordinate reviews so that center representatives could be present at meetings with sponsors of both products.
Areas Where Clarification Would Be Helpful
In some instances, FDA's recommendations or suggestions on possible approaches are unclear to sponsors, and we encourage FDA to clarify subjective statements that have been highlighted by other commentators. Below, PMC outlines some examples of where clarification may be necessary.
Stratification and bridging studies: It is currently unclear what stratification by assay cut off trial design would look like. Perhaps the agency could outline some examples of acceptable trial design so that sponsors can better understand what characteristics an acceptable trial design might entail. Furthermore, it would be helpful to understand how the agency would like to establish the cut off for the IVD companion diagnostic in bridging studies.
Banked samples: According to the draft document, use of banked samples could be acceptable if they are from adequate, well-conducted studies, yet no details are provided. Perhaps the agency could provide some attributes of an “adequate” and “well-conducted” study so that trial designs provided to the agency would better conform to expectation.
Areas Where Term Definitions Would Be Helpful
The terms “candidate IVD,” “early prototype test,” and “precursor IVD,” are all used throughout the draft guidance document. If those terms are meant to be synonyms, it would be helpful to use consistent terminology in the final guidance document. However, if they refer to IVDs in different stages of development or refer to different tests, it would be helpful to define each term. Throughout the document some other terms are not defined. Consistent and clear use of language will aid the coordination of regulatory review of diagnostic and therapeutic products. We suggest FDA provide a list of terms with definitions in an appendix or in footnotes. Please include the following: analytical studies, ICD, investigational plan, investigator role, protocol.
Conclusions/Recommendations
This draft guidance document provides a useful, thoughtful, and well-constructed guide to the codevelopment of drugs and diagnostics. PMC recognizes and appreciates that the process described in the draft guidance document could drastically improve the ease of coordination for codevelopment. Furthermore, we appreciate the significant work and experience that went into the development of the document. Clearly, FDA has worked very hard to aid innovators in bringing new products to market. The impact on personalized medicine is quite clear.
Individual members of the PMC are likely to comment with specific suggestions that will assist them in bringing targeted therapies to market. Those detailed suggestions should be given careful consideration by the agency. If the agency received conflicting yet well reasoned suggestions, publishing a rationale for agency decisions in the supporting document would prove very helpful to product sponsors.
PMC appreciates the opportunity to provide these comments and complements and encourages stakeholder engagement by the agency. PMC and FDA are united by a shared goal of providing patients and health care
3 Public Policy | p. 19 providers with safe and effective technologies that will best serve the needs of patients. If you have any questions about the content of this letter, please contact me at [email protected] or (202) 589-1769. We look forward to further opportunities to provide feedback.
Sincerely yours,
Amy M. Miller, Ph.D. Executive Vice President
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Where We Agree When It Comes to Regulating Laboratory-Developed Diagnostics
Amy M. Miller, PhD; Executive Vice President; Personalized Medicine Coalition
The Last Word
Federal agencies have a long history of finalizing regulatory documents at the end of an administration. If that history repeats itself in 2016, it may mean a new regulatory environment for an industry that includes more than 60,000 genetic testing products and services.
The FDA published a detailed proposal for regulating laboratory-developed tests (LDTs) in July 2014. The IN THE NEWS proposal was unpopular with most industry stakeholders for a variety of reasons, and Congress has indicated some interest in offering a legislative May 19, 2016 Public Policy | p. 21 solution to the issue. Meanwhile, the FDA has Two-pronged attack on maintained that it intends to finalize the document chemotherapy-resistant leukemia maintained that it intends to finalize the document chemotherapy-resistant leukemia this year, and the end of the Obama administration cells adds urgency to the endeavor.
Some observers speculate that an acceptable LDT May 18, 2016 regulation framework is out of reach for the An Early Look at Research From the diagnostics community, but that may not be true. 2016 ASCO Annual Meeting
At the beginning of this year, I moderated a series of May 18, 2016 discussions on potential legislative solutions with Drug against breast cancer is also representatives from the entire diagnostics highly potent against a frequent community, including those with an interest in form of leukaemia personalized medicine. During our discussions, it became clear that the community agrees that a solution to LDT regulation should take a risk-based May 17, 2016 approach to: Improving natural killer cancer therapy: Study 1. Protect public health labs. Public health labs should be protected by any regulatory paradigm, which means that sentinel, infectious disease, and public health labs must be able to design, deploy, READER'S POLL and use rapidly developed diagnostics to address critical public health needs. Do you think critically ill patients 2. Allow flexibility and efficiency when managing should have the right to try modifications. As diagnostic device developers have experimental drugs not yet approved by the FDA? long argued, the way test modifications are managed by a regulatory system should be flexible Yes and efficient to allow diagnostic tests to evolve with the clinical science that underpins them. No Unsure 3. Mitigate regulatory burdens for government and industry. To reduce burdens on government and SUBMIT industry, regulatory agencies should recognize when certain safeguards are already in place. These mitigation strategies can help regulatory bodies keep pace with the rapidly evolving science of CONNECT WITH US personalized medicine diagnostic testing.
4. Design a grandfathering system for tests already on the market. Tech firm NextGxDx estimates that there are more than 60,000 personalized medicine diagnostics offered by about 300 labs, with another Public Policy | p. 22 8 to 10 coming to market each business day.1 To 8 to 10 coming to market each business day.1 To manage such an enormous workload, a regulatory agency must design a grandfathering system that will allow most tests to remain on the market unless there is a compelling reason to remove them.
5. Ensure regulatory burdens reflect testing volumes. Regulatory burden must reflect testing volume. For example, diagnostics designed for rare and unmet needs should be given careful and different consideration to ensure that tests are developed for micromarkets.
6. Accept valid scientific evidence for regulatory purposes—even if that evidence does not include data from a randomized controlled trial. Personalized medicine challenges how healthcare products and services are conceived, developed, regulated, covered, paid for, and used by physicians. Evidentiary requirements for regulatory review must also evolve. The community agrees that regarding diagnostics, valid scientific evidence should be acceptable for regulatory review, even when that evidence does not include data from randomized controlled trials.
Personalized medicine depends on diagnostics, and reducing uncertainty about possible regulatory changes for them is essential to the field. Any proposal to alter the current regulatory landscape will be judged according to the characteristics outlined above. Reference 1. NextGxDx. How Many Genetic Testing Products Are There (#PMWC16)? https://blog.nextgxdx.com/2016/01/24/how- many-genetic-testing-products-are-there-pmwc16- infographic/. Accessed October 31, 2016.
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8. Science Policy
Strategies for Integrating Personalized Medicine into Health Care Practice
Daryl Pritchard[1], Franziska Moeckel[2], Marysusan Villa[3], Laura Housman[4], Catherine McCarty[5],
and Howard L. McLeod[6]
[1] Personalized Medicine Coalition, Washington, DC. [2] Inova Health System, Falls Church, VA. [3]
University of Pennsylvania Health System, Philadelphia, PA. [4] Molecular Health, Boston, MA. [5]
Essentia Institute of Rural Health, Duluth, MN. [6] Moffitt Cancer Center & Research Institute, Tampa,
FL.
Abstract
Aim: We identify common challenges to the clinical adoption of personalized medicine and provide strategies for addressing these challenges. Methods: Our team developed a list of common challenges through a series of group discussions, surveys, and interviews, and convened a national summit to discuss solutions for overcoming these challenges. We used a framework approach for thematic analysis. Results: We categorized challenges into five areas of need: (1) education and awareness; (2) patient empowerment; (3) value recognition; (4) infrastructure and information management; and (5) ensuring access to care. We then developed strategies to address these challenges. Conclusion: In order for health care to transition into personalized medicine, it is necessary for stakeholders to build momentum by implementing a progression of strategies.
Keywords
Integration into health care, clinical adoption, personalized medicine education, patient empowerment, value determination, information management, access to care.
Introduction
1 Science Policy | p. 1
Personalized medicine is an evolving field in which physicians use diagnostic tests to identify specific biological markers, often genetic, that help determine which medical treatments and procedures will work best for each patient. By combining this information with an individual’s medical records and circumstances, personalized medicine allows doctors and patients to develop targeted treatment and prevention plans.[1,2] While there are many alternative terms for personalized medicine, including precision, individualized and stratified medicine, this report does not distinguish between those terms or attempt to reconcile differing definitions of each. Rather, the term personalized medicine is used throughout the report to describe the concept as defined above.
Research and innovation in personalized medicine as it is defined here are extensive and expanding, as measured by the number of scientific publications and a documented emphasis on genetic testing, health information collection and management, biomarker discovery, and targeted therapies.[3,4] The molecular diagnostics market is growing rapidly and diversifying. A recent report by
NextGxDx estimated that nearly 4000 new diagnostic tests have been introduced to the market in
2015.[5] The same can be said for the molecular therapeutics market. In fact, 28 percent of all the medicines the U.S. Food and Drug Administration (FDA) approved in 2015 were personalized medicines,[6] and a recent study sponsored by the Personalized Medicine Coalition (PMC) and conducted by Tufts University demonstrates that 42 percent of all medicines and 73 percent of cancer medicines in development are potential personalized medicines.[7]
However, despite the steady increase in the number of clinically useful molecular diagnostics and targeted therapies, the health care system has been slow to integrate personalized medicine into clinical practice.[8-10] Indeed, evidence suggests that in most cases, personalized medicine is not even discussed at the point of care. A recent public survey has shown that only four out of 10 consumers are aware of personalized medicine, and only 11% of patients say their doctor has discussed or recommended personalized medicine treatment options to them.[11] Behind this lag in clinical
2 Science Policy | p. 2
adoption are novel challenges that health care delivery systems are encountering as they adapt to the new requirements, practices, and standards associated with the field.[12]
Background
Since the completion of the Human Genome Project in April 2003, there has been an increasing focus on genomics in medicine, coupled with efforts to help incorporate genomics information into health care practice. The United States Centers for Disease Control (CDC) established the Evaluation of
Genomic Application in Practice and Prevention (EGAPP) program in 2005 to evaluate genetic tests and other applications of genomic technology in transition from research to health practice.[13] The Human
Genome Research Institute’s Implementing Genomics in Practice Network (IGNITE) addressed barriers to the integration of genomics into medicine and offered potential solutions,[14] and the Electronic
Medical Records and Genomics Network (EMERGE) has addressed the uptake of genetic information in electronic health record systems for genomic discovery and genomic medicine implementation research.[15] The Clinical Genomics (ClinGen) Resource is currently developing interconnected community resources to improve understanding of genomic variation and its use in clinical care.[16] At the National Academy of Sciences, Engineering, and Medicine, an Institute of Medicine Roundtable on
Translating Genomic-Based Research for Health issued workshop reports on Integrating Large-Scale
Genomic Information into Clinical Practice[17] and Genomics-Enabled Learning Health Care Systems:
Gathering and Using Genomic Information to Improve Patient Care and Research.[18] Clinical adoption of personalized medicine is advancing globally. For example, the Personalized Medicine 2020 and
Beyond Strategic Research and Innovation Agenda (PerMed SRIA) included the development of an index of barriers for the implementation of personalized medicine and pharmacogenomics in Europe.[19]
Most recently, the PharmGKB and the Pharmacogenomics Research Network established the international Clinical Pharmacogenetics Implementation Consortium (CPIC) to help develop updated pharmacogenomics clinical practice guidelines,[20]
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While these programs have facilitated a dialogue about how to incorporate genomic information into health care practice, recent surveys show that most health care organizations are unprepared to implement personalized medicine,[21] and some hospital systems may be putting implementation programs on hold.[22] The barriers often involve knowledge gaps, system-wide process obstacles, and a resistance to the cultural changes necessary to move toward a more personalized care paradigm. Often, personalized medicine programs are working in isolation and, therefore, are not benefitting from the experiences of other health care delivery organizations.
PMC’s Health Care Working Group (HWG) has identified common challenges involved in developing personalized medicine programs and the most promising strategies for addressing them.
This article describes this initiative, which has provided a forum for health care delivery organizations to discuss integration of personalized medicine into clinical practice, highlighted basic principles, identified integration challenges, developed corresponding strategies to address challenges, and outlined a roadmap to help foster cultural change in medical practices.
Methods
PMC’s Health Care Working Group
PMC’s HWG is comprised of representatives from 49 organizations involved in health care delivery, including 19 academic health centers, 12 community health care systems, 16 health care delivery support organizations, and two physician groups (Supplemental Material 1).
PMC conducted a survey of the HWG regarding concerns and challenges related to the development and implementation of personalized medicine strategies in clinical practice. From that survey the group developed a set of principles and a list of significant common challenges encountered by health care delivery organizations. PMC then conducted semi-structured interviews with senior executives to provide detail and distinguish priority challenges faced by providers of all types. The group
4 Science Policy | p. 4
reviewed and revised the principles and list of challenges through a series of teleconference discussions.
Finally, PMC used a framework approach of qualitative research for thematic analyses.
Solutions
PMC coordinated a series of focus group discussions to discuss potential solutions for addressing the identified common challenges. The sessions included three separate discussions representing different stakeholders — providers (17 participants), industry (23 participants), and patients (14 participants).* Each group answered a series of questions about strategies for addressing common challenges (see supplementary material 2 for a list of focus group questions). From the responses, PMC developed a list of strategies to tackle each challenge. Alongside its partner, the Biotechnology
Innovation Organization, PMC then hosted a national meeting — Solutions Summit: Integration of
Personalized Medicine into Health Care — on October 14, 2015,** to discuss and refine the list of solutions.
Results
Members of the HWG broadly reported that health care delivery systems are encountering novel challenges as they adapt to the new requirements and practices associated with personalized medicine. They identified five general areas of challenges:
1. Education and awareness
2. Patient empowerment
3. Value recognition
4. Infrastructure and information management
5. Ensuring access to care
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The group developed five principles for integrating personalized medicine into health care that correlate with each of these areas (Box 1). Various previous efforts to better understand and prioritize challenges to integrating personalized medicine into health care have identified similar categories. For example, in
Europe and Canada, the PerMed SRIA categorized barriers to clinical adoption in the areas of (1) stakeholder involvement, (2) standardization, (3) interoperable infrastructure, (4) healthcare system, (5) data and research, (6) funding, and (7) policy making. [23]
Certain obstacles are particularly common among health care delivery organizations. The HWG identified the most significant of these and assigned them to five categories corresponding with the five identified areas of need (Table 1). It is noted that the perspective, scope, and magnitude of specific integration challenges sometimes differ between distinct types of health care delivery organizations, such as academic health centers and community hospitals. Thus, the HWG did not prioritize individual challenges, but rather emphasized that all of the common challenges are significant barriers to the integration of personalized medicine into clinical practice and identified the overarching priority as recognizing and addressing the need for a paradigm shift from traditional practice to personalized medicine.
Table 2 lists strategies organizations have implemented in part or in full to overcome the integration challenges. Organizations believe these strategies should be expanded nationally. The solutions are listed in categories corresponding with the five general areas of need. However, more specific descriptions of challenges were necessary to help provide clearer direction for potential action on particular solutions. These strategies are not meant to imply that health care delivery organizations must act alone in their implementation. On the contrary, many of the strategies involve developing evidence, building resources, and/or partnering on policy activities with multiple stakeholder groups.
The need for these collaborative solutions reflects perceived shortcomings of the current medical
6 Science Policy | p. 6
practice paradigm in which separate institutions advance priorities independently. These strategies thereby underline the need for a new paradigm.
Discussion
The evolution of health care delivery to personalized medicine requires making new knowledge available, placing a greater emphasis on patient perspectives, recognizing the value of molecular pathways in guiding care, building new infrastructure and information management processes, and reshaping health care delivery to ensure access to personalized medicine technologies and services.
Overcoming challenges in these areas will likely require near-term strategies to implement programs that are straightforward and can provide clear solutions as well as long-term strategies that can drive systemic and cultural change. However, with a clear understanding of the set of challenges, and the best strategies for overcoming those challenges, a roadmap for health care systems to advance the personalized medicine paradigm can be built.
1. Education and Awareness
Perhaps the greatest challenge to integrating personalized medicine into health care is a lack of education and awareness among patients and throughout the health care delivery community. The path forward in this area, however, might be the clearest and most straightforward. Freely available educational resources that provide necessary basic scientific explanations of personalized medicine principles as well as technology-specific details have been and are being developed by a number of organizations.[24-28] When published online, these materials can be presented in multiple formats based on the needs of different stakeholders. However, they must be accurate, trusted, and updated regularly. PMC continues to work with the personalized medicine community to develop a content-rich website that can serve as the “go-to” source for personalized medicine knowledge.[29] Other strategies to address education challenges include coordinating community forums to agree upon a common
7 Science Policy | p. 7
terminology regarding personalized medicine and to engage community leaders as well as patient support groups and health care delivery professionals to help promote personalized medicine and disseminate educational materials.
Although many community education strategies are clear, building awareness and knowledge will not be easy, especially with regard to physicians and other health care providers. In-person training and educational programs led by genetic experts can be made available to help ensure that provider knowledge is up to date regarding personalized medicine, and current medical and pharmacy school curricula can be updated to reflect current medical concepts. While reaching an adequate level of awareness and education among all stakeholders will take time, strategies to address these challenges are straightforward and ready for implementation.
2. Patient Empowerment
As we move forward, patients can be fully informed, both in terms of options for prevention or treatment of disease and efforts to protect their molecular information from being used in ways that would cause them concern, and, perhaps, long-term repercussions, such as discrimination, job loss, or loss of health insurance coverage. Patients can be involved in deciding how their data is used, particularly in an environment where care is managed across a number of specialized physicians (i.e., oncologist, cardiologist, rheumatologist, et al).
In these areas too, the way forward seems clear. Many health and research organizations in the public and private sectors are reconsidering current policies related to patient privacy and consent for the use of molecular information, such as the development of updated recommendations and policies on informed consent for participation in clinical research.[30-32] Some providers are developing genetic counseling service policies to ensure that patients, early in their care, are able to understand their individual molecular information and its implications, so that they are able to make informed
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decisions regarding its disclosure and use before problems arise.[33-35] Additionally, programs are being developed or are ready to be implemented that will establish the necessary partnerships among industry suppliers, providers, and patients and their families to ensure patient data is presented in ways that are meaningful and useful to each of these groups. Perhaps most importantly, practitioners are recognizing that they need to regularly and appropriately involve patients in their ongoing health care decision-making.[36] Indeed, practitioners are increasingly recognizing that they have a duty to do so.
Health systems can provide the necessary educational and consultation support that makes that possible, and information systems can be designed to ensure an appropriate role for patients.
3. Value Recognition
While many stakeholders believe that personalized medicine can provide benefits to patients and the health care system, payers and providers are often reluctant to change policies and practices without convincing evidence of clinical and economic value.[37] It is not clear how that evidence should be developed and disseminated for maximum impact. It is also not clear to health care delivery organizations how to develop profitable business models to support and sustain the delivery of personalized medicine.
However, strategies to include financial, practice process, and risk reduction endpoints within the body of evidence, in addition to patient survival and disease progression information, have begun to emerge and are much needed. Forums between payers and product developers, for example, may facilitate a better understanding of the evidence requirements necessary for positive coverage determinations. When generating evidence reports, product manufacturers can customize them for different audiences, such as payers, providers, and clinical guideline developers. However, the personalized medicine value proposition increasingly depends on provider evidence generation.
Providers decide which products and services to use and frequently must negotiate with payers to
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procure insurance coverage. The evidence that payers require to make coverage determinations for diagnostic tests is increasingly generated through analysis of clinical practice data. Thus, providers may consider collaborating directly with manufacturers and payers as part of a three-pronged approach to value determination.
To help facilitate an understanding of how personalized medicine can affect patient care, providers can establish proactive policies that incentivize practitioners to optimize treatments based on individual patient characteristics. However, as with insurance coverage, the facilitation of incentives for the delivery of personalized treatments will likely require practice-based evidence about their value.
The need for evidence to facilitate policies that allow greater access to personalized medicine, contrasted with the need for access policies that enable evidence generation, has led to a challenging conundrum in demonstrating the value proposition. Both payers and providers would benefit from the implementation of a learning health system that provides a universally accepted and user-friendly way to systematically collect and share treatment and outcomes data. Implementing a learning health system would benefit from effective information management systems to aggregate and easily share clinical data for all patients, so as to analyze common patterns.
4. Infrastructure and Information Management
Effectively managing the massive amounts of information associated with personalized medicine and coordinating programmatic processes and services related to its use are also major areas of need.
Many organizations are committed to overcoming challenges in these areas, but strategies need to be developed and implemented widely in order to have a meaningful impact on the larger health care system. Combining efforts can start by fostering a better understanding of different perspectives across stakeholder groups, encouraging more structured collaborations, and sharing experiences and best practices among health care organizations. Health care delivery organizations that have implemented
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personalized medicine programs and are working with information management organizations highlight the need for clear program leadership structures, effective processes for making programmatic decisions, and coordination of institutional personalized medicine program policies and processes across research and clinical programs. In consideration of this, improvements to electronic health records can be developed and implemented so that they include individual patients’ genetic information with built- in clinical support tools, describing potential clinical actionability. Biomarker and outcomes information can be standardized and interoperable across multiple health information technology platforms.
5. Ensuring Access to Care
Perhaps the most complex area of need is adapting health delivery approaches, processes, and service structures to ensure access to personalized medicine. In many cases, overcoming challenges in this area requires cultural change as well as the implementation of new programs. Progress will likely require the shifting of the perspectives of many stakeholders toward a personalized medicine paradigm, which can be accelerated by improving the knowledge base, empowering patients, demonstrating value across stakeholder groups, and building effective program infrastructure and information management processes. Traditional fee-for-service practices can sometimes provide incentives for providers to deliver increased service volumes rather than identifying the best interventions for particular patients.
Payer, provider, and patient-directed policies to promote cultural change, such as developing incentives for payers to cover novel personalized medicine technologies with value-based evidence accumulation and defining value in terms of patient outcomes, could help accelerate progress. Guidelines and clinical support tools that are focused on the best care for individual patients can be regularly updated to include personalized medicine concepts and practices. Other practical strategies needed to begin breaking down the cultural barriers to personalized medicine include removing disincentives for using new technologies that are of high value but are provided outside of network labs and making sure that professional fees for personalized medicine services and biomarker analysis are appropriate, both for
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the practitioner and the payer. Implementing these strategies will not suddenly change ingrained medical practice norms and culture, but will help contribute to an accelerating paradigm shift toward personalized medicine.
Study Limitations
The strategies and recommendations listed in this report are generalized to all U.S. health care delivery organizations and do not account for regional differences in care delivery or distinguish between academic health centers and community hospital systems. The primary differences between academic health centers and community hospitals are the availability of resources and the nature of institutional missions. Academic health centers often include both research and education in their missions, and often have endowments and/or research grants. In these settings, support of research activities is recognized as vital to the delivery of high quality health care. In contrast, community hospitals rarely include research and education in their missions, and there can be a tension between research endeavors and clinical care. In these settings, the research programs that do take place typically favor translational research that will benefit a specific patient population, and it can be difficult to attract external funding. Thus, it is important to consider the type of health care institution being evaluated when considering the strategies and recommendations presented here. For example, community hospital systems often ranked workforce education as a higher priority challenge than many academic health centers. Also, it is important to consider the regional context for the delivery of care.
The types of challenges and their magnitude of impact on the adoption of personalized medicine can differ between urban and rural settings. For example, in some rural areas, the lack of access to high- speed Internet continues to challenge education, e-learning, and e-health programs, and adoption lags behind Internet availability.[38] There is also a growing rural/urban divide on compliance with meaningful use requirements pertaining to medical records.[39] A description of specific case examples
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of various health care delivery organizations’ experiences in integrating personalized medicine into clinical practice might further elucidate these challenges.
The analysis of common challenges presented in this report is largely qualitative and is limited to discussion among participants in the HWG. The collective perspectives of the HWG members may differ from those of representatives at other health care delivery organizations. The analysis in this report consisted of polling members, informal survey, and consensus review, and did not account for differing perspectives within the HWG or measure the strength of agreement related to particular challenges. A survey targeting the broader health care delivery community and consisting of rankings of challenges might be able to provide quantitative analytics that could be used to better distinguish between differing perspectives of various types of health care delivery organizations.
Conclusion
As the health care system makes the transition from its traditional, one-size-fits-all approach toward a personalized medicine paradigm, it will be necessary to overcome challenges in several areas.
Some strategies involving activities, programs, and policies, such as those related to education and awareness and patient empowerment, can be implemented now or in the near term. Other strategies will require stakeholders to overcome reluctance to reshaping traditional practices and may require a cultural change in the way medicine is approached. However, progress made in addressing challenges in the areas where strategies are most straightforward and for which solutions are clearest should help increase our understanding of what is necessary to address more difficult challenges in other areas, thereby setting up a progression of solutions, ultimately fostering behavioral change that drives adoption of personalized medicine (Figure 2). For example, redesigning consent policies for the use of individual molecular data before problems arise and in a way that ensures patient privacy and data control could improve the process for collection and utilization of patient information for research and
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clinical care. Improved patient data processing would allow us to devise more effective strategies for community-wide information management, which could, in turn, help reshape medical practice approaches and processes.
Paradigm shifts requiring cultural change typically happen slowly and often face resistance.
However, when a new paradigm provides clear advantages, there is counter pressure to accelerate a shift in culture. In this context, we offer this report as a roadmap for the implementation of integration strategies to add more momentum toward effecting cultural change and a paradigm shift toward personalized medicine.
Future perspectives
Currently, several health care delivery organizations are actively engaged in implementing personalized medicine programs. Understanding and communicating which policies and processes have worked best for these early adopters will help other organizations as they design and implement their own personalized medicine programs. This report highlights the need for a progression of strategic programs and efforts that encourage a paradigm shift. Implementation of these strategies uses a systems approach interfacing multiple disciplines including molecular biology, epidemiology, and public health.[40] Basic strategic components to support personalized medicine could help foster system-wide directives and incentives that will be key to driving cultural change.
The initial stages of implementing personalized medicine programs will involve putting into practice strategies to address education and patient empowerment challenges while, at the same time, setting up appropriate leadership and forums to design and initiate programs and policies that will drive value recognition and effective infrastructure and information management. Implementing these strategies can position health care delivery organizations to address challenges related to adapting
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treatment approaches and processes that will ensure access to personalized medicine and thereby continue to usher in a new era of medicine.
Executive Summary
Integration of Personalized Medicine • Despite the steady increase in the number of clinically useful molecular diagnostics and targeted therapies, clinical adoption has been slow. • Behind this lag in clinical adoption are novel challenges that health care delivery systems are encountering as they adapt to the new requirements, practices, and standards associated with the field. Education and Awareness • Healthcare providers, payers, employers, and policymakers, as well as patients and their families, need to have a better understanding of personalized medicine concepts and technologies. Patient Empowerment • Policies and practices related to patient engagement, privacy, data protections, and other ethical, legal, and societal issues regarding the use of individual molecular information must ensure appropriate consent and be acceptable to patients. Value Recognition • Best practices must be established for the collection and dissemination of evidence needed to demonstrate clinical utility of personalized medicine and ensure the recognition of its value to care. Infrastructure and Information Management • Effective healthcare delivery infrastructure and data management systems needs to be developed and applied so that individual patient and clinical support information is comprehensive, useful, and user-friendly, and so that it can be used to guide clinical decisions. • Processes for standardization of reported medical data, clinical support, and outcomes information need to be developed so that information is exchangeable across multiple health IT platforms. Access to Care • Best practices for health care delivery approaches, processes, and program operations that ensure access to personalized medicine must be established and implemented. • Practical strategies needed to begin breaking down the cultural barriers to personalized medicine for the practitioner and the payer. Roadmap for Integration • As the health care system makes the transition toward a personalized medicine paradigm, it will be necessary to overcome challenges in several areas. • Some areas of challenges can be addressed through activities, programs, and policies that can be implemented now or in the near term, while other areas will require a
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cultural change in the way medicine is approached. • Progress made in addressing challenges in education and patient empowerment can help accelerate strategies to overcome challenges in other areas, such as value recognition and information management. • As we increase our understanding of what is necessary to address more difficult challenges, there will likely be a progression of strategies, ultimately fostering behavioral change that drives adoption of personalized medicine.
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Box 1: Principles for Integrating Personalized Medicine into Health Care
Personalized medicine is a fundamental change in the way medicine is practiced and delivered. It strengthens prevention, diagnosis, and treatment efforts through customized therapies appropriate for each patient. In order to integrate personalized medicine into health care practice, the following principles should be considered:
1. Healthcare providers, payers, employers, and policymakers, as well as patients and their families, need to have a better understanding of personalized medicine concepts and technologies.
2. Policies and practices related to patient engagement, privacy, data protections, and other ethical, legal, and societal issues regarding the use of individual molecular information must ensure appropriate consent and be acceptable to patients.
3. Best practices must be established; for the collection and dissemination of evidence needed to demonstrate clinical utility of personalized medicine and ensure the recognition of its value to care.
4. Effective healthcare delivery infrastructure and data management systems should be developed and applied so that individual patient and clinical support information is comprehensive, useful, and user-friendly, and so that it can be used to guide clinical decisions.
5. Best practices for health care delivery approaches, processes, and program operations that ensure access to personalized medicine must be established and implemented.
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Table 1: Common Challenges to Integrating Personalized Medicine into Health Care
Awareness and Education
• Variable terminologies exist for personalized medicine, leading to confusion. • Consumer awareness is poor and demand for products and services is relatively low. o The science is complex and often difficult to correlate with various personalized treatment options. o Different consumers have different information needs and health literacy levels. • Awareness and knowledge within the health care provider community is insufficient. o Knowledge resources are scarce, seldom used, and are not regularly updated. o Education efforts outside of oncology are uncommon. • Information on personalized medicine practices, policies, and community support is not readily available, or not being used. • Workforce training for new technologies/techniques is insufficient. • Medical school curricula on integrating genetics/genomics are often outdated.
Patient Empowerment
• Patient consent policies for the use of molecular information are often confusing or inappropriate. • Molecular information is often not secure and may be subject to hacking. • Data sharing policies do not always take into consideration proprietary and privacy concerns. • Providers do not adequately involve patients in their health care decision-making, and do not account for the level that a patient wants to be engaged in health care discussions. o Patient preferences in treatment and prevention strategies are not always considered. • Patients and their families are often not appropriately counseled with regards to genomics. • Racial, ethnic, economic and regional disparities are not appropriately addressed.
Value Recognition
• It is unclear what evidence payers require to facilitate coverage. • Payment rates for diagnostics are often not based on their value to care. • Clinical and economic data demonstrating value are still emerging. • It is unclear what evidence is necessary to convince doctors to clinically adopt new technologies and services. o Not all molecular variants are clinically actionable. o Practice guidelines are slow to be updated. • Health care organizations do not recognize the value of integrating personalized medicine into the institution. o The return on investment (ROI) across the institution is not yet clear. o Programmatic value that may not have an immediate ROI is not well understood. • Preventive care is often overlooked in practice. • There are few incentives for sharing clinical data about individual variability and outcomes.
Infrastructure and Information Management
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• Personalized medicine programs lack clear decision-making processes. • Policies and processes are not always coordinated across the health care institution. o Communication across the continuum of care is insufficient or breaks down easily. o Molecular Information is not often coupled meaningfully within clinical support tools. o Research is not well-coordinated with clinical practice. o Policies to better evaluate program efficiency and to implement adjustments are lacking. o Laboratory services often operate in a silo. • It’s unclear what diagnostic tests can/should be run in-house vs. sent to external labs. • Source factors are often not appropriately considered when making decisions regarding buying vs. making diagnostic tests. o Projection of product volumes may be inaccurate considering new Dx and Rx needs. • Information technology systems/platforms are unable to effectively manage exceptionally large amounts of individual molecular information. • Molecular information collection, storage and analysis takes more time than many physicians feel it is worth. • Electronic health record information is not standards-based and usually not interoperable. Individual molecular data is not effectively translated into evidence for clinical care. • Biorepositories are often not effectively maintained or integrated with information systems.
Ensuring Access to Care
• Many high-value diagnostic tests or services are not covered by health insurance companies. • Traditional fee-for-service processes provide a system-wide incentive for ordering services based on volume rather than value. • Electronic health records do not easily incorporate genetic information. • Some physicians are reluctant to adopt personalized medicine practices. o There is a perception that personalized medicine techniques require time without adequate compensation. o There is a perception that it is too cumbersome to involve genetics experts/counselors in patient care. • Clinical guidelines do not reflect current concepts in personalized medicine. • Most clinical decision support tools are not equipped for integrating patient biomarker information in treatment decision-making. • Serious adverse events/FDA black box warnings related to targeted treatments are often misunderstood related to use in appropriate populations. • Medical groups, community health care organizations and other outside stakeholders are often not coordinated with regards to personalized medicine programs and guidelines. • Sustainable business models are yet to be developed. • Products and services are not always available, particularly in rural settings, and many patients are reluctant or unable to travel to other health centers. • Geneticists/genetic counselors/molecular pathologists are not always accessible, especially in rural settings.
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Table 2: Strategies for Overcoming Challenges to Integrating Personalized Medicine into Health Care Practice
Awareness and Education Challenge: Health care providers, payers, employers, and policy-makers, as well as patients and their families, often have a poor or impractical understanding of personalized medicine.
• Develop freely accessible online educational information that is presented in multiple formats based on the needs of different stakeholders. • Organize collaborative forums to develop and agree upon a common lexicon regarding personalized medicine. • Organize industry forums to develop and agree upon consistent themes for communications based on scientific evidence and value. • Provide health care professional groups and patient support organizations with personalized medicine information and educational materials, and actively manage multiple communication and dissemination channels. • Identify physician and community leaders to participate in regional events that raise awareness and promote personalized medicine. • Engage pharmacists to help patients understand the molecular mechanisms of their disease and the benefits of personalized medicine technologies. • Develop social media platforms to raise awareness of personalized medicine events, activities and new technologies. • Update the current medical and pharmacy school curricula to holistically integrate concepts related to personalized medicine. • Develop new personalized medicine Continuing Medical Education (CME) programs.
Patient Empowerment Challenge: Patients need to be proactively involved in their treatment decision-making,and in policy development related to information privacy, data protections and other ethical, legal, and societal issues.
• Include patient representatives in the development of proactive policies and practices related to patient protections and the use of individual molecular information. • Implement state-of-the-art cybersecurity measures related to individual molecular information. • Develop programs to explain diagnostic test results to patients; provide them with recommendations and easy access to related information and counseling. • Provide counseling services to patients before ethical dilemmas arise. • Incorporate patient-reported outcomes through multiple channels to capture and better understand patient experiences. • Design clinical trials with diverse research participants that include persons of various ethnicities, races, ages and genders to better inform the value of a specific treatment option for any given patient.
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Value Recognition Challenge: Payers and providers are unconvinced of the benefits of personalized medicine; evidence demonstrating its value to health care is still emerging.
• Provide a forum for payers and the diagnostic and biopharmaceutical industries to discuss the health technology assessment process and evidence requirements necessary for coverage. • Conduct economic impact studies that are meaningful to payers. • Design clinical studies to serve multiple purposes, including regulatory approval, establishing clinical utility for payers, and informing clinical guidelines; customize scientific and value-based evidence reports for different audiences (payer, provider, clinical guideline developers) based on their particular needs. • Develop standards as well as measurable targets for comparative effectiveness research studies and coverage with evidence development programs. • Design and implement research studies that demonstrate the cost and benefits of positive coverage decisions in areas of unmet need. • Develop and implement proactive policies that incentivize health care providers for optimizing treatments based on individual patient characteristics. • Include medical center and in-house provider laboratories in CMS median pricing determination for a fairer market value for diagnostic tests. • Facilitate a learning health system by developing an effective, universally accepted and user-friendly process to systematically collect and share treatment and outcomes data.
Infrastructure and Information Management Challenge: Health system infrastructure and information management is not yet well equipped for handling the massive amounts and different kinds of information associated with personalized medicine.
• Coordinate institutional policies and processes that assure effective communications through the continuum of care and across research and clinical programs, and develop an effective process for making programmatic decisions. • Include each patient’s individual genetic data, as well as information regarding clinically actionable variants, within electronic health records. • Assure that all medical data, clinical support and outcomes information is standardized and interoperable across multiple health IT platforms. • Develop and implement user-friendly platforms to input data and provide clinical support information to physicians in a way that saves time and resources. • Develop platforms that are easily customized for different clinicians based on the level of information that best suits them. • Assure that clinical support information includes complicating factors such as previously failed treatment classes and contra-indications and is provided within the electronic health record in a way that is easily recognized and accessed by physicians. • Incorporate adverse event reporting and link it to pharmacogenetic information on an individual and population-wide basis. • Develop proactive policies to incentivize data sharing and facilitate real-time data exchange for learning health systems.
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Ensuring Access to Care Challenge: Health care systems processes and procedures are optimized for traditional trial-and-error and fee- for-service practices resulting in disincentives for the use of personalized medicine products and services.
• Define incentives for payers to cover novel technologies with value-based evidence accumulation. • Develop policies that ensure clinical guidelines and support tools are focused on providing the best treatment strategies for individual patients and are regularly updated. • Develop policies that remove disincentives for using technologies that are high-value but are provided outside of network labs. • Ensure that professional fees for personalized medicine services and biomarker variant analyses are adequate. • Develop policies that ensure access to genetic analysis experts and counselors where appropriate (including virtual access when necessary) and that streamline the process for their inclusion in patient care. • Develop and implement a national approach to basket-studies/clinical trial enrollment based on molecular characteristics. • Include personalized medicine principles and practices in alternative payment and delivery models.
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Figure 1: Progression of Strategies by Area of Need for the Transition from Traditional Medical Practice to Personalized Medicine
Infrastructure Patient & Information Empowerment management Ensuring Access to Traditional Care Personalized Education & Medical Value Medicine Practice Awareness Recognition
Implementation Readiness
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Supplementary Material 1
Figure 1: PMC Health Care Working Group
2
16 19
12
Academic Health Center Community Health Care System Health Care Delivery Support Physician Group
Academic Health Centers: Community Health Care Systems: Baylor Health Care System Precision Medicine Institute Cancer Treatment Centers of America Cedars-Sinai Medical Center Catholic Health Initiatives Cleveland Clinic Center for Personalized Genetic Health Care Christ Hospital Indiana Institute for Personalized Medicine Essentia Institute of Rural Health Mayo Clinic El Camino Hospital MD Anderson Institute for Personalized Cancer Therapy Inova Health System Moffitt Cancer Center & Research Institute Intermountain Healthcare Ohio State University Knight Cancer Institute Marshfield Clinic University of Pennsylvania Health System Mission Health Roswell Park Cancer Institute Partners Health Care Rutgers Cancer Institute Sutter Health Stanford Clinical Genomics Center VA Medical Center, Dallas University of Alabama, Birmingham University of Florida Health Care Delivery Support Organizations: University of Pittsburgh Medical Center Ashion University of South Florida Biodesix University of Texas Biotechnology Innovation Organization Vanderbilt University Medical Center Counsyl Virginia Commonwealth University Health System Cure Forward Foundation Medicine Physician Groups: Flatiron Health Association for Molecular Pathology (AMP) Health Decisions CRO+ College of American Pathologists (CAP) Health Synergy Solutions, LLC Informed DNA MassiveBio Molecular Health Maine Dartmouth Family Medicine Registry N of One Syapse Inc. XIFIN
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Acknowledgements
The authors wish to acknowledge Phi Vu, Scott McGoohan, Paul Sheives, and Jeremy Isenberg, Biotechnology Innovation Organization, for their planning and research contribution to the Solutions Summit: Integration of Personalized Medicine into Health Care, held on Oct. 14, 2015, Washington DC, for which a component of this manuscript was based. We would also like to acknowledge Christopher Wells and Amy Miller, Personalized Medicine Coalition, and Marcia Kean, Feinstein Kean Healthcare, for their editorial contributions to the writing and revising of the manuscript.
The authors would also like to acknowledge the Members of the Personalized Medicine Coalition’s Health Care Working Group (HWG) for their participation in this study and review of the manuscript:
Edgar Staren, Ashion PMED Amy McGuire, Baylor Health Care System Precision Medicine Institute Robert Mennel, Baylor Health Care System Precision Medicine Institute Susan Zook, Cancer Treatment Centers of America Damon Hostin, Catholic Health Initiatives Jeffrey Otto, Catholic Health Initiatives Dermot McGovern, Cedars Sinai Medical Center Ian Wright, Cedars Sinai Medical Center Philip Leming, Christ Hospital Kenneth Nesmith, Counsyl Martin Naley, Cure Forward Lynn Dowling, El Camino Hospital Alexis Carter, Association for Medical Pathology Amy Abernethy, Flatiron Health Susan Hager, Foundation Medicine Steve DeChearney, Health Decisions CRO+ Jake Chen, Indiana Institute of Personalized Medicine Jamie Renbarger, Indiana Institute of Personalized Medicine David Nixon, Informed DNA Amjaad Al-Hussain, Inova Health System Marshall Ruffin, Inova Health System Lincoln Nadauld , Intermountain Healthcare Murray Brilliant, Marshfield Clinic Selin Kurnaz, MassiveBio Gianrico Farrugia, Mayo Clinic Sam Smith, Mayo Clinic Scott Beck, Mayo Clinic Dr. Funda Meric-Bernstam, MD Anderson Kenna Shaw, MD Anderson Lynn Dressler, Mission Health Todd Kneppler, Moffitt Cancer Center & Research Institute Jennifer Levin Carter, N of One Greg Feero, National Institutes of Health
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Brian Druker, Oregon Health & Science University Knight Cancer Institute Joseph Carroll, Oregon Health & Science University Knight Cancer Institute Scott Weiss, Partners HealthCare Center for Personalized Genetic Medicine David Roth, Penn Medicine, University of Pennsylvania Health System Candance Johnson, Roswell Park Cancer Institute Lorna Rodriguez, Rutgers Cancer institute James Ford, Stanford Clinical Genomics Center Jane Binger, Sutter Health Andro Hsu, Syapse Inc. Jonathon Hirsch , Syapse Inc. Dennis Hansen, Health Synergy Solutions, LLC Nita Limdi, University of Alabama, Birmingham Larisa Cavallari, University of Florida Larry Lesko, University of Florida Agnieszka Swiatecka-Urban, University of Pittsburgh Medical Center Jeremy Berg, University of Pittsburgh Medical Center Steven Shapiro, University of Pittsburgh Medical Center Scott Steele, University of Rochester Stephen Liggett, University of South Florida Julie Goonewardene, University of Texas Dan Roden, Vanderbilt University Medical Center Robin North, Vanderbilt University Medical Center Richard Pollack, VCU Health System Rina Wolf, Xifin
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Supplementary Material 2:
Focus Group Discussion Questions:
Provider Focus Group: September 15, 2015
1. What is necessary to ensure that providers understand personalized medicine concepts and are aware of, and willing to use, novel personalized medicine technologies as they are introduced into practice? What sources of information and types of evidence are most effective in communicating to providers about developments in, and encouraging adoption of, personalized medicine tools?
2. Over the past few years, how has evidence required for utilization of personalized medicine products within your health center changed, if at all?
3. Is the value of most personalized medicine products clear and demonstrable? How does your organization define “value” in the context of personalized medicine approaches, or medical products in general, for use in clinical practice?
4. How can we best integrate personalized patient data into a resource to enable providers to successfully use appropriate, precise, timely, and clinically actionable patient information to improve patient care, and also facilitate continuing research into not yet clinically actionable data points?
5. What can the industry and other stakeholders do to better educate provider populations on the concept of personalized medicine?
Industry Focus Group: September 11, 2015
1. Over the past few years, how has the environment related to the evidence required for reimbursement and clinical adoption of personalized medicine products developed by your company changed, if at all?
2. What can the various stakeholders (industry, providers, payers) do to better educate provider and patient populations about personalized medicine?
3. What is necessary to build recognition of the value of personalized medicine in a way that can facilitate uptake in health care delivery? What are appropriate incentives to encourage greater uptake of personalized clinical decision-making by payers and providers?
4. How can we better integrate personalized patient information into a resource that provides access to precise, timely, relevant patient information so that providers can utilize such information in their decision-making and patients can better understand and communicate their concerns?
5. Is the value of most personalized medicine products demonstrable? How does your organization define “value” in the context of personalized medicine approaches, or medical products in general, for use in clinical practice?
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Patient Focus Group: September 18, 2015
1. Over the past two years, has the environment changed relating to evidence and coverage of personalized medicine diagnostics affecting your patient population?
2. Outside of issues of regulatory and reimbursement, what barriers are preventing access for patients in your constituency?
3. What can the various stakeholders (industry, providers, payers) do to better educate patient populations on the concept of personalize medicine?
4. How does your organization define “value” in the context of personalized medicine approaches, or medical products in general, for use in your patient population?
5. Will increases in the affordability and availability of a patient’s genomic information empower patients to better their health or are you concerned that the complexity will confuse patients and result in inefficiencies in the system as they seek input from physicians?
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NOTES
* Focus group members participated on a volunteer basis. No compensation, nor individual or organizational attribution in this or any publication was provided.
** The Solutions Summit was sponsored in part by corporate and non-profit organization partners:
Alliance for Aging Research, AstraZeneca, CareDx, Foley Lardner LLP., Foundation Medicine, Johnson &
Johnson, The National Pharmaceutical Council, Novartis, Pfizer, and Vertex.
REFERENCES
[1] The Personalized Medicine Coalition. The Basics (2016). http://www.personalizedmedicinecoalition.org/Education/The_Basics
[2] The Personalized Medicine Coalition. The Case for Personalized Medicine (2014). http://www.personalizedmedicinecoalition.org/Resources/The_Case_for_Personalized_Medicine
[3] Novartis Oncology. The Precision Oncology Annual Trend Report: Perspectives from Payers,
Oncologists, and Pathologists (2016)
[4] Oxford Economics. Healthcare Gets Personal (2016). https://dam.sap.com/mac/preview/a/67/UmEUnxHHnJJzOOlUwAmnyXggPmAJJzgxUPAEmOXHxcwxPEP c/open20160412042800.htm
[5] NextGxDx. The Current Landscape of Genetic Testing (2016). https://www.nextgxdx.com/insights
[6] The Personalized Medicine Coalition. 2015 Progress Report: Personalized Medicine at FDA (2016). http://www.personalizedmedicinecoalition.org/Resources/2015_Progress_Report_Personalized_Medici ne_at_FDA [7] The Personalized Medicine Coalition, PhRMA. Biopharmaceutical Companies’
Personalized Medicine Research Yields Innovative Treatments for Patients (2015). http://www.personalizedmedicinecoalition.org/Resources/PMCPhRMA_Report_Biopharmaceutical_Co mpanies_Personalized_Medicine_Research
Science Policy | p. 29
[8] Aspinall MG, Hamermesh RG. Realizing the promise of personalized medicine. Harvard Bus Rev.
85(10), 108-117 (2007).
[9] Evans JP, Meslin EM, Marteau TM, Caufield T. Deflating the genomic bubble. Science. 331(6019),
861-862 (2011).
[10] ScienceDaily. Personalized medicine: moving forward slowly but surely (2008). https://www.sciencedaily.com/releases/2008/02/080211094056.htm
[11] Miller AM, Garfield S, Woodman RC. Patient and provider readiness for personalized medicine.
Personalized Medicine in Oncology. 5(4), 158-167 (2016).
[12] Manolio TA, Chisholm RL, Ozenberger B, et al. Implementing genomic medicine in the clinic: the future is here. Genet Med. 15(4), 258-267 (2013).
[13] Centers for Disease Control and Prevention Office of Public Health Genomics. About EGAPP (2013). http://www.egappreviews.org/about.htm
[14] National Human Genome Research Institute. Implementing Genomics in Practice (IGNITE) (2016). https://www.genome.gov/27554264/implementing-genomics-in-practice-ignite/
[15] National Human Genome Research Institute. Electronic Medical Records and Genomics (EMERGE)
Network (2016). https://www.genome.gov/27540473/electronic-medical-records-and-genomics- emerge-network/
[16] Institute of Medicine (US). Integrating Large-Scale Genomic Information into Clinical Practice:
Workshop Summary. Washington, DC. National Academies Press (2012). Available from: http://www.ncbi.nlm.nih.gov/books/NBK91500/
[17] Rehm HL, Berg JS, Brooks LD, et al. ClinGen—the clinical genome resource. N Engl J Med. 372(23),
2235-2242 (2015).
[18] Roundtable on Translating Genomic-Based Research for Health; Board on Health Sciences Policy;
Institute of Medicine. Genomics-Enabled Learning Health Care Systems: Gathering and Using Genomic
Science Policy | p. 30
Information to Improve Patient Care and Research: Workshop Summary. Washington, DC. National
Academies Press (2015). Available from: http://www.ncbi.nlm.nih.gov/books/NBK316486/
[19] Horgan D, Jansen M, Leyens L et al. An index of barriers for the implementation of personalized medicine and pharmacogenomics in Europe. Public Health Genomics. 17, 287-298 (2014).
[20] PharmGKB. CPIC: Clinical Pharmacogenetics Implementation Consortium (2016). https://www.pharmgkb.org/page/cpic
[21] PR Newswire. Survey: Most Healthcare Organizations Unprepared for Precision Medicine (2016). http://www.prnewswire.com/news-releases/survey-most-healthcare-organizations-unprepared-for- precision-medicine-300206860.html
[22] HealthData Management. Many Healthcare Organizations Not Preparing for Precision Medicine
(2016). http://www.healthdatamanagement.com/news/many-healthcare-organizations-not-preparing- for-precision-medicine
[23] Horgan D, Jansen M, Leyens L, et al. An index of barriers for the implementation of personalized medicine and pharmacogenomics in Europe. Public Health Genomics, 17, 287-298 (2014).
[24] Duke University School of Medicine. Applied Genomics & Precision Medicine (2014). https://precisionmedicine.duke.edu/policy-resources/educational-resources
[25] Coriell Personalized Medicine Collaborative. Understanding Genetics (2016). https://cpmc.coriell.org/genetic-education/overview
[26] American Nurses Association. Personalized Medicine (2016). http://www.nursingworld.org/genetics
[27] National Human Genome Research Institute. Education (2016). https://www.genome.gov/education/
[28] Mayo Clinic Center for Individualized Medicine. Genomics in Patient Care (2016). http://mayoresearch.mayo.edu/center-for-individualized-medicine/genomics-in-patient-care.asp
Science Policy | p. 31
[29] Personalized Medicine Coalition. Education (2016). http://www.personalizedmedicinecoalition.org/Education/The_Basics
[30] Garrison NA, Sathe NA, Antommaria AHM, et al. A systematic literature review of individuals’ perspectives on broad consent and data sharing in the United States. Genet Med. 18, 663-671 (2016).
[31] Bradbury AR, Patrick-Miller L, Domchek S. Multiplex genetic testing: reconsidering utility and informed consent in the era of next-generation sequencing. Genet Med. 17, 97-98 (2015).
[32] Lorell BH, Mikita JS, Anderson A, Hallinan ZP, Forrest A. Informed consent in clinical research: consensus recommendations for reform identified by an expert interview panel. Clin Trials. 12(6), 692-
695 (2015).
[33] GenomeWeb. NIH Pumps $15M Into Studies on Effects of Genomics Information (2016). https://www.genomeweb.com/research-funding/nih-pumps-15m-studies-effects-genomics- information?utm_source=SilverpopMailing&utm_medium=email&utm_campaign=Daily%20News:%20F oundation%20Medicine%20Sues%20Guardant%20Health%20for%20Patent%20Infringement%20-
%2005/18/2016%2011:00:00%20AM
[34] Inova Translational Medicine Institute. MediMap PGx Testing at Inova (2016). https://www.inova.org/itmi/medimap
[35] BusinessWire. Cigna Builds on Three Years of Success, Expands Genetic Counseling Program (2015). http://www.businesswire.com/news/home/20160421006383/en/Cigna-Builds-Years-Success-Expands-
Genetic-Counseling
[36] Fowler Jr. FJ, Levin CA, Sepucha KR. Informing and involving patients to improve the quality of medical decisions. Health Aff. 30(4), 699-706 (2011).
[37] Novartis Oncology. The Precision Oncology Annual Trend Report: Perspectives From Payers,
Oncologists, and Pathologists (2016).
Science Policy | p. 32
[38] LaRose R, Gregg JL, Strover S, Straubhaar J, Carpenter S. Closing the rural broadband gap: promoting adoption of the internet in rural America. Telecommun Policy. 31, 359-373 (2007).
[39] Sandefer RH, Marc DT, Kleeberg P. Meaningful use attestations among US hospitals: the growing rural-urban divide. Perspect Health Inf Manag. Spring 2015, 1-10 (2015).
[40] Nishi A, Milner DA, Giovannucci EL, et al. Integration of molecular pathology, epidemiology and social science for global precision medicine. Expert Rev Mol Diagn. 16(1), 11-23 (2016).
Science Policy | p. 33
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October 6, 2016 BOARD OF DIRECTORS President Edward Abrahams, Ph.D. Chair ATTN: Robert M. Califf, M.D. William S. Dalton, Ph.D., M.D. U.S. Food and Drug Administration M2Gen Division of Dockets Management Vice Chair Stephen L. Eck, M.D., Ph.D. 5630 Fishers Lane, Room 1061 Astellas Pharma Global Development Rockville, MD 20852 Treasurer D. Stafford O’Kelly Re: Docket Nos. FDA-2016-D-1270 and FDA-2016-D-1233 Altan Pharma, Ltd. Secretary Amy P. Abernethy, M.D., Ph.D. Use of Standards in the Food and Drug Administration’s Regulatory Oversight of Flatiron Health Next Generation Sequencing-Based In Vitro Diagnostics Used for Diagnosing Past President & Chair J. Brian Munroe Germline Diseases: Draft Guidance for Stakeholders and Food and Drug Endo Pharmaceuticals Administration Staff Bonnie J. Addario Bonnie J. Addario Lung Cancer AND Foundation Steven D. Averbuch, M.D. Bristol-Myers Squibb Company Use of Public Human Genetic Variant Databases To Support Clinical Validity for Paul R. Billings, M.D., Ph.D. Next Generation Sequencing-Based In Vitro Diagnostics; Draft Guidance for Biological Dynamics, Inc. Stakeholders and Food and Drug Administration Staff William W. Chin, M.D. PhRMA Dear Dr. Califf: Neil de Crescenzo Change Healthcare
Donna Cryer, J.D. The Personalized Medicine Coalition (PMC) appreciates the opportunity to submit Global Liver Institute comments regarding the U.S. Food and Drug Administration (FDA)’s draft guidance Tim Garnett, FRCOG, MFFP, FFPM documents, Use of Standards in the Food and Drug Administration’s Regulatory Oversight Eli Lilly and Company of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Julie K. Goonewardene Diagnosing Germline Diseases and Use of Public Human Genetic Variant Databases to The University of Texas System Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics. Susan McClure Genome magazine The draft guidance documents raise considerations and policy recommendations for the Howard McLeod, Pharm.D. oversight of certain applications of next generation sequencing (NGS) diagnostic tests. Moffitt Cancer Center Michael Pellini, M.D. PMC, representing innovators, scientists, patients, providers, and payers, promotes the Foundation Medicine understanding and adoption of personalized medicine concepts, services, and products to Kimberly J. Popovits Genomic Health benefit patients and the health system. Hakan Sakul, Ph.D. Pfizer Inc. Jared N. Schwartz, M.D., Ph.D. Personalized medicine is an emerging field that uses diagnostic tools to identify specific Jared N. Schwartz, M.D., Ph.D., LLC biological markers, often genetic, that help determine which medical treatments and Michael Vasconcelles, M.D. procedures will work best for each patient. By combining this information with an Unum Therapeutics Jay G. Wohlgemuth, M.D. individual’s medical records and circumstances, and values, personalized medicine allows Quest doctors and patients to develop targeted prevention and treatment plans.
Our interest in the draft guidance documents pertains to how the concepts therein can support this emerging field. NGS technologies hold great promise for advancing personalized
Science Policy | p. 35 medicine. The ability to know one’s genomic data can and will change the way that physicians and patients evaluate personal health. NGS will allow for the identification of many genetic variants at once. This information can be used to make health care decisions based on the genetic makeup of each individual patient, thus truly personalizing health care.
While NGS holds great promise for the future of health care, appropriate regulatory oversight of these innovations will be needed to protect patients while maintaining a strong environment for innovation. Providing optimal access to high-quality validated diagnostic tests will help deliver on the promise of personalized medicine while protecting patients and public health.
Scope and Statement of Neutrality
PMC is focusing these comments on the use of standards for the oversight of NGS-based IVDs and the use of public human genetic variant databases as they relate to personalized medicine diagnostic tests. These comments do not pertain to the use of NGS technologies for ancestry testing and other direct-to consumer, non-medical applications.
Many of PMC’s members will present their own responses to the agency and will actively advocate for those positions. PMC’s comments are designed to provide feedback so that the general concept of personalized medicine can advance, and are not intended to impact adversely the ability of individual PMC members, alone or in combination, to pursue separate comments with respect to the guidance documents or related issues. PMC’s response is focused exclusively on personalized medicine issues related to all genomic diagnostic tests, including NGS and all accompanying technologies (the combination of these is referred to herein as NGS).
Since our comments are focused on how NGS technologies can advance personalized medicine, and because there are some differences of opinion within our membership, PMC will not take a position on whether FDA has the statutory authority to regulate laboratory developed tests (LDTs) as medical devices or on the processes by which FDA may regulate them, even though many NGS-based diagnostic tests are developed and performed in single laboratory enterprises.
Acknowledgement of FDA’s Efforts on Genomic Technologies
These draft guidance documents represent new concepts and processes for the regulation of diagnostic tests with consideration of the impracticality of applying some traditional processes to NGS tests. They demonstrate FDA’s creativity and progressive approach to policy development.
PMC appreciates that FDA is engaging diverse stakeholders at the earliest stages of development in order to promote thought and incorporate various perspectives. We encourage FDA to continue that engagement, and look forward to working with the agency on this topic.
2 Science Policy | p. 36
Modifications to Existing Tests
While an NGS test itself might not functionally change, the clinical application of the information provided by the test may change over time with additional knowledge about genomic variants and their clinical significance. While we cannot assume that the detection of additional mutations provides new or improved clinically actionable information, FDA should be willing to accept a reasonable level of evidence to analytically validate additional or expanded endpoints.
Requiring revalidation of tests end-to-end for each additional modification, including aggregate validation of previous modifications, is impractical for many NGS-based diagnostic tests, and could have a significant chilling effect on innovation. The agency should devise new processes for reporting and validating modifications that do not impair performance of existing NGS-based tests.
Recommendations and Requests for Clarification Regarding Use of Standards in FDA Regulatory Oversight of NGS-Based IVDs (Docket No. FDA-2016-D-1270)
Many of the issues described within the draft guidance document titled Use of Standards in the Food and Drug Administration’s Regulatory Oversight of Next Generation Sequencing-Based In Vitro Diagnostics Used for Diagnosing Germline Diseases are best evaluated by experts within the clinical genetics and laboratory testing fields. However, we offer these comments about the scope of the draft guidance and how it could affect the field of personalized medicine in general.
Limitations
The draft guidance document provides “non-binding” recommendations for the use of standards and databases for FDA oversight of NGS-based IVDs. The document describes, however, a class II, de novo process for classification of germline tests, thereby potentially providing a less onerous pathway regarding pre-market requirements. Additional clarification is needed regarding the FDA’s decision requirements for de novo requests for NGS tests, and the binding versus non-binding implications of the subsequent classification.
PMC appreciates that this first foray into a new process for regulatory oversight addresses only one discrete subcategory of uses for NGS-based testing, but we note that the majority of uses for NGS tests are thereby not covered. Uses that are not addressed include screening, microbial genome testing, risk prediction, tumor genome sequencing, and use as companion diagnostics. The processes developed here should be considered when developing policies for regulatory oversight of these other applications and contexts, and if possible, the FDA should develop, and share with the public, a timeline for expanding these policies to other uses of NGS-based tests.
3 Science Policy | p. 37 Analytical Validity Determination
FDA’s oversight of NGS must facilitate safe, accurate, and reliable determination of clinically relevant information without being overly burdensome. Policies and processes for the regulatory oversight of NGS-based tests should provide access to novel technologies and promote innovation.
In this context, the analytical validity determination recommendations outlined in the draft guidance may in some ways be too specific for this stage of policy development. The specificity of the document is particularly notable when one considers its application for technological areas in which there is not yet a clear path for the use of standards. The FDA should remain flexible in consideration of revising initial benchmarks and policies as NGS technologies continue to develop. We suggest that FDA develop a process for regular review of relevant policies as well as validity assertions of database endpoints. The agency should establish processes in coordination with database administrators and test developers and allow for necessary adjustments that assure safety, accuracy, and appropriate access to novel tests.
Performance Characteristics
The standards for accuracy described in the draft guidance document are, in many cases, difficult to achieve, and may be overly stringent.
NGS performance characteristics are often dependent on a test’s intended use and the characteristics of the applicable population. The agency should adjust performance thresholds to take into account the genes being interrogated, risks to the tested population of false-negative or false-positive results, and potential uses of information. Minimum performance thresholds may not be necessary in all contexts. The guidance document acknowledges this in section VI-A-5: “Performance Needs,” which states that performance thresholds should consider metrics based on a test’s indication and predefined user needs.
Performance characteristic expectations can vary widely depending on the target enrichment platform, the genome region of interest, and the type of variant being interrogated. The suggested thresholds for positive and negative percent agreement (PPA and NPA), technical positive predictive value (TPPV), and some test run quality metrics are high and may not be attainable for certain variant types including but not limited to whole genome sequencing, some difficult to sequence regions of the genome, and heterozygous variants. Thus, the agency should not apply a single performance threshold metric to all variants. The agency should instead calibrate the threshold levels and metrics when possible, based on variant type, genome region, and target enrichment, as well as the intended use of the NGS based test.
Consideration of Existing Standards
While establishing analytic validation characteristics for germline NGS-based tests, FDA should take into consideration established guidelines for germline and related diagnostic tests that have been developed by professional organizations including the American College of Medical Genetics (ACMG), the New York State Department of Health (NYSDH), and the College of American Pathologists (CAP). While these guidelines may
4 Science Policy | p. 38 not apply strictly to NGS-based platforms, many of the concepts within may be applicable across testing platforms and intended uses.
Recommendations and Requests for Clarification Regarding Use of Public Human Genetic Variant Databases to Support Clinical Validity for NGS-Based IVDs (Docket No. FDA-2016-D-1233)
We commend FDA for developing policies applicable to the use of publicly accessible databases of genetic variants to establish clinical validity for NGS-based diagnostic tests. We offer these comments pertaining to how it could affect the field of personalized medicine in general.
Regulatory Grade
It is unclear what constitutes “regulatory grade” with respect to public databases. Further clarity is needed on what parameters (evidentiary classifications, adherence to defined standards, curation methods, accessibility requirements, etc.) are considered to classify a database as regulatory grade.
Differentiating Responsibilities
The responsibilities of FDA, database administrators, and test data submitters are not clearly delineated, especially as they pertain to curation, variant interpretation, and tracking. Further clarification is necessary regarding who is responsible for specific elements and processes for achieving regulatory grade compliance, and who is responsible for tracking approved submissions in the database to make sure that they accurately depict known versus unknown clinical significance, as this may change over time, and otherwise keep up with the state of the science.
The agency has stipulated that variant calls require a minimum of two experts to agree. While that standard may be largely acceptable, in the case of rare variants, it may not always be feasible. We suggest that the agency consider recognized professional guidelines, such as the National Comprehensive Cancer Network (NCCN) guidelines, and recently established and curated databases, such as the Genomic Data Commons (GDC), to keep pace with current research and to potentially limit time and resource constraints. The recognition of guidelines and quality databases may ensure an efficient process that expedites access to meaningful information that can inform care.
Accessibility
PMC supports process-driven transparency and public accessibility of variant databases. The agency should consider, however, limiting the ability to report emerging information when defining accessibility requirements.
Where possible, there should be an effort to incorporate real-time observational data obtained through learning health systems with appropriate classification of the quality of information such as investigational use only, disputed significance, and other data quality indicators. How often a database incorporates new data will be important for reporting variant interpretations.
Conclusions/Recommendations
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PMC recognizes and appreciates that the processes described in the draft guidance documents could represent a paradigm shift in how diagnostic tests are conducted, interpreted, and regulated.
Some elements of the innovative approaches to the regulatory oversight of NGS-based tests that the FDA has described in these draft guidance documents have many elements that could be applied to other diagnostic platforms and technologies in personalized medicine. We recommend that FDA consider applying these oversight elements to other diagnostic technologies regulated under the FFDCA, such as Sanger sequencing, mass spectrometry-based tests, multiplex genetic panels, and other PCR-based assays, as appropriate.
As the agency continues to consider these concepts, there are four key overarching principles that should be recognized: 1. Information from NGS-based diagnostic tests must be validated, accurate, and reliable. 2. Patients should be assured access to state-of-the art technologies. 3. Oversight policies must provide a process for easily reporting and validating modifications of NGS-based tests. 4. FDA must continue to engage all stakeholders to develop important details on how such an oversight system would be resourced, standardized, and administered.
PMC appreciates the opportunity to provide these comments. PMC and FDA are united by a shared goal to provide patients and health care providers with safe and effective technologies that will best serve the needs of patients and the health care system. If you have any questions about the content of this letter, please contact me at [email protected] or (202) 787-5912. We look forward to further opportunities to provide feedback.
Sincerely yours,
Daryl Pritchard, Ph.D. Vice President, Science Policy
6 Science Policy | p. 40
POLICY COMMITTEE MEETING AGENDA
Tuesday, June 21, 2016, 12:00 - 2:00 p.m. ET Concourse Large Room (C-115) Center for Strategic & International Studies (CSIS) building 1616 Rhode Island Ave. NW Washington, D.C. 20036
12:00 p.m. ET – Welcome: Daryl Pritchard, Ph.D. PMC Vice President, Science Policy
12:00 p.m. ET – Envisioning Value in An Overview of the Value Assessment Process Personalized Medicine: Dan Leonard President NPC
The ICER Value Framework Rick Chapman, Ph.D. Director, Health Economics ICER
Stakeholder Response Randy Burkholder Vice President, Policy and Research PhRMA
Donna R. Cryer, J.D. President & CEO Global Liver Institute
Audience Q & A
1:00 p.m. ET – Business Meeting: Public Policy Amy M. Miller, Ph.D. • ICER value assessment framework PMC Executive Vice President • CMS' initial 2017 gapfill payment rates
Daryl Pritchard, Ph.D. Science Policy PMC Vice President, Science Policy • FDA's draft guidance on preparation of genomic samples • Update on clinical integration of personalized medicine initiative • The Personalized Medicine Report
Chris Wells Online Education Initiative PMC Director of Communications • Progress to date • Ongoing opportunities
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POLICY COMMITTEE MEETING AGENDA
Tuesday, October 11, 2016, 12:00 - 2:00 p.m. ET Concourse Large Room (C-115) Center for Strategic & International Studies (CSIS) building 1616 Rhode Island Ave. NW Washington, D.C. 20036
12:00 p.m. ET Welcome
Daryl Pritchard, Ph.D. Introduction PMC Vice President, Science Policy
Stephanie Devaney, Ph.D. The Map to a Million: An Update on the Project Manager, Precision Medicine Initiative Precision Medicine Initiative Office of the Chief of Staff The White House
1:00 p.m. ET Business Meeting:
Daryl Pritchard, Ph.D. Next-Generation Sequencing Draft Guidance PMC Vice President, Science Policy • Use of Standards in FDA Regulatory Oversight of Next-Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases (July 8, 2016)
• Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next-Generation Sequencing (NGS)-Based In Vitro Diagnostics (July 8, 2016)
• PMC's response (October 6, 2016)
Amy M. Miller, Ph.D. Codevelopment Draft Guidance PMC Executive Vice President • Principles for Codevelopment of an In Vitro Companion Diagnostic Device With a Therapeutic Product (July 15, 2016)
• PMC's response
continued on back
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Amy M. Miller, Ph.D. The Institute for Clinical and PMC Executive Vice President Economic Review (ICER)
• ICER on Non-Small Cell Lung Cancer o Draft scoping document (June 21, 2016) o PMC's comment letter (June 28, 2016) o Draft evidence report
• ICER's National Call for Proposed Improvements to Value Assessment Framework (July 14, 2016) o PMC’s comment letter (September 12, 2016)
PMC's White Paper on Value Assessment
New Business
Chris Wells Announcements PMC Director, Communications • 12th Annual Personalized Medicine Conference at Harvard Medical School, November 15 – 17, Boston, MA
• Policy Committee Meeting with Joe V. Selby, M.D., M.P.H., Executive Director, Patient- Centered Outcomes Research Institute (PCORI), December 7, 3:00 p.m., CSIS building, Washington, DC
• Holiday Party, December 7, 5:00 p.m., Tabard Inn, Washington, DC
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POLICY COMMITTEE MEETING AGENDA
Wednesday, December 7, 2016, 3:00 - 5:00 p.m. ET Concourse Large Room (C-115) Center for Strategic & International Studies (CSIS) building 1616 Rhode Island Ave. NW Washington, D.C. 20036
3:00 p.m. ET Welcome & Introduction Edward Abrahams, Ph.D. PMC President • Personalized medicine in 2017 • PMC’s 2017 Strategic Plan
Updates • 12th Annual Personalized Medicine Conference recap • Update on "The Clinical and Economic Value of Next-Generation Sequencing: A Research Project" • Update on PMC's Education Initiative • Advancing Access to Personalized Medicine: A Comparative Assessment of International Regulatory, Reimbursement and Health Technology Systems • PMC's forthcoming white paper on value assessment • "Evidence for Coverage and Payment of Personalized Medicine Diagnostics" • Update on The Personalized Medicine Report
2017 Planning • PMC priorities • Policy meeting speakers
3:45 p.m. ET PCORI's Personalized Medicine Agenda in 2017 Joe V. Selby, M.D., M.P.H. Executive Director Patient-Centered Outcomes Research Institute (PCORI)
4:10 p.m. ET FDA's Personalized Medicine Agenda in 2017 Elizabeth Mansfield, Ph.D. Deputy Office Director, Personalized Medicine and Molecular Genetics, Office of In Vitro Diagnostics and Radiological Health, CDRH FDA
5:00 p.m. ET PMC Holiday Party Tabard Inn 1739 N Street NW Washington, DC 20036
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Science Policy | p. 48 An Infrastructure for Innovation: How the 21st Century Cures Bill Could Establish a More Favorable Landscape for Personalized Medicine in 2017
December 6, 2016 by Daryl Pritchard, Ph.D., PMC Vice President, Science Policy
Barack Obama’s administration was clearly committed to the advancement of personalized medicine. In addition to launching the All of Us Research Program (formerly called the Precision Medicine Initiative) and the Cancer Moonshot effort, during his tenure President Obama regularly described personalized medicine as the future of health care.
“I want the country that eliminated polio and mapped the human genome to lead a new era of medicine, one that delivers the right treatment at the right time,” he said in his 2015 State of the Union Address.
The election of Donald Trump as the 45th President has led to a great deal of uncertainty on the future of personalized medicine and the fate of Obama’s signature personalized medicine programs.
Fortunately, Congress has confirmed its support for personalized medicine by championing the 21st Century Cures bill, which the House of Representatives passed last week by a 392 – 26 vote. The bill, designed to accelerate the pace of biomedical innovation, a goal that President-elect Trump has expressed interest in, would provide continued momentum for personalized medicine.
Science Policy | p. 49 “The 21st Century Cures bill supports personalized medicine,” PMC President Edward Abrahams said. “The Precision Medicine Initiative, the Cancer Moonshot and speedier access to innovative therapies based on molecular pathways, in particular, will all contribute to a healthier nation.”
Among other things, the bill:
• Authorizes $4.8 billion in funding over 10 years for programs at the National Institutes of Health (NIH) that include the All of Us Research Program and the Cancer Moonshot Research Program, as well as $500 million for FDA to implement provisions to improve innovation
• Requires FDA to make the patient experience a more central part of the drug development process
• Establishes a review pathway at FDA for biomarkers and other drug development tools
• Includes provisions related to FDA’s oversight of diagnostics, albeit without addressing the longstanding debate on the regulation of laboratory-developed tests
• Modernizes clinical trial design and evidence development as it relates to the consideration of real-world data and other topics
• Requires FDA to pilot one or more inter-center institute(s) to help develop and implement processes for coordination of activities in major disease areas between the drug, biologics and device centers
• And enhances the country’s capacity to deliver personalized medicine through improvements and incentives in health information technology.
The bill is not perfect. Policymakers have pointed out, for example, that the amount of NIH funding is half of what was proposed in the 2015 version, and that the programs are authorized rather than appropriated, thereby not guaranteeing that they will be funded. Others object to using the Affordable Care Act’s prevention funds to pay for Cures provisions. Furthermore, although proponents claim the bill’s new measures will not weaken FDA’s regulatory oversight, some critics disagree, especially regarding regenerative medicine.
But despite these concerns, the 21st Century Cures Act provides a more favorable setting for personalized medicine amid ongoing uncertainty under a new administration.
The Senate plans to consider the bill tomorrow.
The Personalized Medicine Coalition calls on Congress to pass the legislation and deliver it to the President, who has indicated his strong support for its provisions. By allocating resources for personalized medicine programs and encouraging biomedical innovation, a 21st Century Cures law could drive personalized medicine’s enormous potential for patients and the health system in a future that otherwise remains uncertain.
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The Personalized Medicine Report
The Personalized Medicine Coalition 2017
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TABLE OF CONTENTS
Introduction ……………………………………………………………………………………… p. x Why It Matters: The Benefits of Personalized Medicine …………………………………………………. p. x Sustaining Progress …………………………………………………………………………………………………….. p. xx Scientific Advancement ………………………………………………………………………. p. xx Genomic Sequencing …………………………………………………………………………………………………….. p. xx Human Biology and Disease Susceptibility: The Role of Genetics, Epigenetics and Proteins .. p. xx Immunotherapy …………………………………………………………………………………………………………….. p. xx CRISPR/Cas9 Gene Editing …………………………………………………………………………………………….. p. xx Regulatory Policy ………………………………………………………………………………… p. xx Personalized Medicine Tests …………………………………………………………………………………………. p. xx Regulatory Oversight of NGS-Based Diagnostic Tests …………………………………………………….. p. xx Codevelopment ……………………………………………………………………………………………………………. p. xx Coverage and Payment Policy ……………………………………………………………… p. xx Personalized Medicine Value Proposition ……………………………………………………………………… p. xx Value Assessment Frameworks ……………………………………………………………………………………. p. xx The Reimbursement Landscape ……………………………………………………………………………………. p. xx Payment and Delivery System Reform ………………………………………………………………………….. p. xx Clinical Adoption ………………………………………………………………………………… p. xx Education and Awareness …………………………………………………………………………………………….. p. xx Patient Empowerment …………………………………………………………………………………………………. p. xx Value Recognition ………………………………………………………………………………………………………… p. xx Infrastructure and Information Management ………………………………………………………………… p. xx Ensuring Access to Care ………………………………………………………………………………………………… p. xx Health Information Technology …………………………………………………………… p. xx Government Support …………………………………………………………………………………………………….. p. xx Electronic Health Records ……………………………………………………………………………………………… p. xx Mobile Technologies ……………………………………………………………………………………………………… p. xx A ‘Learning Health Care System’ …………………………………………………………………………………….. p. xx Conclusion ………………………………………………………………………………………….. p. xx
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INTRODUCTION
When it comes to medicine, one size does not fit all. Traditionally, health care practice would involve consideration of a patient’s symptoms, diagnosis of a health condition, and administration of a standard treatment. Providers would only consider alternative treatments when the standard treatment did not lead to an improved condition. For many patients, however, standard treatments may be ineffective (Figure 1), and in some cases, they may even cause severe adverse side effects.
Enter personalized medicine. Personalized medicine, also called precision or individualized medicine, is an evolving field in which physicians use diagnostic tests to identify specific biological markers, often genetic, that help determine which medical treatments and procedures will work best for each patient. By Historical Precedent combining this information with an For more than two millennia, medicine has not wavered from its aspiration of being individual’s medical records and personalized. In ancient times, Hippocrates circumstances, personalized medicine combined an assessment of the four humors—blood, phlegm, yellow bile, and allows doctors and patients to black bile—to determine the best course of develop targeted treatment and treatment for each patient. Today, the sequence of the four chemical building blocks prevention plans. that comprise DNA, coupled with telltale proteins in the blood, enable more accurate Health care is in the midst of a medical predictions. transformation away from one-size- fits-all, trial-and-error medicine and toward this new, targeted approach that utilizes patients’ molecular information to inform treatments. Personalized health care has the capacity to detect the onset of disease at its earliest stages, pre-empt the progression of disease, and, at the same time, increase the efficiency of the health care system by improving quality, accessibility, and affordability.
Personalized medicine is especially established in oncology. Some clinical centers now routinely offer patients with melanoma, leukemia, or metastatic lung, breast, or brain cancers a “molecular diagnosis.” These diagnoses allow physicians to select
Science Policy | p. 53 The Case for Personalized Medicine 1
FIGURE 1: ONE SIZE DOES NOT FIT ALL Percentage of the patient population for which a particular drug in a class is ineffective, on average.
ANTI-DEPRESSANTS 38% SSRIs
ASTHMA DRUGS 40%
DIABETES DRUGS 43%
ARTHRITIS DRUGS 50%
ALZHEIMER’S DRUGS 70%
CANCER DRUGS 75%
Patients respond differently to the same medicine.
Reproduced with permission from: Spear, BB, Heath-Chiozzi, M, Huff, J. Clinical application of pharmacogenetics. Trends in Molecular Medicine. 2001;7(5): 201-204.
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tailored treatments that can greatly “Personalized medicine is our chance to improve the chances of survival. revolutionize health care, but it will require a team effort by innovators, Many cancers can now be sub- entrepreneurs, regulators, payers and classified by genetics (e.g., BRAF- policymakers.” positive melanoma). Treatments - Brook Byers, Partner, Kleiner Perkins targeting genetic variants involved in Caufield & Byers the molecular pathway of disease, such as BRAF in melanoma and ALK in non-small cell lung cancer, represent a remarkable improvement over trial-and-error medicine, and we are not far from an era in which we treat most cancer cases with a targeted course of treatment (Figure 2).1
We have also made great strides in pharmacogenomics. Pharmacogenomic tests help predict what medications at what doses will be safest and most effective for individuals based on their genetic makeup. The genotyping of drug-metabolizing enzymes has improved dosing of drugs for conditions as wide-ranging as depression and anxiety, coronary and peripheral artery disease, inflammatory bowel disease, and cancer. This has enabled patients to avoid harmful side effects, adverse drug interactions, or ineffective treatments, and helped them get on effective intervention regimens faster.
Why It Matters: The Benefits of Personalized Medicine
These developments have a lot to offer both patients and the health care system. Personalized medicine can, for example:
• Shift the emphasis in medicine from reaction to prevention • Direct targeted therapy and reduce trial-and-error prescribing • Reduce adverse drug reactions • Reveal stratified or expanded uses for medicines and drug candidates
1 Winslow, R. Major shift in war on cancer. Wall Street Journal. June 5, 2011. Accessed September 13, 2016 at http://www.wsj.com/articles/SB10001424052702304432304576367802580935000.
Science Policy | p. 55 2 Introduction
FIGURE 2: FORGING A PATH TO PERSONALIZED CANCER CARE TACKLING TUMORS: Percentage of patients whose tumors were driven by certain genetic mutations that could be targets for specific drugs, by types of cancer.
Melanoma 73% Thyroid 56% Colorectal 51% Endometrial 43% Lung 41% Pancreatic 41% Breast 32% Other gynecological 31% Genitourinary 29% Other gastrointestinal 25% Ovarian 21% Head and neck 21%
Reproduced with permission from: Winslow, R. Major shift in war on cancer. Wall Street Journal. June 5, 2011. Accessed September 13, 2016, at http://www.wsj.com/articles/SB1000142405270230 4432304576367802580935000.
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• Increase patient adherence to treatment • Reduce high-risk invasive testing procedures • Help control the overall cost of health care
Shifting the Emphasis in Medicine from Reaction to Prevention
Personalized medicine introduces the ability to uncover molecular markers that signal disease risk or presence before clinical signs and symptoms appear, offering an opportunity to focus on prevention and early intervention rather than on reaction at advanced stages of disease.
In some areas, early genetic testing can save lives. For example, women with certain BRCA1 or BRCA2 gene variations have up to an 85 percent lifetime chance of developing breast cancer, compared to a 13 percent chance among the general female population.2 3 4 Women with harmful BRCA1 and BRCA2 mutations also have up to a 39 and 17 percent chance, respectively, of developing ovarian cancer, compared with a 1.3 percent chance among the general female population.2 The BRCA1 and BRCA2 genetic test can guide preventive measures, such as prophylactic surgery, chemoprevention and more frequent mammography.
Directing Targeted Therapy and Reducing Trial-and-Error Prescribing
With a personalized approach, doctors can sometimes identify the most effective treatment for a patient immediately by testing for specific molecular characteristics, thus avoiding the frustrating and costly practice of trial-and-error medicine. Medicines that target those molecular characteristics often improve outcomes. One of the most common applications of this practice has been for women with breast
2 National Cancer Institute. BRCA1 and BRCA2: Cancer Risk and Genetic Testing. Accessed September 13, 2016 at http://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet. 3 Struewing, JP, Hartge, P, Wacholder, S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. The New England Journal of Medicine. 1997;336(20): 1401-8. 4 National Cancer Institute. SEER Cancer Statistics Review, 1975-2003. Accessed September 13, 2016 at http://seer.cancer.gov/archive/csr/1975_2003/.
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cancer. About 30 percent of breast cancer cases are characterized by over- expression of a cell-surface protein called human epidermal growth factor receptor 2 (HER2). For breast cancer patients who express this molecule, adding an antibody drug like trastuzumab (Herceptin®) to their chemotherapy regimen can reduce the recurrence of a tumor by 52 percent.5 6 Molecular diagnostic tests for HER2 are used to identify the patients who will benefit from receiving Herceptin® and other drugs that target HER2, such as lapatinib (Tykerb®).
Some diagnostic tests measure “The power in tailored therapeutics is for prognostic markers that help us to say more clearly to payers, providers and patients — ‘this drug is not for indicate how a disease may develop everyone, but it is for you.’ That is in an individual when a disorder is exceedingly powerful.” already diagnosed. Two complex - John C. Lechleiter, Ph.D., Chairman, diagnostic tests, Oncotype DX® and President and CEO, Eli Lilly and Company MammaPrint®, for example, use prognostic markers to help physicians target the best course of treatment for breast cancer patients. Oncotype DX® can determine whether women with certain types of breast cancer are likely to benefit from chemotherapy.7 8 9 MammaPrint® can detect which early-stage breast cancer patients are at risk of distant recurrence following surgery.10 Both tests place patients into risk categories that inform physicians and
5 Piccart-Gebhart, MJ, Procter, M, Leyland-Jones, B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. The New England Journal of Medicine. 2005;353: 1659-1672. 6 Romond, EH, Perez, EA, Bryant, J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. The New England Journal of Medicine. 2005;353: 1673-1684. 7 Hornberger, J, Cosler, LE, Lyman, GH. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer. American Journal of Managed Care. 2005;11: 313-324. 8 Paik, S, Tang, G, Shak, S, et al. Gene expression and benefit of chemotherapy in women with node- negative, estrogen receptor–positive breast cancer. Journal of Clinical Oncology. 2006;24: 3726-3734. 9 Cronin, M, Pho, M, Dutta, D, et al. Measurement of gene expression in archival paraffin-embedded tissues. The American Journal of Pathology. 2004;164(1): 35-42. 10 Agendia NV. MammaPrint® 70-Gene Breast Cancer Recurrence Assay. Accessed September 13, 2016 at http://www.agendia.com/healthcare-professionals/breast-cancer/mammaprint/.
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patients of whether the cancer may be treated successfully with hormone therapy alone, as opposed to some combination of hormone therapy and chemotherapy, which is associated with an additional financial burden and toxic effects. Similar prognostic tests for prostate and colon cancer patients have also been developed.11 12 13
Reducing Adverse Drug Reactions
As indicated above, pharmacogenomic tests help predict what medications at what doses will be safest for individuals based on their genetic makeup. Doing so is important. According to several studies, about 5.3 percent of all hospital admissions are associated with adverse drug reactions (ADRs).14 Many ADRs are attributed to variations in genes that code for drug-metabolizing enzymes, such as cytochrome P450 (CYP450).15 16 These variants cause drugs to be metabolized either faster or slower than normal. As a result, some individuals have trouble inactivating a drug and eliminating it from their bodies, leading to “overdose toxicity,” while others eliminate the drug too rapidly before it has had a chance to work. Thus, these genetic variations should be considered when determining dose.
11 Myriad. Prolaris® Test Predicts Mortality Risk in Prostate Cancer Biopsy Study. Accessed September 13, 2016 at http://investor.myriad.com/releasedetail.cfm?releaseid=848939. 12 Agendia NV. Coloprint® 18-Gene Colon Cancer Recurrence Assay. Accessed September 13, 2016 at http://www.agendia.com/healthcare-professionals/colon-cancer/. 13 Genomic Health. Oncotype Dx (For Colon Cancer). Accessed December 2, 2016 at http://www.oncotypedx.com/.
14 Kongkaew, C, Noyce, PR, Ashcroft, DM. Hospital admissions associated with adverse drug reactions: A systematic review of prospective observational studies. Annals of Pharmacotherapy. 2008;42(7): 1017-1025. 15 Phillips, KA, Veenstra, DL, Oren, E, et al. Potential role of pharmacogenomics in reducing adverse drug reactions: A systematic review. Journal of the American Medical Association. 2001;286: 2270- 2279. 16 Blue Cross Blue Shield Technology Evaluation Center. Special Report: Genotyping for cytochrome P450 polymorphisms to determine drug-metabolizer status. Technology Evaluation Center Assessment Program. 2004;19(9): 1-2.
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Pharmacogenomic testing can help guide the safe application of medicines in many health areas, including heart disease, hematologic disorders, HIV and other infectious diseases, cancer adjunct therapy, anesthesiology, dermatology, gastroenterology, neurology, psychiatry, and rheumatology. One of the first applications of pharmacogenomics was for patients that had been prescribed the drug warfarin, used to prevent blood clots. The safe use of warfarin is complicated by genetic variations in a drug-metabolizing enzyme (CYP2C9) and an enzyme that activates vitamin K (VKORC1). 17 18 Dosing is typically adjusted for the individual patient through multiple rounds of trial-and-error, during which the patient may be at risk for excessive bleeding or further blood clots. FDA now recommends genotyping for all patients before warfarin treatment, which allows for more precise dosing. Although the data are still evolving, early evidence suggests that genetic testing in advance of prescribing warfarin helps patients avoid serious and possibly fatal adverse effects.19 20
The use of genetic markers to facilitate safer and more effective drug dosing and selection takes on added significance at the population level. For example, adverse reactions to the HIV drugs efavirenz (Stocrin®/Sustiva®) can occur at standard dosing due to the presence of the CYP2B6*6 allele. This results in slower metabolism of the drug and is found significantly more often in African heritage- than in European heritage-based populations.21 Lowering the drug dose in
17 Mangravite, LM, Thorn, CF, Krauss, RM. Clinical implications of pharmacogenomics of statin treatment. The Pharmacogenomics Journal. 2006;6(6): 360-374. 18 Rieder, MJ, Reiner, AP, Gage, BF, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. The New England Journal of Medicine. 2005;352: 2285-2293. 19 U.S. Food and Drug Administration. FDA Approves Updated Warfarin (Coumadin®) Prescribing Information. Accessed September 13, 2016 at http://www.fda.gov/newsevents/newsroom/pressannouncements/2007/ucm108967.htm. 20 Kimmel, SE, French, B, Kasner, SE, et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing. The New England Journal of Medicine. 2013;369: 2283-2293. 21 Nyakutira, C, Roshammar, D, Chiqutsa, E, et al. High prevalence of the CYP2B6 516G->T(*6) variant and effect on the population pharmacokinetics of efavirenz HIV/AIDS outpatients in Zimbabwe. European Journal of Clinical Pharmacology. 2008;64(4): 357-365.
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individuals with this allele can help reduce adverse effects and increase treatment compliance.
Revealing Stratified or Expanded Uses for Medicines and Drug Candidates
Molecular testing can also help “Within the last decade, [scientific advancements] have enabled us to move from identify the most appropriate classifying the disease by what can be seen uses for therapies that were under a microscope, to looking at the patient’s molecular profile.” initially targeted to the general
- Gideon M. Blumenthal, M.D., Clinical Team population. The lung cancer Leader, Lung Cancer and Head and Neck drug gefitinib (Iressa®), for Cancer, Scientific Liaison, Lung Cancer, Center for Drug Evaluation and Research, FDA example, did not demonstrate a survival advantage in a general - Richard Pazdur, M.D., Acting Director, Oncology Center for Excellence, FDA population of lung cancer patients in clinical trials, and was withdrawn from the market in 2005 after initially being granted accelerated approval in 2003. However, after continued clinical development using molecular testing to demonstrate benefit in about 10 percent of patients who test positive for epidermal growth factor mutations, FDA approved Iressa® as a first line treatment for this subset of NSCLC patients in 2015.
Genomic analysis has led to an evolution in the way tumors are classified. With an increasing body of knowledge about the underlying genomic alterations, tumor classification is shifting away from tissue of origin and toward molecular taxonomy, which is having a profound effect on the way that oncology treatment decisions are made. For example, trial results suggest that expression of the PD-L1 biomarker, which has been widely observed in cancers from multiple tissues of origin, is the key factor to predicting efficacy of novel immune checkpoint inhibitors like
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pembrolizumab (Keytruda®) and nivolumab (Opdivo®), and FDA has approved their use for multiple indications.22 23 24 25 26
Likewise, early studies indicate that crizotinib (Xalkori®), targeting EML4-ALK– positive, non–small cell lung cancers, is effective against other types of tumors containing ALK alterations, such as aggressive forms of pediatric neuroblastoma and anaplastic large cell lymphoma.27 28 FDA has fast-tracked regulatory review for these expanded indications.
Increasing Patient Adherence to Treatment
Patient non-compliance with treatment leads to adverse health effects and increased overall health care costs. When personalized therapies prove more effective or present fewer side effects, patients may be more likely to comply with
22 U.S. Food and Drug Administration. FDA Approves Keytruda for Advanced Melanoma. Accessed November 2, 2016 at http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm412802.htm. 23 Festino, L, Botti, G, Lorigan, P, et al. Cancer treatment with anti-PD-1/PD-L1 agents: Is PD-L1 expression a biomarker for patient selection? Drugs. 2016;76(9): 925-945. 24 U.S. Food and Drug Administration. FDA Approves Keytruda for Advanced Non-Small Cell Lung Cancer. Accessed November 2, 2016 at http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm465444.htm. 25 BioSpace. FDA bestows Merck & Co. (MRK)’s Keytruda with breakthrough status to treat advanced colorectal cancer. BioSpace. November 2, 2015. Accessed November 2, 2016 at http://www.biospace.com/News/fda-bestows-merck-co-s-keytruda-with-breakthrough/397267. 26 Pollack, A. Immunotherapy drug Opdivo fails clinical trial to expand use. The New York Times. August 5, 2016. Accessed November 2, 2016 at http://www.nytimes.com/2016/08/06/business/lung-cancer-drug-opdivo-fails-clinical-trial-to- expand-use.html. 27 Mosse, YP, Balis, FM, Lim, MS, et al. Efficacy of crizotinib in children with relapsed/ refractory ALK- driven tumors including anaplastic large cell lymphoma and neuroblastoma: A Children’s Oncology Group phase I consortium study. Journal of Clinical Oncology. 2012;30 (suppl; abstr. 9500). 28 Camidge, DR, Bang, YJ, Kwak, EL, et al. Activity and safety of crizotinib in patients with ALK- positive non-small-cell lung cancer: Updated results from a phase 1 study. The Lancet Oncology. 2012;13(10): 1011-1019.
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their treatments. The greatest impact could be in the treatment of chronic diseases, for which non-compliance commonly exacerbates the condition.
For example, inherited forms of hypercholesterolemia (high cholesterol) can increase the risk of myocardial infarction before the age of 40 by more than 50-fold in men and 125-fold in women. Knowledge of a genetic predisposition for hypercholesterolemia provides patients with a powerful incentive to make lifestyle changes and manage their condition with drugs. Patients with a genetic diagnosis have shown more than 86 percent adherence to their treatment program after two years, compared to 38 percent prior to testing.29
Avoiding Invasive Testing Procedures
Molecular diagnostic tests that simply require a blood sample can also sometimes replace invasive and uncomfortable tissue biopsies. For example, Allomap®, a multi-gene expression test, detects whether the immune system of heart transplant recipients is rejecting the new organ. 30 Approximately 25 percent of heart transplant patients experience a rejection, which can prove fatal. To monitor for rejection, endomyocardial biopsies are performed as frequently as once a week after the transplant, and then every few months thereafter for several years. This invasive procedure requires inserting a tube into a vein in the neck and threading it to the heart to obtain the biopsy, which is uncomfortable for patients and has risks associated with injury to the vein and heart. Patients who are monitored for rejection using Allomap® have equivalent outcomes as those who receive endomyocardial biopsies, but without the associated risks and complications.31 32
29 Umans-Eckenhausen, MA, Defesche, JC, van Dam, MJ, et al. Long-term compliance with lipid- lowering medication after genetic screening for familial hypercholesterolemia. Archives of Internal Medicine. 2003;163(1): 658. 30 CareDx. Personalizing Care for Heart Transplant Patients. Accessed September 13, 2016 at http://www.allomap.com/.
31 Pham, MX, Teuteberg, JJ, Kfoury, AG, et al. Gene-expression profiling for rejection surveillance after cardiac transplantation. The New England Journal of Medicine. 2010;362: 1890-1900.
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Helping to Control the Overall Cost of Health Care
Personalized medicine also has the potential to reduce health care costs worldwide, where in many countries the cost of health care is on an unsustainable upward climb. As noted, incorporating personalized medicine into the fabric of the health care system can help decrease costs associated with many embedded inefficiencies, such as trial-and-error dosing, hospitalizations due to adverse drug reactions, late- stage health condition diagnoses, and reactive treatment. Personalized medicine can also play an important role in the implementation of value-based payment and delivery models, which can help coordinate patient care and reduce costs.
As an example, data suggest that “As the biopharmaceutical industry investigates and earns FDA approval for more targeted pharmacogenomic testing therapies in oncology and other disease states, associated with the the benefits are clear: better diagnoses, fewer adverse drug reactions, increased patient management of dosing of the adherence, improved quality of life and, blood thinning drug warfarin ultimately, significant savings in overall U.S. health care costs.” can eliminate costs associated - Paul Hudson, CEO, Novartis Pharmaceuticals with hospitalizations for bleeding or thromboembolism. The Mayo Clinic and the pharmacy benefits manager Medco put the model to the test in a 3,600-subject prospective study. Hospitalization rates for heart patients were reduced by about 30 percent when genetic information was available to doctors prescribing the drug.33 Additionally, therapy guided by the Oncotype Dx® test has been estimated to provide a net cost savings of $2,256 per patient tested, based on a reduction in chemotherapy use with an incremental cost-effectiveness
32 Crespo-Leiro, MG, Sypmann, J, Shulz, U, et al. Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients. BMC Cardiovascular Disorders. 2015;15: 120.
33 Epstein, RS, Moyer, TP, Aubert, RE, et al. Warfarin genotyping reduces hospitalization rates. Results from the MM-WES (Medco-Mayo Warfarin Effectiveness Study). Journal of the American College of Cardiology. 2010;55: 2804-2812.
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ratio of $1,944 per life year saved.34 Another study found a $604 million annual savings among all patients when treatment with panitumumab (Vectibix®) or cetuximab (Erbitux®) was limited to patients with metastatic colorectal cancer whose KRAS gene was not mutated.35
34 Genomic Health. Validity Assessment of Oncotype Dx Breast Cancer Assay Economic Analyses. Accessed September 13, 2016 at http://breast-cancer.oncotypedx.com/en-US/Managed- Care/Health-Economics/Validity-Assessment.aspx. 35 Shankaran, V. Conference presentation at the Gastrointestinal Cancers Symposium. January 16, 2009. Accessed September 13, 2016 at http://www.medscape.com/viewarticle/586946. Requires free registration to access.
Science Policy | p. 65 The Case for Personalized Medicine 3
FIGURE 3: A NEW TREATMENT PARADIGM Without Personalized Medicine: Some Benefit, Some Do Not
Patients
Therapy
Some patients benefit, some patients do not benefit and some patients experience adverse effects.
With Personalized Medicine: Each Patient Receives the Right Medicine For Them
Patients
Biomarker Diagnostics
Therapy
Each patient benefits from individualized treatment
Adapted with permission from: PhRMA. A New Treatment Paradigm. Accessed September 13, 2016, at http://chartpack.phrma.org/personal-medicines-in-development-chartpack/a-new-treatment- paradigm/personalized-medicine-can-improve-efficiencies-within-the-health-care-system.
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SCIENTIFIC ADVANCEMENT
The science underpinning personalized medicine is driving new tests and therapies into the health care marketplace. Recent estimates by the genetic testing data company NextGxDx, for example, indicate that there are now no fewer than 65,000 genetic tests on the market (Figure 4), and L.E.K. Consulting estimates that the market value for drugs reliant on companion diagnostics was over $25 billion in 2015 (Figure 5). PMC counts 131 personalized medicines, that is, drugs that point to specific biomarker(s) in their labels to direct use, currently on the market (Figure 6).
These numbers are likely to continue growing. A recent study conducted by the Tufts Center for the Study of Drug Development showed that 42 percent of the drugs in the development pipeline now include biomarkers in their research and development design. The study also suggested that biopharmaceutical manufacturers have nearly doubled their R&D investment in personalized medicine over the past five years, and that these companies expect investment to increase by another 33 percent over the next five years (Figure 7).
On top of these developments, scientific advancements in genomic sequencing, how an individual’s biology impacts disease susceptibility, immunotherapy, and CRISPR- Cas9 are laying the groundwork for a new era in medical discovery.
Genomic Sequencing
It took $1 billion and 13 years to sequence the first draft of the human genome. Since then, sequencing technology has evolved from the manual Sanger method using radioactive labels to automated sequencing that employs color-coded fluorescent dyes. As a result, the cost of sequencing an entire genome has declined at a rate that exceeds Moore’s law (Figure 8). The results reflect a general trend in the industry and an important transition around mid-2007 brought on by next- generation sequencing technology.
Science Policy | p. 67 4 Introduction
FIGURE 4: PROGRESS BY THE THOUSANDS
Genetic Testing Products Currently on the Market* 65,839 (as of September 2016)
More Than 5,500 New Genetic Testing Products Came to Market Between April 2015 and September 2016*
Total Singles 5,768 Panels New Testing Products, April 2015–Sept 2016 (Cumulative growth)
APR MAY JUN JUL AUG SEP OCT NOV DEC JAN FEB MAR APR MAY JUN JUL AUG SEP
Source: NextGxDx. How Many Genetic Testing Products Are There? (#PMWC16). Accessed October 31, 2016, at https://blog.nextgxdx.com/2016/01/24/how-many-genetic-testing-products-are-there-pmwc16- infographic/. *Methodological Notes: NextGxDx began publishing the first reliable data on the number of genetic testing products available in January of 2016. NextGxDx estimates that there are more than 65,000 genetic testing products on the market. PMC has published a list of 127 genetic tests commonly associated with the 135 personalized medicines listed in Appendix B at http://www.personalizedmedicinecoalition.org/Education/Tests.
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The cost to sequence a human genome today, at approximately $1,000,36 is comparable to the cost of other medical tests and procedures, and new innovations may continue to drive sequencing costs down. Additional costs and time are necessary, however, for analysis and annotation in a clinical setting.
Human Biology and Disease Susceptibility: The Role of Genetics, Epigenetics and Proteins
Understanding the role of genetic “[Personalized medicine] gives us one of the variation in disease has become a greatest opportunities for new medical breakthroughs that we have ever seen.” central part of medical research. Most scientists believe that many - U.S. President Barack Obama common human ailments, such as heart disease, diabetes, and cancer, are significantly influenced by numerous rare genetic variations present within a single genome. Thus, one person might not carry the same set of variants as another, even if both have the same disease. These rare variants are, as National Institutes of Health (NIH) Director Francis Collins termed them, the “dark matter” in genetic patterns that remain undiscovered.
Thanks to the Human Genome Project and subsequent advancements in sequencing technology, the scientific community is now more equipped than ever to make sense of this “dark matter.” It is now possible to simultaneously interrogate hundreds of thousands of sites in an individual’s DNA to find associations between a given disease and genetic variation. In 2015, U.S. President Barack Obama launched the Precision Medicine Initiative (PMI), an effort to build a national research cohort of one million or more Americans who volunteer their genetic information for research aimed at finding more effective ways to improve health and treat disease. The project is poised to fill a tremendous gap in our understanding of human genetic
36 Illumina. Illumina Introduces the HiSeq X™ Ten Sequencing System. Accessed September 13, 2016 at http://www.businesswire.com/news/home/20140114006291/en/Illumina-Introduces-HiSeq- X%E2%84%A2-Ten-Sequencing-System.
Science Policy | p. 69 The Personalized Medicine Report 5
FIGURE 5: MARKETED THERAPEUTICS RELIANT ON A CDx GENERATED ~$25B IN THERAPEUTIC REVENUES IN 2015 Biopharma WW marketed CDx drug revenue segmentation (2015)* Percent of revenues
$25B $25B $25B 100 Other**** Other*** Therapy selection/ 80 monitoring Opdivo (BMS)
Tarceva (Roche)**
Perjeta (Roche)
60 Erbitux (BMS) Sprycel (BMS)
Tasigna (Novartis) Oncology
40 Therapy selection Gleevec (Novartis)
20 Herceptin (Roche)
0 Drug (Company) Therapeutic area Test purpose
* 2015 revenues are actual or analyst estimates; PHC products include those with labels that require/recommend CDx tests for candidacy ** Includes all Tarceva revenues, not just those from first-line treatment for EGFR+ NSCLC patients *** Other includes Alecensa, Aristada, Blincyto, Bosulif, Cholbam, Cotellic, Gilotrif, Ibrance, Iressa, Kadcyla, Lonsurf, Lynparza, Mekinist, Nucala, Orkambi, Praluent, Repatha, Rexulti, Selzentry, Tafinlar, Tagrisso, Tykerb/Tyverb, Vectibix, Victrelis, Xalkori, Zelboraf and Zykadia drug revenues **** Other includes Infectious Disease, Neurology, Cardiology, Pediatrics, Respiratory and Gastroenterology therapeutic areas Source: Republished with permission from L.E.K. Consulting, “Marketed Therapeutics Reliant on a CDs Generated ~$25B in Therapeutic Revenues in 2015,” PowerPoint presentation, Updated January 27, 2016, L.E.K. Consulting, Los Angeles
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variation by making thousands and ultimately a million genome sequences securely available for scientific interrogation.
But advances in personalized medicine are not confined to genetics. There is a growing understanding of genomic changes that can alter the chemistry and structure of DNA without altering its sequence. These “epigenetic” changes can occur in response to environmental factors, and influence whether certain genes are turned “on” or “off.” Epigenetic factors have been linked to a number of health conditions, including heart disease, diabetes, and cancer. The NIH has developed the Roadmap Epigenomics Project to study the role of epigenetics in human diseases.37
In addition, efforts coordinated by the NIH to standardize existing proteomic technologies such as mass spectrometry are leading to more robust identification of protein biomarkers, which indicate the presence or absence of disease apart from the risk prediction of genetic analysis. Entirely new approaches to protein biomarker detection38 are promising to make proteomics as “simple” as genetic analysis, ushering in an era when diseases can be diagnosed — and treated — in their earliest stages.
Immunotherapy
Researchers and pharmaceutical companies are also developing highly personalized treatment approaches that use the patient's own immune system to help fight cancer. These “immunotherapies” work in different ways. Some provide a general boost to the body’s immune system. Others help train the immune system to attack specific cancer cells by inhibiting a tumor’s ability to use a substance called PD-L1 to put the “brakes” on immune cells. Novel immune checkpoint inhibitors like pembrolizumab (Keytruda®) and nivolumab (Opdivo®), for example, block the
37 National Institutes of Health. Roadmap Epigenomics Project. Accessed September 13, 2016 at http://www.roadmapepigenomics.org/. 38 SomaLogic. SomaLogic. Accessed September 13, 2016 at http://www.somalogic.com/Homepage.aspx.
Science Policy | p. 71 6 Introduction
FIGURE 6: COMING OF AGE Number of Personalized Medicines Has Increased Steadily Since 2008*
131
106
81
36
5
2008 2010 2012 2014 2016
Sources: Personalized Medicine Coalition. The Case for Personalized Medicine (eds. 1–4). 2008–2014; Personalized Medicine Coalition. Applications: Therapies. Accessed October 31, 2016, at http://www. personalizedmedicinecoalition.org/Education/Therapies. *Methodological Notes: The number of personalized medicines was calculated by combining informa- tion from former editions of PMC’s Case for Personalized Medicine (2008–2014) with 2016 data from FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling, accessed October 31, 2016, at http:// www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm and CPIC’s Genes-Drugs tables, accessed October 31, 2016 at https://cpicpgx.org/genes-drugs/. A com‑ plete list of the 135 drugs counted in 2016 is available at http://www.personalizedmedicinecoalition.org/ Education/Therapies.
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ability of PD-L1 to bind with its receptor, PD-1, and have been approved for the treatment of melanoma, non-small cell lung cancer, kidney cancer, and Hodgkin lymphoma.39 40 They are also being studied for use against many other types of cancer.
Therapeutic cancer vaccines are another type of immunotherapy. These drugs direct an immune response against specific cancer cells. For example, sipuleucel-T (Provenge®) is a therapeutic vaccine to treat advanced prostate cancer in patients who are no longer being helped by hormone therapy. The treatment strategy involves activating a patient’s own T-cells against a prostate-specific protein antigen. Although the vaccine doesn’t cure prostate cancer, it can significantly shrink prostate tumors and help extend patients’ lives.
CRISPR/Cas9 Gene Editing
A new tool called CRISPR/Cas9 “[B]etween 2012 and 2016 we have invented gene editing is also generating technologies that allow us to change human excitement in personalized genomes intentionally and permanently … We can now ‘read’ human genomes, and we can medicine. The discovery of ‘write’ human genomes in a manner CRISPR (clustered regularly inconceivable just three or four years ago.” interspaced short palindromic - Siddhartha Mukherjee, M.D., Ph.D.,, Assistant Professor of Medicine, Columbia University repeats) and CRISPR-associated (Cas) genes has allowed for the development of efficient and reliable ways to make precise changes to the genome of living cells. Gene editing using the CRISPR/Cas9 technology may allow for the correction of disease-causing mutations in humans.41 The potential application of this technology for personalized treatment strategies spans a wide spectrum of health conditions, from congenital blindness to cancer. However, the potential of germ-line genetic modification has raised ethical concerns
39 Bristol-Myers Squibb. Opdivo. Accessed September 13, 2016 at http://www.opdivo.bmscustomerconnect.com/gateway. 40 Merck. Keytruda. Accessed September 13, 2016 at https://www.keytruda.com/. 41 Mukherjee, S. The Gene: An Intimate History. 2016: 12.
Science Policy | p. 73 The Case for Personalized Medicine 7
FIGURE 7: THE BIOPHARMACEUTICAL INDUSTRY IS HEAVILY INVESTED IN PERSONALIZED MEDICINE Personalized Medicine is rapidly coming of age. Drug development pipelines are full of new targeted treatments that offer hope of effective new treatment options for patients.
42% 73%
of all drugs in of oncology drugs development are in development are personalized medicines. personalized medicines.
Personalized Medicines
• 42% of all compounds—and 73% of oncology compounds—in the pipeline have the potential to be personalized medicines.
• Biopharmaceutical companies nearly doubled their R&D investment in personalized medicines over the past five years, and expect to increase their investment by an additional 33 percent in the next five years.
• Biopharmaceutical researchers also predict a 69% increase in the number of personalized medicines in development over the next five years.
Source: Tufts Center for the Study of Drug Development. Personalized medicine gains traction but still faces multiple challenges. Impact Report. 2015;17(3).
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about the appropriate use of the technology. These concerns are sure to lead to ethical debates going forward. Nonetheless, CRISPR/Cas9’s application to treatment of diseases targeting somatic cells in adult patients will likely have a significant impact on medical technology, as will many of the other trends described here.
Science Policy | p. 75 8 Introduction
FIGURE 8: THE RAPIDLY DECREASING COST OF SEQUENCING HUMAN GENOMES Average cost of sequencing a genome for NHGRI-funded sequencing technology projects over time. This graph captures the dramatic decline in sequencing costs through April 2013, and the cost has continued to drop.
$100M
$10M Moore’s Law
$1M
$100K COST PER GENOME COST $10K
$1K 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Source: National Human Genome Research Institute. The Cost of Sequencing a Human Genome. Accessed September 13, 2016, at http://www.genome.gov/sequencingcosts.
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REGULATORY POLICY
Scientific progress in “The concept of personalized medicine is not personalized medicine is new. The practice of medicine has always been about treating each individual patient, and driving an increase in the clinicians have long observed that different number of personalized patients respond differently to medical interventions. What is new is that paradigmatic medicine products and developments in science and technology offer services subject to regulatory new promise for developing targeted therapeutics and tools for predicting who will review. In fact, 28 percent of respond to a medical therapy or who will suffer the novel new drugs FDA ill effects.” approved in 2015 were - Margaret Hamburg, M.D., Former personalized medicines Commissioner, FDA (Figure 9). The agency has also responded to the growing demand for regulatory clarity by issuing draft guidance documents (Figure 10). The 21st Century Cures Act, which Congress passed in 2016, encourages the agency to modernize its paradigm for considering “real-world data,” the patient experience, and molecular pathways as they relate to clinical trial designs.
The landscape for regulation of personalized medicine, however, is still emerging. Among the topics under continued discussion are FDA’s proposed policies related to the regulation of personalized medicine tests, next-generation sequencing technologies and codeveloped personalized medicine products.
Personalized Medicine Tests
The emergence of personalized medicine tests that inform clinical decision-making and guide drug selection and dosage has led FDA to re-examine its approach to regulating diagnostics. Traditionally, diagnostic tests have fallen into two main categories: diagnostic kits and laboratory-developed tests (LDTs). The former are products containing all the reagents and materials needed to run the test, and are regulated by FDA as medical devices. Only a small portion of personalized medicine diagnostics falls under this category; most are LDTs.
Science Policy | p. 77 The Case for Personalized Medicine 9
FIGURE 9: PERSONALIZED MEDICINE AT FDA: THEN AND NOW Personalized medicines accounted for just 5 percent of FDA’s novel new drug approvals in 2005. Today, they account for more than 25 percent.
2005 2015
5% 28%
of FDA’s novel new of FDA’S novel new drug approvals were drug approvals were personalized. personalized.
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The clinical laboratories that perform LDTs are subject to the Clinical Laboratory Improvement Amendment (CLIA) rules administered and implemented by the Centers for Medicare and Medicaid Services (CMS).42 Clinical laboratories can obtain CLIA certification directly from CMS, typically through state agencies that survey labs for compliance with CLIA requirements. A lab can also seek accreditation by one of the independent accreditation organizations approved by CMS, which include the College of American Pathologists (CAP), among others. Although FDA has historically claimed jurisdiction to regulate LDTs, the agency has also historically refrained from actively regulating these tests, under a policy it describes as “enforcement discretion.”
In July of 2014, however, FDA outlined a framework for the agency’s oversight of LDTs. Following publication, many organizations conceded that a legislative solution would be required to adequately address concerns raised by the different sectors of the laboratory community. In 2016, following the election of U.S. President Donald Trump, FDA announced its decision to delay finalization of its guidance on the topic. The uncertainty surrounding the future of the regulatory landscape for LDTs continues to discourage investment in molecular diagnostics.
Regulatory Oversight of NGS-Based Diagnostic Tests
FDA is also struggling to understand how to regulate diagnostics that incorporate next-generation sequencing (NGS) technology, which yield insights on entire sets of genes. While current regulatory concepts are applicable for the regulation of conventional diagnostics that measure a limited number of substances associated with a disease or condition, diagnostic tests that use NGS technology can examine millions of DNA variants at a time, and require a more flexible approach to oversight relevant to the novel nature of these tests.
FDA is developing a new approach to regulating NGS tests that the agency says will allow timely access to tools that have adequate analytical and clinical performance.
42 Personalized Medicine Coalition. Pathways for Oversight of Diagnostics. 2013. Accessed September 13, 2016 at http://www.personalizedmedicinecoalition.org/Resources/Pathways_for_Oversight_of_Diagnostics.
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FIGURE 10: POLICY AND GUIDANCE DOCUMENTS FROM THE U.S. FDA
2005 Pharmacogenomic Data Submissions (final guidance) 2007 Pharmacogenomic Tests and Genetic Tests for Heritable Markers (final guidance) 2007 In Vitro Diagnostic Multivariate Index Assays (draft guidance) 2008 E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories (final guidance)
2011 E16 Guidance on Biomarkers Related to Drug or Biotechnology Product Development: Context, Structure, and Format of Qualifications Submissions (final guidance)
2013 Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for Labeling (final guidance)
2012 Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products (draft guidance)
2013 Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for Labeling (final guidance)
2014 Qualification Process for Drug Development Tools (final guidance) 2014 In Vitro Companion Diagnostic Devices (final guidance) 2014 Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) (draft guidance)
2014 FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs) (draft guidance)
2016 Use of Standards in FDA Regulatory Oversight of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Used for Diagnosing Germline Diseases (draft guidance)
2016 Use of Public Human Genetic Variant Databases to Support Clinical Validity for Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (draft guidance)
2016 Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product (draft guidance)
Source: U.S. Food and Drug Administration. http://www.fda.gov/RegulatoryInformation/Guidances/default.htm
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Through 2016, only one NGS instrument (Illumina MiSeqDx™) and two accompanying assays for the diagnosis of cystic fibrosis (Illumina MiSeqDx,™ Cystic Fibrosis 139 Variant and Clinical Sequencing Assays) have been FDA-approved. Because it was impractical to detect every possible variant that might exist in a genomic sequence, analytical test performance for the MiSeqDx™ system was demonstrated for a representative number of subsets of types of variants in multiple sequencing contexts.
The agency is considering extending this subset-based approach for other NGS platforms alongside other approaches for the establishment of analytic validity and clinical significance. Regarding analytical validity, one such approach is the development of methodological, quality-based standards that laboratories could use to establish analytical performance. In relation to clinical significance, FDA is considering an oversight approach wherein test developers may rely on clinical evidence from FDA-recognized public genome databases to support clinical claims for their tests and provide assurance of accurate clinical interpretation of test results. These approaches would be a significant departure from the agency’s traditional regulatory approach, which relies on a number of large randomized clinical trials to provide evidence of analytic and clinical validity of individual variants. In 2014, FDA issued a discussion document seeking public input on these novel regulatory approaches, and in 2016 the agency released two draft guidance documents describing potential processes for analytic standards development and FDA-recognized public genome database development. Many members of the personalized medicine community believe the processes outlined in the documents reflect FDA’s willingness to adapt to the changing landscape of medicine.
Codevelopment
According to FDA, “a companion diagnostic is an in vitro diagnostic or an imaging tool that provides information that is essential for the safe and effective use of a
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corresponding therapeutic product.”43 The need for a clear regulatory path for companion diagnostics has been a great concern for personalized medicine since the first therapeutic product with an accompanying diagnostic (Herceptin®) was approved six months apart from the diagnostic test (HercepTest™) in 1998. In 2014, FDA released its final In Vitro “CDER uses a lot of flexibility when reviewing Companion Diagnostic Devices applications for targeted drugs. For example, Guidance, which helped clarify among the targeted therapies approved in recent years… 90 percent used one or more of its method for conducting FDA’s expedited programs such as simultaneous reviews of a drug breakthrough, fast track, priority review and accelerated approval.” and its companion diagnostic.44 - Janet Woodcock, M.D., Director, Center for The guidance describes Drug Evaluation and Research, FDA conditions under which a targeted drug might be approved ahead of a corresponding diagnostic test. While these guidelines were in development, FDA, Health Canada, and the EMA had, in several cases, either mandated or recommended that biomarker testing be performed prior to prescribing certain drugs. Recognizing that the class of companion therapeutics/diagnostics is likely to grow, FDA has also begun publishing a table of genomic biomarkers that it considers valid in guiding the clinical use of approved drugs.45
43 U.S. Food and Drug Administration. List of Approved Companion Diagnostic Devices (In Vitro and Imaging Tools). Accessed September 13, 2016 at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm3014 31.htm.
44 U.S. Food and Drug Administration. Guidance for Industry and Food and Drug Administration Staff: In Vitro Companion Diagnostic Devices. 2014. Accessed September 13, 2016 at http://www.fda. gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM262327. pdf.
45 U.S. Food and Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labeling. Accessed September 13, 2016 at http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm.
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In mid-2016, FDA published an additional draft guidance document on codevelopment called Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product. The document explains how therapeutic and diagnostic partners should engage with the agency when codeveloping products, removing one regulatory hurdle to the parallel regulation of targeted therapeutics and their companion diagnostic tests.
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COVERAGE AND PAYMENT POLICY
Regulatory approval of personalized medicine products and services, however, is only part of the story. Coverage and payment policies — whether applicable to government programs like Medicare or private payers — play an equally important role.
Health care policy leaders “The top three issues in personalized medicine have contended that in order are reimbursement, reimbursement and reimbursement.” “to stimulate the development - Alexis Borisy, Partner, Third Rock Ventures of a more robust diagnostics pipeline and to harness the benefits of personalized medicine in patient-centered care delivery, policymakers must create an environment that encourages increased investment in diagnostics, enables new advances in patient care that are safe, accurate and reliable, and establishes a viable pathway toward patient access.”46 However, under pressure to address rising health care costs, policymakers and payers are increasingly considering policies that may result in across-the-board coverage and payment cuts, inadvertently discouraging continued developments in personalized medicine. Bringing personalized medicine to patients will depend on policymakers appreciating the personalized medicine value proposition in the context of emerging coverage and payment trends, which are affected by health technology and value assessment frameworks, procedural changes to the reimbursement landscape, and payment and delivery reforms.
Evidence Requirements
As discussed, personalized medicine offers many benefits to patients, including an improved capacity to prevent disease, more effective treatments, improved side- effect profiles, and reduced use of invasive testing procedures. By ensuring that only
46 Abernethy, A, Abrahams, E, Barker, A, et al. Turning the tide against cancer through sustained medical innovation: The pathway to progress. Clinical Cancer Research. 2014;20(5): 1081-1086.
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patients who will benefit from a particular intervention ultimately receive it, personalized medicine may also make the health care system more efficient. Payers, however, require convincing evidence of its clinical and economic value,47 and it is not clear how that evidence should be developed and disseminated for maximum impact. Insurance coverage of diagnostic tests, for example, will likely require practice-based evidence about their value. Obtaining the real-world data necessary for generating this evidence, however, is difficult unless the products and services in question are covered by insurance policies. These realities have led to a challenging conundrum in demonstrating the value proposition for personalized medicine. A solution is not yet apparent.
Value Assessment Frameworks
Multiple stakeholders have developed “value assessment frameworks” in recent years to measure the value of novel technologies, and these frameworks have begun to influence payer coverage and payment decisions. These frameworks, however, often fail to account for the heterogeneity of treatment effects. For example, in 2016, the Institute for Clinical and Economic Review (ICER), a nonprofit organization that uses available evidence to examine the value of therapeutics based on a conceptual framework that combines its estimation of the clinical value of a particular drug with several other factors, issued a value assessment determination on drugs for multiple myeloma that was largely based on population averages.48 Patient groups responded negatively to the report, noting a lack of consideration of the clinical benefit of a drug to certain patients. As the Multiple Myeloma Research Foundation pointed out in its letter to ICER, “the promise of precision medicine is that each patient is unique and will consequently respond to treatment differently based on
47 Novartis Oncology. The Precision Oncology Annual Trend Report: Perspectives From Payers, Oncologists, and Pathologists. 2016. 48 Institute for Clinical and Economic Review. Multiple Myeloma: Evidence Report. Accessed September 13, 2016 at https://icer-review.org/material/multiple-myeloma-evidence-report/.
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their particular genetic profile and further understanding of the biology of their disease.”49
The Changing Reimbursement Landscape
Significant challenges exist in establishing payment rates for diagnostic tests and targeted therapies that appropriately reflect the value they bring to care. Until recently, payments for diagnostic and molecular tests, the backbone of personalized medicine, were predictable and standardized, relying on payments based on “stacked codes.” However, recently, a number of coding and payment policy changes have led to significant changes in reimbursement for molecular diagnostic tests. CMS’ decision, for example, to use “gapfill” methodology, which allowed regional contractors to set prices for laboratory and molecular diagnostic tests, coupled with other payment decisions, has resulted in decreased payment rates for many personalized medicine tests. This, in turn, has placed a consistent downward pressure on physicians and laboratories interested in using novel, high-value molecular diagnostics to inform treatment decisions.
The 2016 Clinical Laboratory Fee Schedule (CLFS) final rule entitled “Medicare Program: Medicare Clinical Diagnostic Laboratory Tests Payment System,” which was part of the Protecting Access to Medicare Act (PAMA), implemented re-pricing and reporting requirements50 that further exacerbated the downward pressure on utilization of these technologies. This rule and a proposed Medicare Part B pilot program51 designed to reduce physician payment rates for prescribing practices are meant to try to reduce health care costs. These rules, however, largely lack
49 Patients Rising. The Multiple Myeloma Research Foundation (MMRF) Letter to ICER. Accessed September 13, 2016 at https://icerwatch.org/comments/multiple-myeloma-research-foundation- mmrf-letter-icer. 50 Federal Register. Medicare Program; Medicare Clinical Diagnostic Laboratory Tests Payment System. Accessed September 13, 2016 at https://www.federalregister.gov/documents/2016/06/23/2016- 14531/medicare-program-medicare-clinical-diagnostic-laboratory-tests-payment-system. 51 Centers for Medicare and Medicaid Services. Medicare Part B Drugs Payment Model. Accessed September 13, 2016 at https://innovation.cms.gov/initiatives/part-b-drugs.
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mechanisms that capture the value of targeted medicines, and may therefore threaten progress.
Payment and Delivery System Reform
CMS and private payers are also proposing new, “value-based” alternative payment models (APMs) that seek to drive improvements in care quality and efficiency, partially reacting to increasing demands to drive down health care costs. Understanding the changes and potential consequences these APMs will have on personalized medicine tests, pharmaceuticals, and companion diagnostics is essential to ensure continued progress in personalized medicine and improvements to patient care.
Traditionally, Medicare and private payers have paid for items and services on a fee- for-service basis, in which doctors, hospitals and other health care providers are paid for each unit of service provided. APMs are intended to pay providers for the value of the care that they provide, rather than the volume of services delivered. If implemented appropriately, APMs, such as Accountable Care Organizations (ACOs), value-based insurance design (VBID), medical homes, and clinical pathways, can improve health care by encouraging the adoption of personalized medicine. APMs should encourage physicians to tailor care based on an individual’s genetics and other factors, and support the adoption of novel targeted therapies. Accordingly, these models should include sufficient incentives to augment clinical care quality and not focus exclusively on cost control; ensure that patients have access to and are aware of all their diagnostic and treatment options; and encourage innovation that improves patient outcomes and quality of life.
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CLINICAL ADOPTION
Despite the steady increase in the number of clinically useful molecular diagnostics and targeted therapies on the market, the health care system has been relatively slow to integrate personalized medicine into clinical practice.52 Survey data shows, for example, that only four out of 10 consumers are aware of personalized medicine, and only 11 percent of patients say their doctor has discussed or recommended personalized medicine treatment options to them.53 Recent surveys have also shown that most health care organizations do not have formalized plans to leverage advances in genomics and data analytics to personalize patient care, and are unprepared to implement personalized medicine programs. 54 55
Recently, there have been a number of efforts to understand how to best encourage the efficient clinical adoption of personalized medicine. The National Academy of Medicine, for example, has issued several reports on translating genomic-based research to health care.56 57 58 The Personalized Medicine Coalition also assembled a
52 Abbasi, J. Getting pharmacogenomics into the clinic. JAMA. 2016;316(15): 1533-1535. 53 Miller, AM, Garfield, S, Woodman, RC. Patient and provider readiness for personalized medicine. Personalized Medicine in Oncology. 2016;5: 158-167.
54 Health Catalyst. Survey: Most Healthcare Organizations Unprepared for Precision Medicine. Accessed September 13, 2016 at http://www.prnewswire.com/news-releases/survey-most-healthcare- organizations-unprepared-for-precision-medicine-300206860.html. 55 Slabodkin, G. Many healthcare organizations not preparing for precision medicine. Health Data Management. January 27, 2011. Accessed September 13, 2016 at http://www.healthdatamanagement.com/news/many-healthcare-organizations-not-preparing-for- precision-medicine.
56 Institute of Medicine (US). Integrating Large-Scale Genomic Information into Clinical Practice: Workshop Summary. Washington DC. National Academies Press(2012). Available from: http://www.ncbi.nlm.nih.gov/books/NBK91500/ 57 Roundtable on Translating Genomic-Based Research for Health; Board on Health Sciences Policy; Institute of Medicine. Genomics-Enabled Learning Health Care Systems: Gathering and Using Genomic Information to Improve Patient Care and Research: Workshop Summary. Washington DC. National Academies Press(2015). Available from: http://www.ncbi.nlm.nih.gov/books/NBK316486/
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Health Care Working Group to develop a road map for integration of personalized medicine into health care.59 And the International Consortium on Personalized Medicine (IC PerMed) identified an index of barriers for clinical adoption.60
Integrating personalized medicine into health care requires: increasing awareness and understanding of personalized medicine concepts amongst the public and health care workforce; placing a greater emphasis on patient perspectives; recognizing the value of molecular pathways in guiding care; building new infrastructure and information management processes; and reshaping health care delivery to ensure access to personalized medicine technologies and services. To successfully integrate personalized medicine into health care, providers will need to implement a range of programs and processes (Figure 11) in each of these areas.
Education and Awareness
Perhaps the greatest challenge to integrating personalized medicine into health care is a lack of education and awareness among patients and throughout the health care delivery community. Freely available educational resources are being developed by a number of organizations61 62 63 64 65 that are presented in multiple formats based
58 Dzau, VJ, and Ginsburg, GS. Realizing the Full Potential of Precision Medicine in Health and Health Care. JAMA, published online September 26, 2016. 59 Pritchard, DE, Moeckel, F, Villa, M, Housman, L, McCarty, C, McLeod, HL. Strategies for Integrating Personalized Medicine into Health Care Practice. Personalized Medicine (2016) in press. 60 Horgan D, Jansen M, Leyens L et al (2014). An Index of Barriers for the Implementation of Personalized Medicine and Pharmacogenomics in Europe. Public Health Genomics, 17: 287-298. 61 Duke University School of Medicine. Educational Resources. Accessed September 13, 2016 at https://precisionmedicine.duke.edu/policy-resources/educational-resources. 62 Coriell Personalized Medicine Collaborative. Understanding Genetics. Accessed September 13, 2016 at https://cpmc.coriell.org/genetic-education/overview. 63 American Nurses Association. Personalized Medicine. Accessed September 13, 2016 at http://www.nursingworld.org/genetics. 64 National Human Genome Research Institute. Education. Accessed September 13, 2016 at https://www.genome.gov/education/. 65 Mayo Clinic. Genomics in Patient Care. Accessed September 13, 2016 at http://mayoresearch.mayo.edu/center-for-individualized-medicine/genomics-in-patient-care.asp.
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FIGURE 11: PRINCIPLES FOR INTEGRATING PERSONALIZED MEDICINE INTO HEALTH CARE
1. Healthcare providers, payers, employers, and policymakers, as well as patients and their families, need to have a better understanding of personalized medicine concepts and technologies.
2. Policies and practices related to patient engagement, privacy, data pro- tections, and other ethical, legal, and societal issues regarding the use of individual molecular information must ensure appropriate consent and be acceptable to patients.
3. Best practices must be established; for the collection and dissemination of evidence needed to demonstrate clinical utility of personalized medicine and ensure the recognition of its value to care.
4. Effective healthcare delivery infrastructure and data management systems should be developed and applied so that individual patient and clinical sup- port information is comprehensive, useful, and user-friendly, and so that it can be used to guide clinical decisions.
5. Best practices for health care delivery approaches, processes, and program operations that ensure access to personalized medicine must be established and implemented.
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on the needs of different stakeholders. However, they must be accurate, trusted, and updated regularly. PMC continues to work with the personalized medicine community to develop a content-rich website that can serve as the “go-to” source for personalized medicine knowledge. 66
Although many community education strategies are clear, building awareness and knowledge will not be easy, especially among physicians and other health care providers. In recognition of this reality, the Genomic Medicine Institute at Cleveland Clinic and others host CME-accredited genetics education symposia for practicing health care providers. The Mayo Clinic’s Center for Individualized Medicine educates members of the health care team and patients about personalized or genomics medicine and its implications in practice through professional development courses, conferences, and ongoing education that is integrated into practice.67
Patient Empowerment
The involvement of patients in their own treatment decisions and protection of their molecular information from being used in ways that would cause them concern, and, perhaps, long-term repercussions, such as discrimination, job loss, or loss of health insurance coverage are also critical for the clinical adoption of personalized medicine.
Many health and research organizations in the public and private sectors are reconsidering current policies related to patient privacy and consent for the use of molecular information. 68 69 Programs are being developed that will establish the
66 Personalized Medicine Coalition. Education. Accessed September 13, 2016 at http://www.personalizedmedicinecoalition.org/Education/Overview. 67 Mayo Clinic. Education & Training. Accessed September 13, 2016 at http://mayoresearch.mayo.edu/center-for-individualized-medicine/education-and-training.asp. 68 Garrison, NA, Sathe, NA, Antommaria, AHM, Holm, IA, Sanderson, SC, Smith, ME, McPheeters, ML, Clayton, EW. A systematic literature review of individuals’ perspectives on broad consent and data sharing in the United States. Genetics in Medicine. 2016;18: 663-671.
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necessary partnerships among industry suppliers, providers, and patients and their families to ensure that patient data are presented in ways that are meaningful to each of these groups while ensuring privacy. For example, biopharmaceutical development and commercial outsourcing services company Quintiles has initiated a Global Data Protection Program, which has issued global corporate policies for the “protection of personal information” and “data confidentiality” related to patient and proprietary information exchange between industry and providers.70
Perhaps most importantly, practitioners are recognizing that they need to regularly and appropriately involve patients in health care decision-making.71 Some providers are developing genetic counseling service policies to ensure that patients, early in their care, are able to understand their individual molecular information and its implications, so that they are able to make informed decisions regarding its disclosure and use before problems arise. 72 73 74
69 Bradbury, AR, Patrick-Miller, L, Domchek, S. Multiplex genetic testing: reconsidering utility and informed consent in the era of next-generation sequencing. Genetics in Medicine. 2015;17(2): 97–98.
70 Quintiles. Quintiles Global Data Protection Program. Accessed September 14, 2016 at http://www.quintiles.com/privacy/global-data-protection.
71 Fowler Jr., FJ, Levin, CA, Sepucha, KR. Informing and involving patients to improve the quality of medical decisions. Health Affairs. 2011;30(4): 699-706. 72 GenomeWeb. NIH pumps $15M into studies on effects of genomics information. GenomeWeb. May 18, 2016. Accessed September 13, 2016 at https://www.genomeweb.com/research-funding/nih- pumps-15m-studies-effects-genomics- information?utm_source=SilverpopMailing&utm_medium=email&utm_campaign=Daily%20News:% 20Foundation%20Medicine%20Sues%20Guardant%20Health%20for%20Patent%20Infringement %20-%2005/18/2016%2011:00:00%20AM. 73 Inova. MediMap™ PGx Testing at Inova. Accessed September 13, 2016 at https://www.inova.org/itmi/medimap. 74 Cigna. Cigna Builds on Three Years of Success, Expands Genetic Counseling Program. Accessed September 13, 2016 at http://www.businesswire.com/news/home/20160421006383/en/Cigna- Builds-Years-Success-Expands-Genetic-Counseling.
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Value Recognition
While many stakeholders believe that personalized medicine can provide benefits to patients and the health care system, payers and providers are still often reluctant to change policies and practices without convincing evidence of clinical and economic value. 75 To help build this evidence, the MolDX Program was initiated in 2011 by regional Medicare contractor Palmetto GBA to establish unique identifiers of molecular diagnostic tests to help facilitate claims processing and track utilization, as well as to establish clinical utility expectations and to complete technical assessments of published test data to determine clinical utility and coverage.76
Payers also need to understand financial and risk reduction endpoints within the body of evidence, along with patient survival and disease progression information. Strategies for addressing these challenges have begun to emerge. Forums between payers and product developers, for example, may facilitate a better understanding of the evidence requirements necessary for positive coverage determinations. In 2015, the Molecular Evidence Development Consortium (MED-C) was launched to help bridge the gap between payers, providers and industry in demonstrating the value of personalized treatment strategies by providing a forum to discuss and develop plans to gather molecular data on individual patients along with thorough information about their treatments and clinical outcomes.77
Infrastructure and Information Management
Effectively managing the massive amount of information associated with personalized medicine and coordinating programmatic processes and services related to its use are also major areas of need. Health care providers emphasize the need for data management processes that are straightforward, user-friendly, and
75 Novartis Oncology. The Precision Oncology Annual Trend Report: Perspectives From Payers, Oncologists, and Pathologists. 2016.
76 Palmetto GBA. Palmetto GBA MolDx. Accessed September 14, 2016 at http://www.palmettogba.com/moldx. 77 MED-C. MED-C. Accessed September 14, 2016 at https://med-c.org/.
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save time for the health care workforce. Institutional personalized medicine program policies and processes also need to be coordinated across research and clinical programs. Many organizations are committed to overcoming challenges in these areas, but strategies need to be developed and implemented widely in order to have a meaningful impact on the larger health care system. The Human Genome Research Institute’s Electronic Medical Records and Genomics Network (eMERGE), for example, has addressed the uptake of genetic information in electronic health record systems for genomic discovery and genomic medicine implementation research.78
Some health care delivery organizations that have begun to implement personalized medicine programs are working with information management organizations to develop data management systems that function directly within electronic health records to alert treating physicians about relevant biomarker information that could help inform treatment decisions. For example, community health care provider Intermountain Healthcare has teamed up with Syapse, a health information technology company, and N-of-One, a clinical interpretation management company, to enable community oncologists to access tumor genome profiling, analysis and drug procurement information through an integrated service platform.79
Ensuring Access to Care
Perhaps the most complex area of need is adapting health delivery approaches, processes and service structures to ensure access to personalized medicine. Clinical guidelines do not often reflect personalized medicine concepts. The PharmGKB and the Pharmacogenomics Research Network, however, recently established the
78 National Human Genome Research Institute. Electronic Medical Records and Genomics (eMERGE) Network. https://www.genome.gov/27540473/electronic-medical-records-and-genomics-emerge- network/. 79 GenomeWeb. Intermountain to use N-of-One’s clinical interpretation service for oncology. GenomeWeb. October 28, 2014. Accessed September 14, 2016 at https://www.genomeweb.com/informatics/intermountain-use-n-ones-clinical-interpretation- service-oncology.
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Clinical Pharmacogenetics Implementation Consortium (CPIC) to help develop updated pharmacogenomics clinical practice guidelines.80 Nonetheless, in many cases, overcoming challenges to adapting health care delivery approaches requires cultural change as well as the implementation of new programs. Progress will likely require shifting the perspectives of many stakeholders toward a personalized medicine paradigm, which can be accelerated by improving the knowledge base, empowering patients, demonstrating value across stakeholder groups, and building effective program infrastructure and information management processes. Most initiatives to accomplish these goals, however, are still in their infancy.
80 PharmGKB. Pharmacogenomics, Knowledge, Implementation; CPIC Clinical Pharmacogenetics Implementation Consortium. Accessed September 14, 2016 at https://www.pharmgkb.org/page/cpic.
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HEALTH INFORMATION TECHNOLOGY
Developing and providing access to novel personalized medicine products and services are only part of what is needed to achieve better human health by tailoring treatment based on the presence or absence of specific biomarkers. The health care system must also develop and implement health information systems that can capture, interpret, and share complex yet accurate patient data, including genomic information along with phenotypic and medical data.81 82 83 All of this requires providers to adopt powerful health information technology (IT) platforms that enable instant connections between real-world clinical results and molecular data so that providers can make clinical decisions based on a body of scientific knowledge that exceeds the training, experience, or memory of any single practitioner.
Integrating these kinds of health IT platforms at the point of care represents an ongoing challenge, but government support as well as the widespread use of electronic health records (EHRs) and mobile technologies may someday contribute to a “learning health care system” that could accelerate progress dramatically.
Government Support
Government support for health IT is strong. The Health Information Technology for Economic and Clinical Health (HITECH) Act, included as part of the American Recovery and Reinvestment Act of 2009 (ARRA), formalized the Office of the National Coordinator for Health Information Technology and established a funding stream for infrastructure and incentive payments to providers who adopt and use health IT in a meaningful way. Since 2015, hospitals and physicians face penalties for not using health IT. The passage of the ACA in 2010 accelerated the need for
81 National Center for Biotechnology Information. NCBI Retiring HapMap Resource. Accessed September 13, 2016 at http://hapmap.ncbi.nlm.nih.gov/. 82 IBM Corporation. Harnessing Big Data for Healthcare. Accessed September 13, 2016 at http://ibm.co/16dMOIk. 83 Intel. Compute for Personalized Medicine.
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change with unprecedented incentives and penalties that encourage hospitals to implement and utilize the EHRs in which molecular data are often stored.
Electronic Health Records
Now, with more than 80 percent of U.S. physicians using EHRs,84 85 the framework is in place (Figure 12) to leverage health IT investments and address ongoing concerns related to the clinical validity of endpoints, data interoperability, data sharing, and complex consent. Nonetheless, EHRs have remained essentially the same, and are ill- equipped to process biomarker information. Although EHR technology itself is advancing, there are ongoing challenges related to the technology’s ability to deliver data-driven health care. To help EHR developers expand functionality, Health Level Seven (HL7), an organization committed to developing international standards, created the Fast Health Interoperability Resources (FHIR) program in 2014. FHIR is a set of clinical concepts and resources designed to help EHR developers manage clinical data with ease.
Widespread use of EHRs allows researchers, test developers, and regulators to analyze the data they hold for a better understanding of the scientific underpinnings and real-world applications of personalized medicine. EHRs can be used effectively in longitudinal cohort studies, where the availability of a sufficient amount of high- quality data can enable retrospective analysis and better use of tests and tools for identifying health trends and predicting disease.
Mobile Technologies
The ubiquity of mobile information devices such as smartphones as well as advances in sensing technologies and self-management platforms may also provide important tools for personalized medicine. Several ongoing clinical trials feature
84 Accenture Consulting. Latest Thinking. Accessed September 13, 2016 at http://www.accenture.com/gb-en/Pages/insight-digital-doctor-is-in.aspx. 85 Accenture. EMR and HIE Use Increases Among U.S. Doctors, Accenture Annual Survey Finds. Accessed September 13, 2016 at http://newsroom.accenture.com/news/emr-and-hie-use-increases-among- us-doctors-accenture-annual-survey-finds.htm.
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FIGURE 12: TECHNOLOGICAL ADVANCES SINCE COMPLETION OF THE HUMAN GENOME PROJECT
2003 2015 Genome Sequencing Cost to Generate a Human Genome Sequence $54 million1 $1,0002 (excluding cost of analysis) Time to Generate a Human Genome Sequence 3–4 months1 1–2 days1 Number of Human Genomes Sequenced Annually 11 228,0003 Human Genetics Number of Genes with Known Phenotype/ 1,4741 2,9374 Disease-Causing Mutation Genomic Medicine Drugs Labeled with Pharmacogenomic Information 461 1315 Targeted Therapies Approved by FDA 36 547 Genetic Testing Products on Market 2–3 thousand8 60,4829 Basic EHR Use by Office-Based Physicians 17%10 83%11
1 National Human Genome Institute. Quantitative Advances Since the Human Genome Project (HGP). Accessed October 3, 2016, at https://www.genome.gov/images/illustrations/hgp_measures.pdf. 2 Veritas Genetics. myGenome. Accessed October 4, 2016, at https://www.veritasgenetics.com/mygenome. 3 According to Illumina President & CEO Francis de Souza. Source: Regalado, Antonio. EmTech: Illumina Says 228,000 Human Genomes Will Be Sequenced This Year. MIT Technology Review. September 24, 2014. Accessed October 4, 2016 at https://www.technologyreview.com/s/531091/emtech-illumina-says-228000-human-genomes-will-be-sequenced-this-year. 4 Chong, JX et al. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities. The American Journal of Human Genetics. August 6, 2015;97(2):199-215. Accessed October 4, 2016, at http://www.ncbi.nlm.nih.gov/ pubmed/26166479. 5 Estimated by Personalized Medicine Coalition. 6 L.E.K. Consulting. Recent Personalized Therapeutic Launches Have Relied on Well-Validated Biomarkers (BRAF, EGFR) and First- in-Class Biomarkers Including BRCA and PD-L1. PowerPoint presentation, updated January 27, 2016. Los Angeles, CA. Note: Includes only drugs with required or recommended biomarkers on label. 7 Personalized Medicine Coalition. 2015 Progress Report: Personalized Medicine at FDA. Accessed October 4, 2016, at http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/2015_Progress_Report_PM_at_FDA1.pdf. 8 Estimate based on gene tests. See Gene Tests. Disorders for which genetic tests are available and laboratories offering tests 1993–2016. Accessed October 11, 2016, at https://www.genetests.org. 9 NextGxDx. The Complex, Growing World of Genetic Testing. Accessed October 4, 2016, at http://docs.nextgxdx.com/genetic- testing-infographic.jpg. Note: Only includes US-based CLIA-certified labs. 10 Hsiao Ph.D., Chun-Ju and Esther Hing, M.P.H. Use and Characteristics of Electronic Health Record Systems Among Office-based Physician Practices: United States, 2001–2013. NCHS Data Brief No. 143 (January 2014). U.S. Department of Health and Human Services. Available at http://www.cdc.gov/nchs/data/databriefs/db143.pdf. 11 The Office of the National Coordinator for Health Information Technology. Office-based Physician Electronic Health Record Adoption: 2004–2014. Health IT Quick-Stat #50. Accessed October 4, 2016, at http://dashboard.healthit.gov/quickstats/ pages/physician-ehr-adoption-trends.php
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the use of wearable and environmental sensors to learn how to deliver real-time care to patients.86 For example, some patients with type 2-diabetes are getting their blood-glucose level data via mobile measurement, while having it continually updated and graphed on their smartphone or tablet. As a result, these patients are far more engaged in their own personalized medical care.87
A “Learning Health Care System”
EHRs and mobile technologies “You have to create a system where you have may someday enable a “learning the patients’ permission to follow them health care system” that throughout their lifetimes so that you can define the populations for whom a particular systematically captures, technology or treatment is beneficial.” analyzes and shares findings - William S. Dalton, Ph.D., M.D., CEO, M2Gen, from every clinical interaction Director, DeBartolo Family Personalized Medicine Institute at Moffitt Cancer Center and research milestone into a continuous feedback loop. Linking clinical outcomes to new research on genetic and other molecular variation has two benefits: (1) physicians receive clinical decision support tools and (2) data on personalized diagnostics and treatments can support a rational basis for insurance coverage.
In addition to the adoption of health IT, a successful learning health care system requires active patient engagement, collaboration among providers and researchers within and across institutions, and policies that incentivize knowledge sharing. Leveraging health IT and fostering better collaboration among researchers, physicians, and patients will support the transition to a continuous learning health care system that aligns emerging science and data with clinical decisions.
86 Shaw, RJ, Bonnet, JP, Modarai, F, George, A, Shahsahebi, M. Mobile health technology for personalized primary care medicine. The American Journal of Medicine. 2015;128(6): 555-557. 87 Topol, E. Getting doctors in sync with patients and mhealth. Hospitals & Health Networks. February 20, 2014. Accessed September 13, 2016 at http://www.hhnmag.com/articles/5099-getting-doctors- in-sync-with-patients-and-mhealth.
Science Policy | p. 99
CONCLUSION
The long arc of medical history has been one in which diagnostic capability has evolved from the metaphysical to the anatomical to the cellular and ultimately to the molecular level. Now that diseases can be sub-classified into categories that indicate the course of disease and its likely response to treatment — using evidence well beyond what is visibly obvious — there is an obligation to act on that information.
Technology continues to lead, with genomic sequencing and other molecular measurements likely to join other “democratized” technologies — a computer on every desk, a cell phone in every pocket, and someday a genomic sequence in every medical record. The result: We will likely continue to generate significantly more information than we are prepared to act upon.
To keep up with the “Personalized medicine stands right at the technology, serious effort will center of [the health care] revolution, with the be required from every corner science enabling greater precision that not only can improve the lives of patients, but can also of the health care spectrum. create efficiencies within the health care system Regulatory authorities must by delivering the right treatment to the right patient at the right time.” establish a clear set of guidelines for evaluating and - Stephen J. Ubl, President and CEO, PhRMA approving personalized drugs and, significantly, the diagnostics that identify patients who can benefit from them. Translational research must identify the benefits of personalized medicine technologies. Medicare and private insurers must establish a path toward evaluating the clinical and economic utility of personalized medicine practices in order to facilitate their reimbursement. Health care delivery organizations must successfully integrate personalized medicine into clinical practice. Patients must participate in their own health care choices, taking an active role in expressing their concerns about data sharing and access to personalized treatments. Finally, health information systems must incorporate features that support 21st century medicine, providing the ability to collect and analyze data from everyday clinical encounters
Science Policy | p. 100
and helping physicians make decisions based on the vast amount of information linking genetic patterns to diseases and their treatment.
Scientific discovery in personalized medicine will continue to grow, and this represents a great opportunity for our generation. To make this a reality is going to require the combined resources of multiple stakeholders — all of whom must be willing to invest in a paradigm change that can preserve innovation, improve outcomes, and reduce the overall costs of health care. In order to sustain continued advances in personalized care and treatment, emerging approaches for value assessment must evolve with the rapid pace of science and reflect important differences among patients. In short, to reap the benefits of personalized medicine, policymakers must create an environment that encourages increased investment in diagnostics and targeted drugs, enables new advances in patient care that are safe, accurate and reliable, and establishes a viable pathway toward patient access.88
Much work remains to be done in building the infrastructure for personalized medicine, but the resources we invest in completing the task now will enable us to seize the opportunity from the new developments in science and technology and realize the full health and economic benefits of matching the right treatment or prevention to each and every patient.
88 Abernethy, A, Abrahams, E, Barker, A, et al. Turning the tide against cancer through sustained medical innovation: The pathway to progress. Clinical Cancer Research. 2014;20(5): 1081-1086.
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9. Communications Impact Report 2016
Please see separately-bound report.
The 2016 Impact Report can be downloaded here: http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/2016-Impact-Report.pdf
Communications | p. 1
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Communications | p. 2
PRESS RELEASES 2016
*** Bolded items are included after this list. ***
1. “More Than 1 in 4 Novel New Drugs Approved by FDA in 2015 are Personalized Medicines” January 21, 2016
2. “PMC Welcomes Appointment of Robert M. Califf, M.D., M.A.C.C., as FDA Commissioner” February 24, 2016
3. “Coalition Commends White House on Precision Medicine Initiative, Encourages Continued Progress in Regulation, Reimbursement” February 25, 2016
4. “Coalition Commends National Institutes of Health on Selection of Eric Dishman as Director of Precision Medicine Initiative Cohort Program” April 11, 2016
5. “PMC to Recognize Raju Kucherlapati With 12th Annual Leadership in Personalized Medicine Award” June 29, 2016
Communications | p. 3
6. “PMC Commends ICER for Extending Public Comment Period for Scope of Work in Non-Small Cell Lung Cancer” July 1, 2016
7. “Coalition Applauds Progress on Precision Medicine Initiative, Encourages Additional Efforts in Regulation, Reimbursement” July 7, 2016
8. “PMC Commends ‘Moonshot’ Panel for Recognizing Personalized Medicine’s Importance in Research Recommendations, Encourages Complementary Efforts From Policymakers” September 7, 2016
Communications | p. 4
FOR IMMEDIATE RELEASE
Contact: Christopher J. Wells Personalized Medicine Coalition [email protected] 202-589-1755
PMC to Recognize Raju Kucherlapati With 12th Annual Leadership in Personalized Medicine Award
WASHINGTON (June 29, 2016) – On Nov. 17, 2016, the Personalized Medicine Coalition (PMC) will present its 12th Annual Leadership in Personalized Medicine Award to Raju Kucherlapati, Ph.D., Paul C. Cabot Professor of Genetics at Harvard Medical School, in recognition of his efforts to accelerate progress in personalized medicine through a range of initiatives in science, business and policy.
In a letter nominating him for the award, Stephen L. Eck, M.D., Ph.D., Vice President, Oncology Medical Sciences, Astellas Pharma Global Development, praised Kucherlapati’s organizing the Personalized Medicine Conference at Harvard Medical School, noting that “absent Raju’s dedication and leadership, the shift in medical care to personalized medicine would have taken a decade longer.”
Kucherlapati has had an outsized impact on personalized medicine.
His scientific achievements include contributions to the first mapping and sequencing of an entire human genome, which many believe was a stepping stone for medicine’s move toward personalized medicine. Kucherlapati’s work on that project was focused on human chromosome 12. He has also contributed to developments in gene targeting and homologous recombination, and developed a large number of mouse models for human disease as well as several techniques for modifying genes in mammalian cells and cloning human disease genes. The author of more than 450 peer-reviewed publications and a former member of the editorial board at The New England Journal of Medicine, Kucherlapati is widely regarded as one of the world’s leading geneticists.
He is also an entrepreneurial business leader who holds 12 patents. He has served as a co-founder or board member for a wide array of personalized medicine companies, including Abgenix, AVEO Pharmaceuticals, Cell Genesys, KEW Group, Metamark Genetics and Millennium Pharmaceuticals.
His contributions to the policy arena are no less impressive. He is a former member of the National Advisory Council for Human Genome Research at the National Human Genome Research Institute and served as co-chair of the steering committee for the National Cancer Institute’s Mouse Models for Human Cancer Consortium. He currently serves on the Presidential Commission for the Study of Bioethical Issues and is a member of the National Cancer Institute’s Cancer Genome Atlas program as well as the National Academy of Medicine.
Communications | p. 5
Kucherlapati remains enthusiastic about the personalized medicine community’s collaborative efforts to improve patient care and the health care system through personalized medicine.
“I am honored and humbled by this recognition by PMC, the organization that has done so much to advance personalized medicine and to bring together a diverse set of organizations and individuals to promote this important field,” Kucherlapati said.
Third Rock Ventures Partner Mark Levin, who also nominated Kucherlapati for the award, said his unqualified willingness to contribute to projects that could improve medicine is what sets him apart.
“Whatever he can do to make a difference, Raju will be there,” Levin wrote. “No one is more deserving.”
PMC will present the award to Kucherlapati at 1:45 p.m. on the second day of the 12th Annual Personalized Medicine Conference, which takes place at Harvard Medical School.
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About the Personalized Medicine Coalition: The Personalized Medicine Coalition (PMC), representing innovators, scientists, patients, providers and payers, promotes the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system. For more information about PMC, visit www.personalizedmedicinecoalition.org.
About the Leadership in Personalized Medicine Award: The Leadership in Personalized Medicine Award recognizes an individual whose contributions in science, business and/or policy have helped advance the frontiers of personalized medicine.
Previous recipients include:
• Janet Woodcock, M.D., Director, U.S. Food and Drug Administration Center for Drug Evaluation and Research • Elizabeth G. Nabel, M.D., former Director, National Heart, Lung and Blood Institute, National Institutes of Health • Ralph Snyderman, M.D., Chancellor Emeritus, Duke University • Michael O. Leavitt, former Secretary, U.S. Department of Health and Human Services • Brook Byers, Founding Member, Kleiner Perkins Caufield & Byers • William S. Dalton, Ph.D., M.D., President and CEO, Moffitt Cancer Center • Leroy Hood, M.D., Ph.D., President and Co-founder, Institute for Systems Biology • Randal W. Scott, Ph.D., Founder, Genomic Health Inc., Chairman and CEO, InVitae • Kathy Giusti, Founder and CEO, Multiple Myeloma Research Foundation • Mark Levin, Co-founder and Partner, Third Rock Ventures • Francis S. Collins, M.D., Ph.D., Director, National Institutes of Health
For more information, visit http://www.personalizedmedicinecoalition.org/About_Us/PMC_Award_for_Leadership_in_Personalized_Medicine.
Communications | p. 6
FOR IMMEDIATE RELEASE
Contact: Christopher J. Wells Personalized Medicine Coalition [email protected] 202-580-9780
PMC Commends ICER for Extending Public Comment Period for Scope of Work in Non-Small Cell Lung Cancer
PMC President: ICER 'Has a Responsibility' to Provide Adequate Time for Public Comment
WASHINGTON (July 1, 2016) – The Personalized Medicine Coalition (PMC) today commends the Institute for Clinical and Economic Review (ICER) for providing an additional week for public comments on a document related to the scope of ICER's work in non-small cell lung cancer (NSCLC).
ICER announced the extension three days after PMC joined other stakeholders in expressing concern about the organization's comment timelines. After meeting with ICER Director of Health Economics Rick Chapman, Ph.D., during a PMC policy committee meeting last week, the Coalition suggested that ICER provide a 30 - 60 day window for public comments.
"Given the significant attention ICER's assessments receive and the recent proposal by CMS to rely on ICER's value standards in the Part B payment demonstration, we believe ICER has a responsibility to allow additional time for stakeholders to provide thorough, thoughtful feedback on the scoping document as well as the draft evidence report," PMC President Edward Abrahams wrote in a comment letter on ICER's draft scoping document for NSCLC.
Abrahams noted in PMC's letter to ICER that federal agencies like FDA and CMS typically provide 30 - 60 days for public comments on significant policy documents. ICER's doing so would give PMC and other organizations enough time to evaluate how its value assessments might impact personalized medicine, which is the focus of President Obama's Precision Medicine Initiative and a key aspect of Vice President Biden's Cancer Moonshot Task Force.
In a blog posted yesterday morning, PMC Executive Vice President Amy M. Miller, Ph.D., said PMC looks forward to continuing its engagement with ICER.
"Because ICER plays a unique role in health policy, with health plans being the primary audience for their work, PMC will suggest improvements to ICER’s system to ensure that resulting work accounts for the challenges involved in assessing value of treatments that work for specific subgroups of patients,” Miller wrote.
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Communications | p. 7
About the Personalized Medicine Coalition: The Personalized Medicine Coalition, representing innovators, scientists, patients, providers and payers, promotes the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system. For more information about PMC, please visit www.personalizedmedicinecoalition.org.
Communications | p. 8
FOR IMMEDIATE RELEASE
Contact: Christopher J. Wells Personalized Medicine Coalition [email protected] 202-580-9780
Coalition Applauds Progress on Precision Medicine Initiative, Encourages Additional Efforts in Regulation, Reimbursement
WASHINGTON (July 7, 2016) – The Personalized Medicine Coalition (PMC) today applauds the Obama administration for steps it announced last night to further the Precision Medicine Initiative (PMI). PMC President Edward Abrahams said these steps are “important but insufficient to advance personalized medicine as fast as patients wish.”
As part of the administration’s work on the PMI, the National Institutes of Health (NIH) has awarded $55 million to health care provider organizations, technology developers and community health centers to establish the necessary infrastructure to build and leverage a cohort of one million volunteers. In addition, the U.S. Food and Drug Administration (FDA) has released draft guidance documents on the oversight of next-generation sequencing (NGS) tests.
Abrahams applauded these initiatives and said he agrees with Obama, whose op-ed in today’s Boston Globe states that "precision medicine gives us the chance to marry what’s unique about America — our spirit of innovation, our courage to take risks, our collaborative instincts — with what’s unique about Americans — every individual’s distinctive genetic makeup, lifestyles and health needs.”
But, Abrahams said, fulfilling that promise will also require broader regulatory changes that encourage innovation as well as supportive reimbursement policies. The Centers for Medicare and Medicaid Services (CMS), he said, has often been reluctant to pay for the personalized diagnostics and therapies the administration champions.
PMC is not the only stakeholder arguing for additional efforts in regulation and reimbursement. In an editorial published by Science in April of this year, Harold Varmus, M.D., former director of the U.S. National Cancer Institute, recommended that the administration "exercise its regulatory authority — most potently, to direct [CMS] to allow reimbursement for molecular profiling of cancers.” Varmus argues that doing so would "vastly increase the data available for analysis, accelerate interpretation of genetic profiles, provide a test bed for true sharing of clinical information and allow future coverage determinations by CMS to be made more quickly and sensibly.”
"The Obama administration is right to focus resources on developing and aggregating data and streamlining regulation for NGS tests,” Abrahams said. "But unless ongoing efforts to demonstrate the value of personalized medicine to patients and the health system are supplemented by public policies that encourage its advancement, progress will be slower than we would like.”
Communications | p. 9
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About the Personalized Medicine Coalition: The Personalized Medicine Coalition (PMC), representing innovators, scientists, patients, providers and payers, promotes the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system. For more information about PMC, visit www.personalizedmedicinecoalition.org.
Communications | p. 10
FOR IMMEDIATE RELEASE
Contact: Christopher J. Wells Personalized Medicine Coalition [email protected] 202-580-9780
PMC Commends ‘Moonshot’ Panel for Recognizing Personalized Medicine’s Importance in Research Recommendations, Encourages Complementary Efforts From Policymakers
WASHINGTON (September 07, 2016) – The Personalized Medicine Coalition (PMC) today commends the U.S. Cancer Moonshot's Blue Ribbon Panel for recognizing the importance of identifying which patient populations will benefit from the most promising cancer treatments in its recommendations for accelerating progress in the field.
PMC President Edward Abrahams said the recommendations, which were released this morning, recognize personalized medicine’s significance to the future of cancer care. He also said he appreciates the panel’s focus on research but encouraged policymakers to also align all public policies, notably in regulation and reimbursement, to accelerate investment in and adoption of the right cancer treatments for the right patients.
"The scientific community has established that in medicine and especially in oncology, one size does not fit all,” Abrahams said. "The future of the field therefore depends on our ability to identify which patients will benefit from which treatments. The panel clearly recognizes that.”
Data published in Tufts University’s Impact Report last year indicate that 73 percent of cancer drugs in development are associated with a diagnostic test to identify which patients can benefit from it, and most of the 10 recommendations listed in the panel’s Report at a Glance explicitly recognize the importance of understanding which treatments work for whom. In the concluding section, the authors note that their recommendations anticipate a future in which patients "obtain a genomic profile about their tumor, learn about what treatments might work best given their profile, and find other relevant information, including clinical trials, that may be important for them.”
Abrahams said PMC shares that vision for the future, and noted that the country’s regulation and reimbursement policies should be updated to prepare for it.
"As we know, unless we align public policies around promoting personalized medicine, notably in the regulatory and reimbursement arenas, progress in fighting cancer will be much slower than we would like,” Abrahams said.
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About the Personalized Medicine Coalition: The Personalized Medicine Coalition, representing innovators, scientists, patients, providers and payers, promotes the understanding and adoption of personalized medicine concepts, services
Communications | p. 11
and products to benefit patients and the health system. For more information about PMC, please visit www.personalizedmedicinecoalition.org.
Communications | p. 12
MEMBER UPDATES 2016
*** Bolded item is included as an example after this list. ***
1. “Developments Cap Extraordinary Year for the Field” January 4, 2016
2. “White House Announces New Effort to ‘End Cancer’” January 19, 2016
3. “Moonshot Ignites National Dialogue on NGS Coverage” February 1, 2016
4. “NextGxDx Identifies Over 60,000 Genetic Tests on Market” February 16, 2015
5. “Community Considers PMI’s Policy Implications” March 1, 2016
6. “CMS Proposal May Threaten Personalized Medicine” March 14, 2016
7. “Negligence Suit Fuels LDT Interpretation Controversy” March 28, 2016
Communications | p. 13
8. “New Report: APMs Should Incentivize Innovation” April 18, 2016
9. “Study Strengthens Economic Argument for Personalized Medicine” May 2, 2016
10. “’Moonshot’ Executive Director: ‘It’s Hundreds of Cancer’” May 16, 2016
11. “BIO Releases Groundbreaking Study” June 1, 2016
12. “Agency Makes Key Alterations in Final Rule” June 21, 2016
13. “Stakeholders Spotlight Ongoing Policy Challenges” July 18, 2016
14. “Results Billed as Win for Personalized Medicine Business Model” August 11, 2016
15. “Survey Shows Majority of Americans Support PMI” September 6, 2016
16. “Vice President Would Expect to Lead Cancer Moonshot ‘From Outside’ Under Clinton Administration” September 19, 2016
17. “Dr. Allen Roses Dies at 73” October 11, 2016
Communications | p. 14
18. “12th Annual Personalized Medicine Conference Preview” October 31, 2016
19. “House to Vote on 21st Century Cures Bill Today” November 30, 2016
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Communications | p. 16 November 30, 2016 Edition
HOUSE TO VOTE ON 21ST CENTURY CURES BILL TODAY
Precision Medicine Initiative, Cancer Moonshot, Access Provisions Could Help Speed Progress in Personalized Medicine
The U.S. House of Representatives is expected to vote this afternoon on a revised version of H.R. 6, the "21st Century Cures Act," which is designed to accelerate the pace of biomedical innovation. PMC President Edward Abrahams says the bill's provisional
Rep. Fred Upton (R-MI) and Rep. Diana funding for the Precision Medicine Initiative DeGette (D-CO) have spearheaded the effort and Cancer Moonshot as well as on the 21st Century Cures bill. provisions to speed patient access to innovative therapies based on molecular pathways could help advance personalized medicine.
"The 21st Century Cures bill supports personalized medicine," Abrahams said. "The Precision Medicine Initiative, the Cancer Moonshot and speedier access to innovative therapies based on molecular pathways, in particular, will all contribute to a healthier nation. We call on Congress to pass the bill and to ensure that these important programs are funded next year."
The 21st Century Cures bill authorizes $4.8 billion in funding over 10 years for the National Institutes of Health and $500 million for FDA, and also includes provisions that require FDA to make the patient experience a more central part of the drug development process and implement a variety of efforts to accelerate innovation. It includes provisions related to FDA's oversight of diagnostics, but does not address the regulation of laboratory-developed tests. NPR H.R. 6 — The 21st Century Cures Act
POLICY
Regulatory Landscape for Personalized Medicine Still in Flux as
FDA Holds Off on Finalizing Lab-Developed Test Guidance Communications | p. 17 In a move that leaves the regulatory environment for molecular diagnostics in flux, FDA has announced that it will delay the release of its final guidance on the regulation of laboratory-developed tests (LDTs) for the time being. Elizabeth Mansfield, Ph.D., Deputy Office Director, Personalized Medicine and Molecular Genetics, Office of In Vitro Diagnostics and Radiological Health, FDA, told Daryl Pritchard, Ph.D., Vice President, Science Policy, PMC, earlier this month that the agency understands "how important it is that we continue to work with stakeholders, our new Administration and Congress to get our approach right."
The agency released a draft guidance on the topic two years ago, and has consistently confirmed its intent to finalize the draft until this month, when Alberto Gutierrez, Ph.D., Director, Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiological Health, FDA, told the audience at the 12th Annual Personalized Medicine Conference that it was too early to tell how the election of Donald Trump may impact FDA's work on LDT oversight.
American Clinical Laboratory Association President Alan Mertz applauded FDA's decision to delay release of the final guidance.
"Today's announcement by the FDA has paved the way for a transparent discussion on meaningful reform that would protect diagnostic innovation and patient access," Mertz said. "The clinical laboratory community looks forward to working with all stakeholders as diagnostic innovation continues to be front and center in the advancement of medical science."
Mansfield will meet with PMC's members at the Coalition's Policy Committee Meeting on December 7. GenomeWeb (subscription content)
CMS' Final 2017 Pricing Decisions Improve Reimbursement Landscape for Personalized Medicine
In decisions that help improve the challenging reimbursement landscape for diagnostics that advocates say is curbing investment in personalized medicine, the Centers for Medicare and Medicaid Services (CMS) have responded to the community's requests for increased payment rates for several genomic tests.
In September, CMS issued its preliminary 2017 pricing determinations, which included reduced payment rates for molecular diagnostics including CareDx's AlloMap and Genomic Health's Oncotype Dx. These and other personalized medicine companies lobbied for increased rates for their products, and PMC cautioned CMS in a comment letter that the low rates "threaten the sustainability of the laboratory industry and continued investment in the developing field of personalized medicine." CMS raised the rates for AlloMap, Oncotype Dx and a host of other diagnostic products in its final determinations.
"We applaud CMS' decision to step in and reverse the proposed reduction in reimbursement for AlloMap," said Peter Maag, Ph.D., President, CEO, CareDx, and Communications | p. 18 PMC board member. "This decision ensures that heart transplant patients and physicians will continue to benefit from the only non-invasive surveillance solution on the market. It is also consistent with the Precision Medicine Initiative that supports medical innovation and improving medical care." GenomeWeb (subscription content) CareDx press release
NEWS
12th Annual Personalized Medicine Conference Participants Say 'Standard of Care' Still Falls Short
Convening just one week after the U.S. Presidential election, participants at the 12th Annual Personalized Medicine Conference renewed their commitment to advancing the field. The current treatment paradigm, they said, often fails to meet the needs of patients.
"Standard of care is not good enough," Michael Pellini, M.D., CEO, Foundation Medicine, said during the conference. "It's just not."
Conference speakers offered reasons to be optimistic about the future. The respective leaders of Joe Biden's Cancer Moonshot Task Force and President Obama's All of Us Research Program, for example, indicated that personalized medicine has bipartisan support in Congress, and the six payers who spoke at the event signaled a willingness to engage the community on the topic. The latter breakthrough was especially encouraging, as some speakers indicated that the current reimbursement environment is even more challenging than the confused landscape for the regulation of diagnostic tests, which has long been a problem for the field.
"The top three issues in personalized medicine are reimbursement, reimbursement and reimbursement," said Alexis Borisy, Partner, Third Rock Ventures.
Still, lingering uncertainty about President-elect Donald Trump's priorities colored many of the discussions. Trump has done little to clarify his intentions in health care, save for a short reference on his interest in maintaining a U.S. edge in health care innovation in a recent YouTube video republished by The Wall Street Journal.
"Whether its producing steel, building cars or curing disease, I want the next generation of production and innovation to happen right here in our great homeland," Trump said in the video. GenomeWeb (subscription content)
FDA's Approval of Exondys 51 Raises Questions About the Use of 'Surrogate' Measures in Trials for Personalized Medicines
FDA's recent approval of Exondys 51 as a treatment for the 13 percent of patients with Duchenne muscular dystrophy (DMD) who have a specific type of mutationCommunications in | p. 19 the dystrophin gene has raised new questions about the usefulness of the "surrogate" measures that have led to the accelerated approval of many personalized medicines.
Surrogate measures refer to data on indirect indicators of health outcomes such as tumor size and the presence or absence of specific proteins. Despite the fact that the drug was not proven to impact health outcomes like the ability to walk, FDA approved Sarepta's Exondys 51 on the basis of its ability to increase the levels of a protein called dystrophin, which is absent in the muscles of patients with DMD.
Critics say the decision weakens FDA's commitment to evaluating medicines based on their ability to impact health outcomes, but given the limited universe of patients with rare diseases like DMD who will also qualify for clinical trials to study the effectiveness of personalized medicines, some experts believe FDA will increasingly need to rely on surrogate measures to evaluate drugs for rare diseases. Accumulating enough patients to conduct a randomized trial, they say, will sometimes be impossible.
"The good news is we have precision medicine,” said Art Caplan, Ph.D., a bioethicist at New York University's Langone Medical Center. "The bad news is we have a regulatory system that is designed for imprecise medicine.”
Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research, FDA, defended the agency's approval of Exondys 51 at the 12th Annual Personalized Medicine Conference earlier this month. Quartz The Boston Globe
PMC in Nature: 'Personalized Oncology is Not an Illusion'
PMC President Edward Abrahams, Ph.D., and PMC Board Vice Chairman Stephen Eck, M.D., Ph.D., recently published a letter to the editor of Nature in response to the journal's highly publicized "Perspective" piece in which Vinay Prasad, M.D., M.P.H., of the Knight Cancer Institute at Oregon Health and Science University suggests that the failure of the National Cancer Institute's MATCH Trial demonstrates that personalized oncology "has not been shown to work." Prasad's piece, Abrahams and Eck say, ignores compelling evidence of personalized medicine's effectiveness.
"In our view, it is unreasonable to condemn personalized medicine for oncology on the basis of the limited success of a few trials," they write. "With more than 40 precision-oncology drugs on the market, such therapies are helping tens of thousands of U.S. patients by targeting specific molecular abnormalities." Nature
PMC NEWS
Coalition Plans Celebration of Amy Miller's New Role as CEO ofCommunications | p. 20 Society for Women's Health Research
PMC will celebrate with former Executive Vice President Amy M. Miller, Ph.D., as she prepares for her new role as CEO of the Society for Women's Health Research during the Coalition's Annual Holiday Party on December 7. In her more than a decade with PMC, Miller worked with innovators, scientists, providers and payers to help create a friendlier landscape for the field.
"Ten years ago, with only a small number of targeted therapies on the market, we were working to convince people that we were not overselling the concept of personalized medicine," Miller said. "Now, there are more than 100 targeted therapies on the market and diagnostics are playing a leading role in guiding their use. It has been a remarkable decade of progress for the field and the Coalition."
PMC's Holiday Party will take place at the Tabard Inn in Washington, D.C. Please email David Davenport at [email protected] to register. Society for Women's Health Research press release
MEMBER NEWS
PMC Welcomes New Member!
North Carolina Biotechnology Center The North Carolina Biotechnology Center accelerates life science technology-based economic development through innovation, commercialization, education and business growth. NC Biotech engages partners across the academic, business and economic development arenas to identify and support life science solutions that will benefit human health care and grow North Carolina's economy.
With its commitment to developing a precision health sector in North Carolina, NC Biotech established the North Carolina Precision Health Collaborative (NCPHC). The vision of this Collaborative is to advance transformative, data-driven precision health through innovation and partnership. The Collaborative’s mission is to accelerate initiatives that foster research, enable providers, engage industry and empower citizens to improve health outcomes and optimize resource utilization in North Carolina.
Bonnie J. Addario Lung Cancer Foundation Partners to Launch Unique Patient Data Registry
The Bonnie J. Addario Lung Cancer Foundation recently announced the launch of a patient data registry alongside the American Lung Association and AltaVoice. Unlike many registries, the joint effort is dynamic, global, open-sourced and pulls from multiple data sources.
"With 224,000 new lung cancer patients diagnosed in the U.S. every year, there is a dire need to improve patient outcomes and quality of life,” said Bonnie J. Addario,Communications | p. 21 chair and founder of the foundation. "We are proud to partner with the ALA and AltaVoice to turn lung cancer into a chronically managed disease by the year 2023.” Lung Disease News
Duke's Ralph Snyderman Publishes Insights on Integrating Personalized Medicine into Academic Health Centers
In a book titled A Chancellor's Tale: Transforming Academic Medicine, Duke University Chancellor Emeritus and James B. Duke Professor of Medicine Ralph Snyderman, M.D., offers insights on spearheading personalized medicine integration efforts at academic health centers. Snyderman led Duke University's effort to conceptualize and implement personalized medicine during his tenure as chancellor.
"The book describes the difficulties of making change in a complex academic institution including what worked, what went wrong and lessons learned," Snyderman writes on PMC's blog, Education & Advocacy. "My hope is that the personalized medicine community will find the stories interesting and my learning experiences useful." Education & Advocacy
Perthera, Lung Cancer Alliance Partner to Expand Patient Access to Personalized Medicine
Perthera and the Lung Cancer Alliance (LCA) recently announced a partnership through which the organizations hope to expand the number of lung cancer patients who benefit from molecular testing. The partnership is based on a model now used by Perthera and the Pancreatic Cancer Action Network (PanCan). Like PanCan, LCA will refer patients to Perthera, which offers comprehensive management of molecular profiling efforts.
"We are excited about the potential of this effort to increase access to this type of testing,” said Jennifer C. King, Ph.D., Director of Science and Research, LCA. "Now, more than ever, having detailed knowledge about the characteristics of a tumor is a critical component to determining a patient’s most effective treatment options and this program makes that a reality no matter where that patient may be.” GenomeWeb (subscription content)
Roche Wins Expanded Approval for Lung Cancer Diagnostic
Roche recently announced that FDA has approved the use of its Ventana-ALK (D5F3) assay, which helps identify ALK-positive patients who are eligible for treatment with Pfizer's Xalkori, on the Ventana BenchMark Ultra automated slide stainer.
"The FDA's approval of the Ventana-ALK CDx Assay on the Ventana BenchMark Ultra system underscores our continued commitment to expanding the identification of non-small cell lung cancer patients who may be eligible for improved treatmentCommunications | p. 22 options," said Ann Costello, Head, Roche Tissue Diagnostics. GenomeWeb (subscription content)
UNIConnect Acquired by Sunquest Information Systems
UNIConnect recently announced that it has been acquired by Sunquest Information Systems. The acquisition augments Sunquest's purchase of GeneInsight, a genetics informatics solution that streamlines the analysis, interpretation and reporting of complex genetic tests, earlier this year.
"We are both proud and excited to join Sunquest and extend our contribution in the realms of molecular laboratory automation and process management," said William S. Harten, Founder, CEO, UNIConnect. "By working together, we'll be able to deliver a complete automation solution that helps more molecular labs manage their increasingly large and complex workloads and advance the exciting realm of precision medicine." UNIConnect, Sunquest press release
UPCOMING EVENTS
The Drug Development Paradigm in Oncology: A Workshop National Academies of Sciences • December 12 - 13, 2016 • Washington, DC
Participants in the Drug Development Paradigm in Oncology workshop will discuss challenges with the traditional phased drug development paradigm in the age of targeted therapies, best practices for cancer drug development and review, lessons learned from recent expedited drug approval processes, and evidence requirements for cancer therapies before and after regulatory approval, as well as the mechanisms needed to generate this knowledge. Event website
Genetic Testing Management for Health Plans: Managing Cost, Quality and Value in a Rapidly Evolving Market NextGxDx • December 15, 2016 • Webinar
Clinical use of genetic tests is quickly becoming standard of care. As a result, spend for many health plans is rising over 25 percent per year and there are now more than 65,000 genetic testing products on the market. Health plan leaders face the overlapping challenges of establishing medical policies, contracting with laboratories, paying claims correctly and, ultimately, serving their members, all in the presence of limited data and continual change.
In this webinar, executives from UnitedHealthcare and Blue Shield of California will discuss how their organizations are addressing the challenges of managing genetic testing. Event website Communications | p. 23 2nd Personalized Medicine Conference Fusion Conferences • March 17 - 20, 2017 • Cancun, Mexico
New diagnostic technologies and therapeutic approaches are being developed and implemented that will transform patient management in the near future.
This personalized medicine conference will address:
Overviews of personalized medicine/precision medicine Precision diagnostics Cancer genomics Biomarkers Computational imaging Bioinformatics Data analytics/big data
Daryl Pritchard, Ph.D., Vice President, Science Policy, PMC, will speak at the event. Event website
If you have news or events your organization would like to share, please contact Chris Wells.
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Communications | p. 24
EDUCATION & ADVOCACY: A BLOG ON THE FIELD OF PERSONALIZED MEDICINE 2016
*** Bolded items are included after this list. ***
1. “Personalized Medicine at FDA: 2015 Progress Report” by Daryl Pritchard, Ph.D., PMC Vice President, Science Policy January 28, 2016
2. “Advancing the Dialogue: FDA’s Public Workshops on Next-Generation Sequencing Oversight” by Daryl Pritchard, Ph.D., PMC Vice President, Science Policy February 25, 2016
3. “Preparing for Inevitable? FDA’s Regulation of LDTs” by Amy M. Miller, Ph.D., PMC Executive Vice President March 3, 2016
4. “New Report: Alternative Payment Models Should Incentivize Innovation to Support Personalized Medicine” by Christopher Wells, PMC Communications Director April 18, 2016
Communications | p. 25
5. “Accessing Innovation: Why CMS Must be Actively Engaged in the ‘Moonshot’ and Precision Medicine Initiatives” by Amy M. Miller, Ph.D., PMC Executive Vice President April 19, 2016
6. “Towards Further Uptake of Pharmacogenomics: Education of Pharmacy Students and Pharmacists” Guest Blog by David F. Kisor, Pharm.D., Professor and Chair, Pharmaceutical Sciences, Director, Master of Science in Pharmacogenomics Program, Manchester University April 20, 2016
7. “Challenges and Opportunities in an Era of Personalized Medicine” Guest Blog by Stephen J. Ubl, President & CEO, PhRMA May 2, 2016
8. “The Danger in a Demo: How CMS’ Medicare Part B Proposal Could Impede Patient Access to Personalized Medicine” by Amy M. Miller, Ph.D., PMC Executive Vice President May 9, 2016
9. “Of Moonshots and Precision Medicine: Why the Time is Ripe for a National Cancer Moonshot” Guest Blog Kenna R. Mills Shaw, Ph.D., Executive Director, Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, MD Anderson Cancer Center May 19, 2016
Communications | p. 26
10. “Informed Perspectives: A Preview of the Personalized Medicine & Diagnostics Track at the 2016 BIO International Convention” by Chris Wells, PMC Communications Director May 31, 2016
11. “ICER & Personalized Medicine: Time to Engage” by Amy Miller, Ph.D., PMC Executive Vice President June 29, 2016
12. “What ICER is Missing” by Amy Miller, Ph.D., PMC Executive Vice President September 1, 2016
13. “Think the Diagnostics Community Doesn’t Agree on Anything When It Comes to LDT Regulation? Think Again.” by Amy Miller, Ph.D., PMC Executive Vice President September 20, 2016
14. “Beyond the Barriers: Deconstructing the Regulatory and Reimbursement Hurdles for Companion Diagnostics” Guest blog by Alessandra Cesano, M.D., Ph.D., Chief Medical Officer, NanoString Technologies October 3, 2016
15. “Can We Assess the Value of Personalized Medicine in Treating Cancer?” Guest blog by Dan Leonard, M.A., President, National Pharmaceutical Council October 19, 2016
Communications | p. 27
16. “It’s Time to Protect Patient Care and Rethink the Way We Define and Assess Clinical Utility in Molecular Diagnostics” Guest blog by Elaine Lyon, Ph.D., Medical Director of Genetics, Genomics and Pharmacogenomics at ARUP Laboratories, Professor of Pathology at the University of Utah School of Medicine, Co-chair of the FEND task force, Senior author of the FEND publication November 4, 2016
17. “A Chancellor’s Tale: Transforming Academic Medicine” Guest by Ralph Snyderman, M.D., James B. Duke Professor of Medicine, Chancellor Emeritus, Duke University November 8, 2016
18. “An Infrastructure for Innovation: How the 21st Century Cures Bill Established a More Favorable Landscape for Personalized Medicine in 2017” by Daryl Pritchard, Ph.D., PMC Vice President, Science Policy December 6, 2016
19. “Advancing the Promise of Personalized Medicine With Liquid Biopsies and Analysis of ctDNA” Guest blog by John Beeler, Ph.D., Vice President, Corporate and Business Development, Inivata December 8, 2016
Communications | p. 28 Of Moonshots and Precision Medicine: Why the Time is Ripe for a National Cancer Moonshot
May 19, 2016 by Kenna R. Mills Shaw, Ph.D., Executive Director, Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, MD Anderson Cancer Center
Vice President Joe Biden’s leadership of a national “cancer moonshot” is well-timed both to take advantage of and to enhance the hard-won capabilities of the nation’s cancer-fighting community.
Its proposed strategic investments in precision medicine, cancer immunotherapy, early detection, prevention, genomic analysis, data-sharing and collaboration can have a life-saving impact.
New approaches, based on decades of research, help patients now. The Wall Street Journal recently profiled the experience of a 23-year-old man struck with a particularly hard-to-treat form of acute myeloid leukemia (AML).
The story relates how genomic analysis of his leukemia led to targeted therapy that corralled his disease enough to permit a blood stem cell transplant. When his leukemia returned, his oncologists tried a series of treatments until another genomic analysis pointed to yet another targeted therapy. The result: remission, another stem cell transplant and now a year free of AML.
Such a relay race, moving from one therapy to the next to stay ahead of the disease, has been a hallmark of the treatment of advanced cancers for years. With the tools we have in hand now, we’re poised to ensure that more of these races than ever end with a victory.
How do we do better?
Communications | p. 29 A national cancer moonshot can provide pivotal support and encouragement for focused efforts underway at comprehensive cancer centers and other institutions.
For precision medicine to flourish will take a coordinated research effort to truly understand the impact of genomic and molecular variations in cancer. About 120 genes out of the 21,000 in the human genome have variations that are actionable for cancer treatment. However, we find many more variations when we analyze tumors and most of the time we don’t know what they do.
One hindrance is the common assumption that all variations in a gene do the same thing — result in activation or inactivation of a molecular pathway. Not all mutations are created equally.
For example, a clinical trial underway at MD Anderson features a drug that targets a specific fusion alteration in a gene. Other variations in that same gene don’t necessarily cause malignancy or can render even therapy targeted at the fusion ineffective.
So it’s critical to combine genomic analysis with research in functional genomics, using patient-derived xenograft animal models and cell lines, and discovery genomics. We need to combine research data with clinical data, including treatment response, and to have this not just in a subset of patients, but in all patients.
It’s critical to use our combined research and clinical information in the context of tumor evolution during treatment. We need to change the paradigm of when we test patients’ tumors so it occurs closer to when they need to switch to a new therapy than is routinely the case now.
Multiple biopsies — be they liquid gathered from circulating biomarkers or through fine-needle or core needle approaches — will be needed to guide treatment, and are generally not covered by insurers now.
When MD Anderson established its Moon Shots Program in 2012, 10 platforms were established to support our effort to accelerate the pace of converting scientific discoveries into life-saving advances in treatment, prevention and early detection.
These platforms systematically and efficiently provide expertise, technological capacity and infrastructure to the “moon shots,” multidisciplinary teams of experts that focus on 12 cancer types.
Our areas of emphasis overlap with the priorities chosen for the national cancer moonshot. We’re connecting our clinicians, basic scientists, and professional drug discovery and development teams for innovative translational research and building a powerful infrastructure to combine, share and learn from clinical and research data.
All of this is coming together in innovative clinical trials and practice-changing advances.
The time is ripe for a national cancer moonshot to accelerate the progress that is underway now in institutions across the country.
Communications | p. 30 Informed Perspectives: A Preview of the Personalized Medicine & Diagnostics Track at the 2016 BIO International Convention
May 31, 2016 by Christopher Wells, PMC Communications Director
The Biotechnology Innovation Organization (BIO) has a long history of delivering impactful educational sessions about personalized medicine, and PMC is pleased to collaborate with BIO again this year to put together a Personalized Medicine & Diagnostics Track at the BIO International Convention.
Touching on a variety of topics that include clinical care, investment and public policy reform, the three-day program promises to deliver informed perspectives on the field’s current direction:
Tuesday, June 7
Titled “30 Years of Genomics — Bridging the Past With the Future,” the opening session details how the plummeting cost of genomic sequencing is making it possible for an increasing number of health care providers to begin delivering personalized care. We no longer ask whether we can afford to sequence human genomes at scale. Instead, we have begun to examine how we will analyze incredible quantities of genomic data and what that will mean for patients.
A panel of representatives from BioNano Genomics, Domain Associates and Edico Genome will join David Barker, Ph.D., former Chief Scientific Officer of Illumina, to examine these questions during the session, which takes place from 3:30 – 4:30 p.m.
Wednesday, June 8
Communications | p. 31 Some believe widespread genomic sequencing will mean better preventive care for patients. Following introductory remarks from PMC President Edward Abrahams, Ph.D., the second day of the track will begin with an exploration of that idea during a session titled “Lifespan or Healthspan: Is it Time for a Paradigm Shift? An Interview with William N. Hait, Global Head, R & D, Janssen Pharmaceutical Companies of Johnson & Johnson.” Keith Yamamoto, Ph.D., who is the current Vice Chancellor for Science Policy and Strategy and the Vice Dean for Research in the School of Medicine at the University of California San Francisco (UCSF), will lead the discussion with Dr. Hait from 10:45 a.m. – 12:00 p.m.
But as PMC Executive Vice President Amy M. Miller, Ph.D., argues, the improved treatment and better preventive care to be discussed during that session can only be realized if public policies support personalized medicine. After lunch, she will lead a discussion with an industry expert and former Congressional staffers from both sides of the aisle regarding how recent legislative proposals may pave the way for the field. The session, called “Building Personalized Medicine Policy: The 21st Century Cures and Healthier Americans Legislative Proposals,” will take place from 1:00 – 2:00 p.m.
If successful, the kinds of public policies PMC champions will open the door to a future in which preventive care and improved treatment help lower systemic costs. Informed by that possibility, experts from JAWBONE, Johnson & Johnson, Simpatica Medicine and Sutter Health will then take another look at preventive care with a more concentrated focus on its systemic impact during a session titled “Personalized Health as a Potential Enabler of Personalized Medicine,” which will take place from 2:15 – 3:15 p.m.
Finally, informed by an understanding that industry stakeholders are invested in a personalized health care system, a panel of innovation experts from Oberland Capital, Roche, Helix, Renwick Capital, Parthenon-EY and GE Ventures will analyze which products and services in development may hold the greatest promise for advancing that kind of future during a session titled “Strategic Investment in Precision Medicine: Where to Put Your ‘Omics Dollars, NOW,” which will take place from 3:30 – 4:30 p.m.
The second day of the track will conclude with a cocktail reception co-organized with the leaders of the Digital Health Track.
Thursday, June 9
In recognition of the synergies between personalized medicine and digital health, the track’s final day will open with an important examination of the similarities between how evidence supporting both fields is evaluated. The session, titled “What Goes Around Comes Around: Applying Lessons Learned from Personalized Medicine on Evidence and Payer Coverage Requirements to Digital Health,” will take place from 9:00 – 10:15 a.m. It will draw on the perspectives of leaders from Evidation Health, GE Ventures, Quorum Consulting and UCSF to highlight the paths forward for both fields.
Wherever those paths may lead, there is widespread agreement that traversing them will require collaboration. In recognition of that opportunity, the track’s final session, titled “Companion Diagnostics: The Evolving Need for Progressive Partnerships Between Pharma and Diagnostics Companies,” will explore the value proposition for partnerships from both the pharmaceutical and diagnostic company perspectives. Senior leaders from Biodesix, Gritstone Oncology, Health Advances and Janssen Diagnostics will all take part in the discussion, which will run from 10:30 – 11:30 a.m.
Communications | p. 32 As the personalized medicine community continues to navigate toward a paradigm shift in health care, PMC looks forward to discussing these and many other topics in San Francisco.
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Communications | p. 34 ICER & Personalized Medicine: Time to Engage
June 29, 2016 by Amy M. Miller, Ph.D., PMC Executive Vice President
The Institute for Clinical and Economic Review (ICER) is a non-profit organization that uses available evidence to examine the value of therapeutics and suggest reasonable prices for them. The organization bases these judgments on a conceptual framework that combines its estimation of the clinical value of a particular drug with several other factors, including the drug’s overall budget impact.
This process may not work for personalized medicines, as became evident earlier this year when ICER examined therapies for multiple myeloma. As the Multiple Myeloma Research Foundation pointed out in their letter to ICER, “the promise of precision medicine is that each patient is unique and will consequently respond to treatment differently based on their particular genetic profile and further understanding of the biology of their disease.” This statement is particularly true for patients with non-small cell lung cancer (NSCLC).
ICER is now evaluating some targeted treatments for NSCLC, but not all of them. It is unclear how the group is considering individual variation and the diagnostic tests that determine them, which are the foundation for progress in personalized medicine and health care generally.
PMC invited the organization’s chief methodologist to address the membership. Our members appreciated that he took time to explain the assessment methodology and the process stakeholders can use to provide feedback. Because ICER plays a unique role in health policy, with health plans being the primary audience for their work, PMC will suggest improvements to ICER’s system to ensure that resulting work accounts for the challenges involved in assessing value of treatments that work for specific subgroups of patients.
Communications | p. 35 PMC then sent a letter to ICER asking for an open, inclusive and responsive public engagement process. This is more important than ever, since ICER’s evaluations have now been recognized by the Centers for Medicare and Medicaid Services (CMS) as a useful tool for evaluating how much the agency should pay for drugs as part of its Part B demonstration project, which would test new ways for CMS to pay for drugs delivered in a hospital or doctor’s office.
This summer, PMC will propose improvements to ICER’s public engagement process and methodology and comment on its draft NSCLC therapeutic evaluation once it is published in late August. We urge all PMC members to do the same.
You can find more information on ICER’s NSCLC work here: https://icer- review.org/topic/nsclc/.
Communications | p. 36 What ICER is Missing
September 1, 2016 by Amy M. Miller, Ph.D., PMC Executive Vice President
Personalized medicine challenges all aspects of health care, from the way discoveries are made to how they are regulated, covered, paid for and delivered in the clinic.
Since the mapping of the human genome 13 years ago, we have seen many efforts to alter, update and improve these processes to accommodate personalized medicines, innovative and novel diagnostic tests, and new approaches to care. Excitement is palpable throughout the world, and personalized medicine’s proponents are no longer being accused of hyping a future that does not exist.
FDA’s new drug approvals demonstrate that about one in four new drugs (28 percent) are now targeted, a ratio likely to remain the same or increase in coming years. As tech company NextGxDx’s count of genetic tests shows, there has also been an explosion of personalized medicine diagnostic tests on the market. Encouraged by the incredibly fast work of the National Institutes of Health (NIH) and FDA, U.S. policymakers in both chambers of the Republican-controlled Congress and the Democratic-controlled White House have expressed enthusiasm for the field’s potential.
Yet, some groups question the value of these advances.
Take non-small cell lung cancer (NSCLC) for example. This disease exemplifies how a personalized approach can provide more for
Communications | p. 37 patients than the standard of care. Over a few short years, several new drugs and diagnostic tests for NSCLC have come to market, changing the trajectory of treatment for the disease. The first-generation ALK-targeted drug, for example, did not cross the blood-brain barrier; the second-generation therapy does. Diagnostics for NSCLC began with one-mutation tests, moved to panel tests for multiple mutations and are now moving into the realm of next-generation sequencing tests that reveal an even more comprehensive array of valuable information about the tumor. Thanks to immuno-oncology, we now have a new class of drugs to fight the disease.
Based on discoveries in clinical medicine, FDA regularly updates labels to move drugs from the second or third line to the front-line when paired with a diagnostic test. Teams of practitioners are learning about these new tools and putting them into practice.
The Institute for Clinical and Economic Review (ICER), which has released its evaluation of two classes of NSCLC drugs, may not share my excitement about these recent advances. The organization’s value assessment process has, by design or perhaps inadvertently, no mechanism for capturing the value of targeted medicines, since its model is built on population averages.
We strongly encourage advocates for personalized medicine to engage the organization and, as a first step, suggest that ICER evolve, like so much of the health care system already has, by treating personalized medicines and companion diagnostics differently than traditional therapeutics.
Comments on ICER’s draft evidence report are due September 16, 2016.
Communications | p. 38 Think the Diagnostics Community Doesn’t Agree on Anything When It Comes to LDT Regulation? Think Again.
September 20, 2016 by Amy M. Miller, Ph.D., Executive Vice President, Personalized Medicine Coalition
As we enter a new round of discussions about laboratory- developed test (LDT) regulation, it is helpful to review where we’ve been. Many stakeholders have weighed in on the topic, and GenomeWeb’s comprehensive summary of the different proposals offers a useful comparison of them. At first glance, there appears to be little or no consensus. But listening to the community reveals more.
At the beginning of this year, I moderated a series of discussions on potential legislative solutions with representatives from the entire LDT community, including but not limited to those with an interest in personalized medicine. In short, the community agrees that a legislative solution to LDT regulation should take a risk-based approach and:
1. Protect public health labs. Public health labs should be protected by any regulatory paradigm, which means that sentinel labs must be able to develop, deploy and use rapidly developed diagnostics to address critical public health needs. 2. Allow flexibility and efficiency when managing modifications. As diagnostic device developers have long argued, the way modifications are managed by a regulatory system should be flexible and efficient to allow diagnostic tests to evolve with the clinical science that underpins them. 3. Mitigate regulatory burdens for government and industry. To reduce regulatory burdens on government and industry, regulatory agencies should, when appropriate, recognize when certain safeguards are already in place.
Communications | p. 39 These mitigation strategies can help regulatory bodies keep pace with the rapidly evolving pace of personalized medicine diagnostic testing. 4. Design a grandfathering system for tests already on the market. When FDA published its draft framework for regulating LDTs, we had no clear appreciation of the number of tests that might be captured by it. While we still do not have an exact count, tech firm NextGxDx estimates that there are nearly 70,000 personalized medicine diagnostics offered by about 300 labs with another eight to 10 coming to market each business day. To manage such an enormous workload, a regulatory agency must design a grandfathering system that will allow most tests to remain on the market unless there is a compelling reason to remove them. 5. Ensure regulatory burdens reflect testing volumes. Regulatory burden must be reflective of testing volume. For example, diagnostics designed for rare and un-met needs should be given careful and different consideration by any regulatory agency to ensure that tests are developed for micro-markets. 6. Accept valid scientific evidence for regulatory purposes — even if that evidence does not include data from a randomized control trial. Personalized medicine has challenged how health care products and services are conceived, developed, regulated, covered, paid for and used by physicians. Evidentiary requirements for regulatory review must also evolve. The community agrees that for diagnostics, valid scientific evidence should be acceptable for regulatory review, even when that evidence does not include data from randomized control trials.
Understanding these points and the logic behind them is essential to progress on this topic. Fortunately, we are not starting from scratch.
While there is no consensus about which regulatory agency should manage LDT regulation, the House Energy and Commerce Committee has released a draft legislative solution designed to address the community concerns outlined above. That proposal builds on a rich dialogue that began when the first genetic tests entered the market and continued in 2007 when Senators Ted Kennedy (D-MA) and Gordon Smith (R-OR) released a bi-partisan proposal for FDA to actively regulate lab tests. Soon after, then-Senator Obama and Senator Richard Burr (R-NC) released a draft legislative proposal that was not quite as burdensome. Finally, in 2010, Senator Hatch outlined a novel path at FDA for diagnostics, which opened up the conversation about the true difference between diagnostics and the medical devices that their regulatory structure mirrored.
These historical efforts stimulated conversation, and what was learned has influenced how we consider the topic. The Committee’s next draft will have been improved by stakeholder input, and we can expect the Senate to continue improving on the next draft.
Addressing this duel path to market and the difficulties inherent in such a regulatory paradigm is essential to the field. Once this debate is settled, we can all concentrate on the biggest issue in personalized medicine: coverage, payment and use of personalized medicine diagnostics to dramatically improve the care patients receive. Guided by these areas of agreement and rich historical dialogue, we may be able to focus on those conversations sooner than we think.
Communications | p. 40 Beyond the Barriers: Deconstructing the Regulatory and Reimbursement Hurdles for Companion Diagnostics
October 3, 2016
Guest Blog by Alessandra Cesano, M.D., Ph.D., Chief Medical Officer, NanoString Technologies
On November 16, a group of diagnostic industry representatives will convene to discuss the regulatory and reimbursement hurdles for personalized medicine diagnostics during the 12th Annual Personalized Medicine Conference at Harvard Medical School. These kinds of discussions have never been more important.
The push for personalized medicine came to the national forefront in January when President Obama announced the National Cancer Moonshot. This bold initiative aims to accelerate the discovery of personalized treatments tailored to an individual’s genetic profile and/or the tumor’s biology. Companion diagnostics (CDx) play an important role in precision medicine, as they are designed to enrich care for patients who will benefit from a “companion” drug, by helping to characterize the disease’s biology and matching it with the mechanism of action of a specific drug.
Because many of the new drugs in the pipeline work on a specific genetic or biological target that is present in some, but not all, patients with a certain kind of cancer, there is a need for an accompanying test to determine if the drug will or will not have a benefit for a specific patient. These tests may also point to which patients are at immediate risk for harmful side effects.
The promise of companion diagnostics is not under debate, but there are regulatory and reimbursement hurdles that need to be overcome before these tests achieve
Communications | p. 41 widespread acceptance and deliver on the promise. First is the cost. The development of a companion diagnostic requires a significant investment, along the lines of tens of millions of dollars. However, presently, the value that companion diagnostics bring to the health care system, specifically in terms of improving patient outcomes and effectiveness of the care delivered, is not appropriately recognized by the reimbursement system.
Supporting the development of CDx tests will require significant investment up front, but once adopted they will help the health care system realize considerable cost and time savings. Currently, the health care system favors the “one-size-fits-all” approach to drug delivery, despite the fact that the subgroup of patients benefiting from treatment is on average only 20 – 30 percent. By using CDx, we can enrich the patient population for which a specific drug is effective, resulting in better outcomes and significantly reduced costs for the health care system. Designing and executing appropriate clinical trials to demonstrate the “clinical utility” and cost-effectiveness of selection biomarkers in each particular clinical setting will be an important part of the evidence needed to obtain test reimbursement.
Another obstacle involves how CDx and personalized medicine have impacted the regulatory landscape. While the regulatory path to a CDx is relatively well defined by regulatory guidelines, a gray area remains on when/how a “generic” version of those tests (aka laboratory-developed tests or LDTs, which are analytically developed by a single laboratory without a clinical validation requirement) will be regulated by the FDA. This uncertainty has negatively affected the investor community’s appetite for diagnostic companies.
In light of these hurdles, a promising solution to driving CDx adoption is partnership among diagnostic manufacturers and the pharmaceutical industry. Biopharmaceutical companies are developing many therapies and as a result need to enroll patients in many hundreds of clinical trials. The clinical development of their drugs is going to demand enrichment strategies based on biomarkers. In fact, I can see a future in which it is the exception, rather than the rule, that drugs don’t have biomarkers when they come to market.
The biopharmaceutical industry is going to work with in vitro diagnostic companies that have the technology and the capabilities to both analyze the tumor’s biology and build an in vitro diagnostic product that can win clearance from the FDA. Ideally, these tests will be able to cut across whole drug classes (targets). Because of a limited supply of biotissue, the tests will need to be as holistic as possible. Thus, multi-plexed assays that allow for investigation of multiple aspects of biology in a single sample would be preferred.
Because of their unique ability to “match-make” a tumor’s biology with the right therapeutic choice, companion diagnostics are important for the efficient and effective treatment of patients. If the National Cancer Moonshot and other initiatives are going to be successful, there needs to be an alignment among all the stakeholders — including regulators, payers, pharmaceutical companies, physicians, patients and advocacy groups — recognizing the value of companion diagnostics in making “precision medicine” not just a promise but finally a reality.
Communications | p. 42 Can We Assess the Value of Personalized Medicine in Treating Cancer?
October 19, 2016
Guest Blog by Dan Leonard, M.A., President, National Pharmaceutical Council
Although there is a bright spotlight on the field of personalized medicine thanks to the Obama administration’s Cancer Moonshot and Precision Medicine initiatives, there are real concerns about how targeted medicines will be considered in value assessment frameworks, which are geared toward evaluating treatments for a population rather than individual patients.
This week, National Pharmaceutical Council (NPC) President Dan Leonard sat down with Amy M. Miller, Ph.D., Executive Vice President, PMC, to discuss these issues.
Dan Leonard (DL): Amy, thank you for joining me to talk about personalized medicine and value frameworks. Tell us a little about personalized medicine and its impact on patient care, especially in light of ongoing debates about costs, coverage and value.
Amy Miller (AM): Thank you for this opportunity. Personalized medicine is an evolving field in which physicians use diagnostic tests to determine which medical treatments will work best for each patient. By combining the data from those tests with an individual’s medical history, circumstances and values, health care providers can develop targeted treatment and prevention plans. This concept challenges how health care products and services are discovered, developed, regulated, covered, paid for and delivered in the clinic. Therefore, it is no surprise that personalized medicine challenges how value assessments are conducted.
Communications | p. 43 DL: The basis for personalized medicine is that every patient is unique and will respond to treatments differently, something NPC also has demonstrated in our research. How can a value assessment framework take that important concept into consideration?
AM: Fortunately for value assessment framework designers, many organizations have published suggestions for them. It is important for the value assessment questions to accurately reflect available data. Furthermore, when looking at disease areas with targeted therapeutics, value assessment frameworks must look at the full complement of clinical tools, including the diagnostic test or tests and the clinical outcome differences between a targeted and non-targeted treatment approach.
DL: The Institute for Clinical and Economic Review (ICER) is currently evaluating treatments for non-small-cell lung cancer (NSCLC), a disease that is unique to each patient and requires targeted treatment. They’ll be hosting a public meeting about that evaluation on October 20. What kinds of factors should ICER be considering as part of its review of NSCLC treatments?
AM: NSCLC is a disease where personalized medicine has transformed care over the last decade, and patients have seen tremendous improvements in morbidity, mortality and quality of life as a result. We’ve seen evolution in treatments targeting many driver mutations in the tumor. We’ve seen evolution in the types of diagnostics used to select those treatments. I think ICER needs to carefully consider all that we’ve learned over the last decade using EGFR-mutation therapeutics, value those therapeutics from a patient’s perspective, and consider how we incentivize investments in PD-1 therapeutics so we can capitalize on their tremendous potential in a similar way. PD-1 inhibitors work quite well for a subset of patients, but we do not know how best to use them yet. We will figure it out, and when we do, it will likely have tremendous implications for patients, giving them longer, better lives than comparators like chemotherapy.
DL: What have you heard from your member companies about ICER’s review of NSCLC treatments? Are there ways that ICER could better integrate those comments, as well as patient input?
AM: ICER concurrently opened a public comment period where stakeholders could suggest process changes. One example of a process change that ICER could make now is to include a more representative group of stakeholders on its advisory council. Furthermore, historically, ICER has discussed the implications of its decision after a vote on the value assessment. Simply listening to the public before voting would reassure stakeholders that ICER values their input.
DL: You had asked ICER to provide a longer comment period for NSCLC, which they granted. Do you think that was enough time? How could they improve the comment process in the future?
AM: PMC is a coalition representing pharmaceutical manufacturers, diagnostic companies, patients, providers, payers and other stakeholders, and the perspectives that these groups have together are often valuable to those who seek input on their work. However, for a coalition to engage a group like ICER requires that our members consider the issues from their perspective before joining a conversation about how to support a concept. ICER’s comment period (30 days and, in this case, including holidays) did not allow for us to engage. For a document of this magnitude and
Communications | p. 44 import, we suggested allowing for a 60 – 90 day comment period, which conforms to other organizations’ timelines. We hope ICER will consider that.
DL: These are exciting times for personalized medicine, with rapid developments in understanding this science and finding new cures. With these developments, how could — or should — ICER update its reports to remain current?
AM: In the case of NSCLC, new clinical evidence was published during ICER’s comment period, and for PD-1 inhibitors, I think we’ll see new data coming in more than once a year going forward. Because ICER is not alone in the value assessment trade, I’d suggest that the field of value assessment coordinate and come up with best practices for updating their findings. That way, innovators, patients and providers will have a timetable to engage with the update.
DL: Thanks so much for speaking with me.
For more about value framework assessments, check out NPC’s Guiding Practices for Patient-Centered Value Assessment and Current Landscape: Value Assessment Frameworks and watch the video from the organization’s conference, Assessing Value: Promise and Pitfalls.
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Communications | p. 46 It’s Time to Protect Patient Care and Rethink the Way We Define and Assess Clinical Utility in Molecular Diagnostics
November 4, 2016
Guest Blog by Elaine Lyon, Ph.D., Medical Director of Genetics, Genomics and Pharmacogenomics at ARUP Laboratories, Professor of Pathology at the University of Utah School of Medicine, Co-chair of the FEND task force, Senior author of the FEND publication
Recent advances in genomic medicine continue to provide many new opportunities to improve our modern health care system. However, before we can truly realize the full promise of precision medicine, we need a more practical and patient-centered approach for evaluating clinical usefulness for these types of molecular testing procedures. Current models for clinical utility evaluation clearly fall short of ensuring best care and usefulness for the patient, their family, their provider, and the health care system. While personalized medicine is driving health care progress today, this restricted definition of clinical utility is putting on the brakes and impeding progress.
Since the new molecular pathology Current Procedural Terminology (CPT) codes were implemented, the roles of clinical validity and clinical utility have been the subject of intense discussion. Many stakeholders have adopted very narrow definitions that do not address all the important applications, including diagnosis, prognosis, risk assessment, prediction of future disease, as well as monitoring and selection of therapies.
The ongoing shift of payer expectations from a “reasonable and necessary” to a “demonstrable clinical utility” requirement can be a difficult and unrealistic expectation for laboratories. Since the new requirement was created with therapeutic products in
Communications | p. 47 mind, applying the same standards to a test that is designed to establish a diagnosis for an inherited condition is difficult. Even if the test performs flawlessly, the patient may never be “cured” or ‘’treated;” symptoms may only be managed. In addition, many of these procedures are for diseases so rare that a statistically valid study would be almost impossible, or would at least take many years to complete. Ultimately, we need to capture evidence for the clinical utility of these procedures outside of a traditional randomized control trial setting. To achieve maximum benefit, we need to recognize that any individual test result is an intermediate outcome that relies on proper clinical interpretation and utilization in context for that specific patient.
For example, if a patient with breast cancer tests negative for specific BRCA 1/2 mutations, the physician may move forward with specific drug therapy treatment based on this information; however, the very same test may be used for someone who doesn’t have breast cancer but is being tested because there is a strong family history of breast cancer. In this case, the test is used as a screening tool before the onset of disease. It really depends on how the physician uses the information.
I currently co-chair the Association for Molecular Pathology (AMP) Framework for the Evidence Needed to Demonstrate (FEND) Clinical Utility Task Force, which was formed two years ago to address these specific challenges. The task force seeks to represent the views of the more than 2,300 AMP members, who are fully embedded in the various disciplines of molecular diagnostics, including infectious diseases, inherited conditions and oncology. AMP’s members include individuals from academic and community medical centers, government and industry, including pathologist and doctoral scientist laboratory directors, basic and translational scientists, technologists and trainees.
The FEND task force recently authored a new report published in The Journal of Molecular Diagnostics that establishes a new standard for clinical utility of molecular diagnostics for inherited diseases and cancer. One of our early goals was to have a peer-reviewed publication that could help start the next wave of discussions with all key stakeholders. In the report, we recommend a broad, patient-centered definition that takes into account the different ways that a test might be used, with an understanding that the test results may indicate follow-on activities that are not as simple as merely determining which drug to prescribe, or at what dose. Our inclusive approach utilizes a modified ACCE model and emphasizes that a clinical test result’s utility depends on the context in which it is used to classify a patient’s disease or disorder and/or guide management. We were very careful to make recommendations that can be extended to additional applications of molecular testing.
We believe our recommendations provide a reasonable and feasible path forward that puts patients and their families at the center of evaluating clinical utility for molecular testing procedures. We look forward to continued stakeholder engagement to further advance clinical genomics so that we can begin to realize the full promise of personalized medicine.
To read the full-text, free report, please visit http://dx.doi.org/10.1016/j.jmoldx.2016.05.007.
Communications | p. 48 A Chancellor’s Tale: Transforming Academic Medicine
November 8, 2016
Guest Blog by Ralph Snyderman, M.D., James B. Duke Professor of Medicine, Chancellor Emeritus, Duke University
A Chancellor’s Tale: Transforming Academic Medicine is a personal and intimate story of my 15-year journey as Duke University’s Chancellor for Health Affairs during a time of major upheaval in medicine. The story, I hope, will help demonstrate the importance of planning, leadership and organizational change to the advancement of the personalized medicine paradigm.
My experience as a scientist and a physician prior to assuming my role as chancellor did little to prepare me to deal with a highly complex and entrenched institution that, unbeknownst to itself, was in need of disruptive change. The story describes the path the institution and I took during my tenure as chancellor, during which time the Duke University Medical Center became known for innovations in medicine and the conception of personalized health care.
As CEO of the Duke University Health System, I saw that despite our delivering outstanding, state-of-the-art care, treatments were generally directed towards the reversal of episodes of late-stage disease. By 2000, anticipating the power of genomics and associated advances in technology, my colleagues and I began to envision an entirely new approach to care. Rather than being reactive to disease, health care could be proactive, predictive, preventive and personalized. As health and disease are a consequence of one’s genetics and environmental exposures over time, the availability of technologies to quantify health risks, track disease progression and identify specific disease mechanisms could be a game-changer for how care is
Communications | p. 49 delivered. Rather than starting with a disease manifestation and working back, clinicians could, in conjunction with their patient, anticipate disease risks and work to mitigate them and to treat them precisely when needed. As a consequence of this thinking, my colleagues and I conceived of an entirely new approach to health care and in doing so, laid the foundation for personalized health care.
A Chancellor’s Tale tells the story of the major transformation of Duke’s academic enterprise along with the concepts that resulted in the creation of care delivery models for personalized, proactive, patient-driven care. The book describes the difficulties of making change in a complex academic institution including what worked, what went wrong and lessons learned. My hope is that the personalized medicine community will find the stories interesting and my learning experiences useful.
The book is available for purchase at https://www.dukeupress.edu/a-chancellors-tale.
Special offer: Use coupon code E16SNYDR to save 30 percent on the hardcover edition when you order from dukeupress.edu.
Communications | p. 50 An Infrastructure for Innovation: How the 21st Century Cures Bill Could Establish a More Favorable Landscape for Personalized Medicine in 2017
December 6, 2016 by Daryl Pritchard, Ph.D., PMC Vice President, Science Policy
Barack Obama’s administration was clearly committed to the advancement of personalized medicine. In addition to launching the All of Us Research Program (formerly called the Precision Medicine Initiative) and the Cancer Moonshot effort, during his tenure President Obama regularly described personalized medicine as the future of health care.
“I want the country that eliminated polio and mapped the human genome to lead a new era of medicine, one that delivers the right treatment at the right time,” he said in his 2015 State of the Union Address.
The election of Donald Trump as the 45th President has led to a great deal of uncertainty on the future of personalized medicine and the fate of Obama’s signature personalized medicine programs.
Fortunately, Congress has confirmed its support for personalized medicine by championing the 21st Century Cures bill, which the House of Representatives passed last week by a 392 – 26 vote. The bill, designed to accelerate the pace of biomedical innovation, a goal that President-elect Trump has expressed interest in, would provide continued momentum for personalized medicine.
Communications | p. 51 “The 21st Century Cures bill supports personalized medicine,” PMC President Edward Abrahams said. “The Precision Medicine Initiative, the Cancer Moonshot and speedier access to innovative therapies based on molecular pathways, in particular, will all contribute to a healthier nation.”
Among other things, the bill:
• Authorizes $4.8 billion in funding over 10 years for programs at the National Institutes of Health (NIH) that include the All of Us Research Program and the Cancer Moonshot Research Program, as well as $500 million for FDA to implement provisions to improve innovation
• Requires FDA to make the patient experience a more central part of the drug development process
• Establishes a review pathway at FDA for biomarkers and other drug development tools
• Includes provisions related to FDA’s oversight of diagnostics, albeit without addressing the longstanding debate on the regulation of laboratory-developed tests
• Modernizes clinical trial design and evidence development as it relates to the consideration of real-world data and other topics
• Requires FDA to pilot one or more inter-center institute(s) to help develop and implement processes for coordination of activities in major disease areas between the drug, biologics and device centers
• And enhances the country’s capacity to deliver personalized medicine through improvements and incentives in health information technology.
The bill is not perfect. Policymakers have pointed out, for example, that the amount of NIH funding is half of what was proposed in the 2015 version, and that the programs are authorized rather than appropriated, thereby not guaranteeing that they will be funded. Others object to using the Affordable Care Act’s prevention funds to pay for Cures provisions. Furthermore, although proponents claim the bill’s new measures will not weaken FDA’s regulatory oversight, some critics disagree, especially regarding regenerative medicine.
But despite these concerns, the 21st Century Cures Act provides a more favorable setting for personalized medicine amid ongoing uncertainty under a new administration.
The Senate plans to consider the bill tomorrow.
The Personalized Medicine Coalition calls on Congress to pass the legislation and deliver it to the President, who has indicated his strong support for its provisions. By allocating resources for personalized medicine programs and encouraging biomedical innovation, a 21st Century Cures law could drive personalized medicine’s enormous potential for patients and the health system in a future that otherwise remains uncertain.
Communications | p. 52 Advancing the Promise of Personalized Medicine With Liquid Biopsies and Analysis of ctDNA
December 8, 2016
Guest Blog by John Beeler, Ph.D., Vice President, Corporate and Business Development, Inivata
The promise of personalized medicine gained momentum with the publication of the human genome more than 13 years ago. Enthusiasm grew over the potential to decode the genetic basis of disease and enable efficient utilization of a new generation of genomically targeted therapies. Precision medicine, whereby genomic information is integrated into clinical decision-making, intended to realize a more personalized approach and treat the right patient with the right drug at the right time.
Despite clear examples of success illustrated by the development of molecular technologies to identify genomic alterations with high specificity and sensitivity and to guide the use of targeted therapies against altered genes, including EGFR, BRAF, ALK and others, there has been a growing chorus of skeptics who infer that application of these targeted therapies to a broader population harboring respective genomic alterations is nothing more than hype. According to these skeptics, one of the primary reasons that precision oncology medicine is an illusion is the lack of data from randomized clinical trials that support the use of genomically guided therapies in more tumor diverse populations. However, there are several factors that have contributed to the paucity of data supporting advances in precision oncology medicine, particularly in patients with advanced stage disease.
The lack of tumor tissue available for molecular profiling is a primary barrier to more robust clinical data. Reasons for the lack of tissue necessary for broad molecular
Communications | p. 53 profiling include poor performance status, which precludes patients from being subjected to the invasive procedure necessary for obtaining a tissue specimen. On other occasions, it has been noted that tumors are inaccessible for a biopsy (e.g. bone metastases) and even when obtained, the limited amount of biopsy material can be insufficient for molecular profiling. According to published reports, approximately one- third of advanced stage cancer biopsies deliver tissue specimens that are either poor quality or have insufficient tumor material for a molecular analysis to be performed.
Tissue-based biopsies are further constrained by spatial and temporal limitations that may provide an inaccurate representation of the heterogeneous nature of the malignant growth, which results in the treatment of a patient based on an inaccurate molecular diagnosis. Finally, tissue biopsies are not conducive to serial sampling and are thus incapable of monitoring the molecular evolution when a tumor progresses. The failure to obtain a high-quality tissue specimen that accurately reflects the complete tumor biology may be a contributing factor to the lack of data supporting the realization of precision oncology medicine.
Fortunately, we now find ourselves at a potential inflection point, capable of positively impacting the field of personalized medicine. Recent advances in the application of “liquid biopsies” and the potential to harness molecular information in circulating cell- free tumor DNA (ctDNA) from the convenience of a simple blood draw offers a “game- changer.” Analysis of ctDNA represents a new generation of molecular applications that are capable of producing data that was previously unavailable, thereby helping to deliver on the full promise of providing health care that is both more precise and personal.
First identified more than 60 years ago by Mandal and Metais, advances in genomics and molecular methods now allow analysis of cell free DNA with unprecedented sensitivity and specificity to expand the range of opportunities for liquid biopsy applications that will impact the major aspects of a patient’s care. Analysis of ctDNA can identify genetic alterations that enable therapy selection, quantitatively monitor treatment progress, including disease recurrence via serial sampling, and detect new resistance mutations as they emerge. This liquid biopsy approach has the potential to revolutionize cancer care and improve and/or resolve many of the limitations inherent in current tissue-based standard treatment protocols for providing a broad molecular profile.
This is particularly relevant in non-small cell lung cancer (NSCLC), where a significant number of patients with advanced NSCLC are not receiving molecular testing for first- line therapy and even less are receiving a molecular profile at disease progression following first-line therapy. The opportunity to improve the availability of a molecular profile when one is not otherwise obtainable and provide valuable molecular information that impacts clinical decision-making offers to help deliver on the promise of personalized medicine.
In contrast to the current state of euphoria generated by the liquid biopsy approach and analysis of ctDNA, there is still significant work to be done to generate data illustrating the benefits of ctDNA. The data is necessary to address the limitations of current tissue-based testing, to drive adoption and utilization of this innovative approach, and to improve trust in the regulatory and reimbursement landscape. At Inivata we believe it is vital to get this aspect correct, most importantly for cancer patients, to fulfill the promise of personalized medicine.
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PMC SPEAKING ENGAGEMENTS 2016
Note: Hosting PMC members are indicated in parentheses.
1. 2nd Annual Biosimilars Summit February 8 – 9, 2016 Berlin, Germany
2. Novartis Precision Oncology Advisory Board Meeting (Novartis) February 18 – 19, 2016 Fort Lauderdale, Florida
3. Cancer Center Business Summit (Foley & Lardner) February 24 – 25, 2016 Phoenix, Arizona
4. ACLA Annual Meeting (ACLA) March 3, 2016 Washington, District of Columbia
5. Molecular Medicine Tri-Conference (CHI) March 7 – 9, 2016 San Francisco, California
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6. PhRMA Annual Meeting (PhRMA) March 7 – 9, 2016 Washington, District of Columbia
7. Business of Biotech Conference (Moffitt Cancer Center) March 18, 2016 Tampa, Florida
8. +Dx Diagnostics Forum (McDermott + Consulting) April 5, 2016 Washington, District of Columbia
9. Oracle Industry Connect (Oracle) April 12 – 13, 2016 Orlando, Florida
10. World Medical Innovation Forum: Cancer (Partners Healthcare) April 25, 2016 Boston, Massachusetts
11. Genomic Analysis Symposium (Takeda) May 1 – 3, 2016 Boston, Massachusetts
12. Big Data Symposium May 5, 2016 Washington, District of Columbia
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13. 2016 BIO International Convention (BIO) June 6 – 9, 2016 San Francisco, CA
14. International Congress on Personalized Health Care June 12 – 15, 2016 Montreal, Canada
15. Precision Medicine Leaders Summit (The Journal of Precision Medicine) August 10 – 12, 2016 San Diego, CA
16. House of Pharma and Healthcare Annual Meeting September 12 – 13, 2016 Frankfurt, Germany
17. International Molecular Diagnostics Congress September 14 – 15, 2016 Barcelona, Spain
18. United Nations’ Roundtable on Personalized Medicine September 23, 2016 New York, NY
19. National Association of Specialty Pharmacy Annual Meeting September 28, 2016 Washington, DC
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20. Economist’s War on Cancer September 28, 2016 Boston, MA
21. Forum on Healthcare Innovation (Jackson Laboratory) October 26 – 27, 2016 Farmington, CT
22. Innovate Conference (INOVA) October 28, 2016 Falls Church, VA
23. 3rd Annual Big Data in Precision Medicine Summit November 1 – 2, 2016 Washington, DC
24. 13th Annual Personalized Medicine Conference November 15 – 17, 2016 Boston, MA
25. Roche Media Event: Transforming Cancer Care with Molecular Information (Roche) November 18, 2016 Boston, MA
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STAFF PUBLICATIONS 2016
*** Bolded items are included as clips in the 2016 Impact Report. ***
1. “Foreword” in The Precision Oncology Annual Trend Report: Perspectives From Payers, Oncologists and Pathologists (2nd ed.) January 2016
2. “Personalized Medicine at FDA: 2015 Progress Report” in The Journal of Precision Medicine January/February 2016
3. “Personalizing the Future of Cancer Care” distributed by Mediaplanet as insert in USA Today February 2016
4. “What Contributes Most to High Health Care Costs? Health Care Spending in High Resource Patients” in Journal of Managed Care & Specialty Pharmacy February 2016
5. “Personalized Medicine at FDA: 2015 Progress Report” in Personalized Medicine in Oncology February 2016
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6. “Powering Our Progress Against Cancer” in The Hill February 2, 2016
7. “Regulation and Reimbursement Policies Will Determine the PMI’s Legacy” in Personalized Medicine in Oncology March 2016
8. “Personalized Medicine’s Skeptics” in Personalized Medicine in Oncology April 2016
9. “Towards Targeted Therapeutics: The Pharmaceutical Industry and Personalized Medicine” in The Journal of Precision Medicine April/May 2016
10. “The Impact of Alternative Payment Models on Oncology Innovation and Patient Care” in Clinical Cancer Research April 2016
11. “Biden’s Moonshot” in Personalized Medicine in Oncology May 2016
12. “Patient and Provider Readiness for Personalized Medicine” in Personalized Medicine in Oncology May 2016
13. “The President and Personalized Medicine” in Personalized Medicine in Oncology August 2016
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14. “PMC’s Progress Report” in Personalized Medicine in Oncology October 2016
15. “Liquid Biopsies, A New Tool for Personalized Medicine” distributed by Mediaplanet as insert in USA Today October 2016
16. “The Cancer Moonshot: It’s Time to Engage Patients” in Morning Consult November 2016
17. “Where We Agree When It Comes to Regulating Laboratory-Developed Diagnostics” in Personalized Medicine in Oncology November 2016
18. “Precision Oncology is Not an Illusion” in Nature November 2016
19. “An Infrastructure for Innovation: How the 21st Century Cures Act Establishes a More Favorable Landscape for Personalized Medicine in 2017” in Personalized Medicine in Oncology (in press)
20. “Strategies for Integrating Personalized Medicine into Health Care Practice” in Personalized Medicine (in press)
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EARNED MEDIA 2016
*** Bolded items are included as clips in the 2016 Impact Report. ***
1. “FDA Approved” in GenomeWeb January 2016
2. Nine Tips for Success in Precision Medicine: Concise Guidance for Biopharma and Diagnostic Developers (white paper from Health Decisions) January 2016
3. Many Novel Drugs Approved by FDA in 2015 are Personalized Medicines” in Pharmaceutical Processing January 2016
4. “Interview: Amy Miller, Executive Vice President, Personalized Medicine Coalition” in Pharmafocus January 2016
5. “2015: A Banner Year for Personalized Medicine” in The Catalyst January 2016
6. “2015: A Banner Year for Personalized Medicine” in NovaMedica January 2016
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7. “Edward Abrahams: ‘La medicina personalitzada redueix costos sanitaris’” in Societat (Spain) January 2016
8. “Whether ‘Precision’ or ‘Personalized,’ More New Drugs Need Companion Diagnostics” in Pharmaceutical Commerce January 2016
9. “Calls Intensify to Get Medicare to Pay for Genetic Sequencing of Tumors” in STAT News January 2016
10. “Coverage Urged” in GenomeWeb January 2016
11. “FDA Medical Sprint Accurate? 15 New Drugs Approved Personalized Medicine, 28 Percent” in Sohu Health (translated from Chinese) January 2016
12. “Accelerating Progress Against Cancer Requires Collaboration, Research” published by The Henry J. Kaiser Family Foundation February 2016
13. “RBCC: Drug Approvals Show Personalized Medicine Gaining Favor With Feds and Public” in BusinessWire February 2016
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14. “FDA to Finalize LDT Guidance Amid Uncertainty on Number of Genetic Tests Impacted” in GenomeWeb January 2016
15. “E&C Required Pledge of Support for Entry into LDT Stakeholder Meeting” in InsideHealthPolicy February 2016
16. “Stakeholders Again Seek Consensus on LDTs as Congress Weighs Options” in InsideHealthPolicy February 2016
17. “Over 1 in 4 New Drugs Approved by FDA in 2015 are Personalized Medicines” in Thepharmaletter February 2016
18. “Next-Generation Sequencing Oversight” in ClinicalOmics February 2016
19. “Personalized Medicine Approvals Experience Sharp Increase” in Managed Healthcare Executive February 2016
20. “FDA Reform Focus of Senate’s 2nd Cures Markup” in Bloomberg BNA February 2016
21. “At Workshop, FDA Gathers Input on How to Regulate NGS Panels to Guide Cancer Treatment” in GenomeWeb February 2016
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22. “Precision Medicine, Part Three: Cost and Time No Longer Barriers to Sequencing” in Individualized Medicine Community February 2016
23. “Next-Gen Gene Sequencing Tests Need Standards But Not Too Many, Workshop Told” in Bloomberg BNA March 2016
24. “Maximising Discovery Success” in Manufacturing Chemist March 2016
25. “Putting It Out There” in GenomeWeb March 2016
26. “Genetic Test Firm to Make Customers’ Data Publicly Available” in The New York Times March 2016
27. “Bloomberg Advantage: Miller on Personalized Medicine Benefits” in Bloomberg Advantage March 2016
28. “Sen. Alexander Introduces Bill to Continue Implementation of Precision Medicine Initiative” in GenomeWeb March 2016
29. “What is Personalized Medicine?” in Boston Commons High Tech Network March 2016
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30. “The FDA, Your Doctor and Direct-to-Consumer Genetic Testing Companies: Who Should Decide How Your Genetic Data is Gathered, Shared and Interpreted?” in Science & Technology in Public Policy at Boston University March 2016
31. “Will ‘Open Source’ be the Future of Genetic Diagnostics?” in JD Supra Business Advisor March 2016
32. “Are You Ready for the 2016’s Pharma and Biotech USA Industry?” in PRSync March 2016
33. “State Lab Overseer NYSDOH Issues Plan for LDT Pre-Market Approval” in GenomeWeb March 2016
34. “Warren, Enzi Bill Seeks to Tighten Protections for Genetic Information in Research” in GenomeWeb April 2016
35. “Lab Group Urges FDA to Wait for Congress on LDT Issue” in The Gray Sheet April 2016
36. “What Is Personalized Medicine?” in Uranium Investing News April 2016
37. “Eric Dishman Selected as Director of Precision Medicine Initiative Cohort Program: PMC Commends NIH” in Leaders in Pharmaceutical Business Intelligence Group April 2016
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38. “Precision Medicine Helped Him Beat Cancer. Now He’s Leading Obama’s Initiative” in STAT News April 2016
39. “Intel Exec Brings Tech, Personal Experience to Precision Medicine Initiative Job, Say Colleagues” in GenomeWeb April 2016
40. “Report Identifies Considerations for Alternative Payment Models for Cancer Care” published by American Association for Cancer Research April 2016
41. “Precision Medicine: Intel Corp. Executive to Lead NIH Precision Medicine Study” in Bloomberg BNA April 2016
42. “Pharma, Policymakers Join Stakeholders to Discuss Alternative Payment Models in Cancer Care” in First Report Managed Care April 2016
43. “Personalized Medicine — Great Potential, But Questions to be Answered” in Diginomica April 2016
44. “What Changes are in Store for Pharmaceutical Manufacturers?” published by European Pharmaceutical Manufacturer April 2016
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45. “The Promise of Precision Medicine” in Applied Clinical Trials April 2016
46. “NIH Taps Intel Executive Eric Dishman to Head PMI Million Patient Cohort” in FDA Week April 2016
47. “Vitals” in Inside CMS April 2016
48. “Proove Biosciences Appoints John Steiner to Board of Directors” in PRWeb May 2016
49. “Obama Plan to Overhaul Medicare Part B is Unlikely to Get Derailed” in STAT News May 2016
50. “MatchMiner Wins Harvard Business School/Kraft Precision Trials Challenge” in PR Newswire May 2016
51. “Briefing: The Personalized Medicine Coalition” in AP Alert May 2016
52. “Microcephaly Risk of Zika in First Trimester Could be as High as 13 Percent” in Politico May 2016
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53. “Former AdvaMed CEO Says Diagnostics Are an Underappreciated Part of Medicine” in Medical Device Daily May 2016
54. “PhRMA: Medicare Rx Demo Bad for Personalized Medicine” in Bloomberg BNA May 2016
55. “New PhRMA CEO: Dx an Underappreciated Part of Medicine” in BioWorld Today May 2016
56. “Opioid Treatment Caps Surface as Top Priority” in Politico May 2016
57. “Applications of Nucleic Acid Testing in Diagnosis and Therapy” in Medical Laboratory Observer June 2016
58. “Hillary Clinton vs. Donald Trump on Medical Research” in STAT News June 2016
59. “Precision Lung Cancer Drugs on Pricing Evaluation Group’s Agenda” in GenomeWeb June 2016
60. “What’s Driving Personalized Medicine: Genentech Explains Some of the Trends and Driving Factors of Personalized Medicine” in Pharmaceutical Processing July 2016
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61. “PhRMA CEO Hails Progress in Targeted Therapies, Decries Regulations” in Oncology Times July 2016
62. “For Lab Industry, FDA Draft Guidance on NGS Testing Inseparable From Larger LDT Debate” in GenomeWeb July 2016
63. “Dems Cave on CARA Funding” in Politico July 2016
64. “Genomics Doctors Agree on the Need for HCP Education” in DigVid360 July 2016
65. “Which Emerging Trends in Healthcare Will Impact Medical Librarians the Most Over the Next 10 Years?” published by Elsevier July 2016
66. “FDA Releases Draft Guidance Outlining Principles of Drug/Diagnostics Codevelopment” in GenomeWeb July 2016
67. “FDA Offers New Draft Guidance on How to Co-Develop IVDs, Therapeutics” in Regulatory Focus July 2016
68. “10 Reasons Why People Should Not Fear Digital Health Technologies” published by medicalfuturist.com July 2016
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69. “Other Side of the Coin for Personalised Medicine and Healthcare: Content Analysis of ‘Personalized’ Practices in the Literature” in BMJ Open July 2016
70. “FDA Issues Draft Guidance for Codevelopment of IVD and Therapeutic Products” in Med Device Online July 2016
71. “Illumina, Genentech and BIO Weigh in on FDA Draft Guidance on Companion Diagnostics” in Regulatory Focus July 2016
72. “20 Medical Technology Advances: Medicine in the Future Part II” published by medicalfuturist.com July 2016
73. “International Molecular Diagnostics Congress 2016” published by Bio-Equip August 2016
74. “Nonprofit Seeks to Dispell ‘Myths’ About Its Work” in STAT News August 2016
75. “31 Health IT & Revenue Cycle Wiz Kids” in Becker’s Hospital Review August 2016
76. “Profile of Director Nancy A. Simonian, M.D., of Seattle Genetics” in Plus Company Updates August 2016
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77. Profile of Michael Pellini, M.D., Chief Executive Officer of Foundation Medicine” in Plus Company Updates August 2016
78. “Profile of Kimberly Popovits, Chairman of the Board, Chief Executive Officer & President of Genomic Health, Inc.” in Plus Company Updates September 2016
79. “Nutrigenomics — The Next Generation Nutraceuticals” in Natural Products INSIDER September 2016
80. “ICER Puts Hard-Fought Progress in Non-Small Cell Lung Cancer Treatment at Risk” in Publicnow September 2016
81. “Moonshot Panel Issues Proposals; Says Funding, Data Sharing, Reimbursement Key” in InsideHealthPolicy September 2016
82. “Cancer Advocacy Groups Praise Moonshot Panel’s Recommendations” in Morning Consult September 2016
83. “Cancer Moonshot Recommendations Highlight Precision Medicine, Data Sharing, Genetic Screening” in GenomeWeb September 2016
84. “Cancer Moonshot Scientific Agenda Released” in Bloomberg BNA September 2016
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85. “Moonshot Panel Issues Proposals; Says Funding, Data Sharing Key” in FDA Week September 2016
86. “ICER: TKIs, PD-1 Agents Yield ‘Uncertain’ Clinical, Financial Benefit for NSCLC” in HemOnctoday September 2016
87. “Funding Key to Getting Human Cell, Tissue Products to Market” in Bloomberg BNA September 2016
88. “New Precision Medicine Alliance Targets Community Healthcare Providers” in GenomeWeb September 2016
89. “Dignity Health and Catholic Health Initiatives Team Up to Launch the Largest Community-Based Precision Medicine Program in the U.S.” in 4-Traders September 2016
90. “Dignity Health, Catholic Health Initiatives Collaborating on Precision Medicine Program” in Healthcare Informatics September 2016
91. “Use of Technology to Learn About Healthcare Rises in US Despite Confusion Over Health Plan” in Healthcare Risk Management Review September 2016
92. “The Economist Presents: ‘The War on Cancer: Scaling Progress’” published by Close-Up Media September 2016
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93. “Dignity Health Joins Forces With Catholic Health Initiatives” in Manufacturing Close- Up September 2016
94. “Dignity Health Links With Catholic Health Initiatives” in Professional Services Close- Up September 2016
95. “New Precision Medicine Alliance Will Bring More Personalized Medicine Closer to 12 Million Patients” in The Journal of Precision Medicine September 2016
96. “Main Basse Sur La Medicine de Demain” in L’Expansion (France) October 2016
97. “Pharmacogenomics: How Genetic Testing is Making Therapeutics Safer and More Effective” in Medical Laboratory Observer October 2016
98. “‘Uncertain’ Benefits for TKIs and PD-1 Agents in NSCLC” in Medscape October 2016
99. “A Woman Who Was Given Three Years to Live in 1996 Explains How Her ‘Death Sentence’ Made Her One of the World’s Best Leaders” in Business Insider October 2016
100. “Critics Say Cancer Moonshot Goals Lack Funding” in Politico October 2016
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101. “The Promise of Precision Medicine” published by 3D Perspectives October 2016
102. “FDA Companion Diagnostic Road Map Critical Tool, Clarity Sought” in Bloomberg BNA October 2016
103. “Obama’s Precision Medicine Initiative: An Update” in Managed Healthcare Executive October 2016
104. “Profile of Stephen L. Eck, M.D., Ph.D., Strategy & Development Committee of Luminex Corporation” in Plus Company Updates November 2016
105. “Stakeholders: Codevelopment Guide Lacks Clarity on Complementary Dx” in FDA Week November 2016
106. “Cures Roundtable Participant: Patients Need to Be Congress’ Top Priority as They Finish Their Work in 2016” in States News Service November 2016
107. “Genomics: Heralding a New Diagnostics Era” in Healthcare Dive November 2016
108. “FDA Holding Off on Finalizing Regulatory Guidance for Lab-Developed Tests” in GenomeWeb November 2016
Communications | p. 78
109. “FDA Regulator Defends Decision to OK Sarepta Drug” in The Boston Globe November 2016
110. “Fokus auf Gene Statt Organe” in derStandard (Austria) November 2016
111. “Personalisierte Medizin - Genetik-basierte Heilkunde auf Vormarsch” in Science APA (Austria) November 2016
112. “SWHR Names Amy Miller, Ph.D., New Chief Executive Officer” in PRWeb November 2016
113. “Wieso ein US-Experte ‘echte Hoffnung’” in Kurier (Austria) November 2016
114. “Precision Medicine Has Bipartisan Support, Proponents Assure Amid Trump Administration Transition” in GenomeWeb November 2016
115. “Cures Heading Toward Big Vote in the House” in Politico November 2016
116. “Duck Creek Technologies Names Chief Revenue Officer” in One Page News November 2016
117. “Gibt es Bald Die Personalisierte Krebstherapie?” in Die Presse (Germany) November 2016
Communications | p. 79
118. “People in the News” in GenomeWeb December 2016
119. “Navigator Hires Transition’s Keiser, Commerce Committee’s Orlando to BakerHostetler” in Politico December 2016
120. “Consumer Genomics Policy Forum Sponsored by 23andMe” published by 23andMe December 2016
Communications | p. 80 Click here to download. PERSONALIZED MEDICINE IN BRIEF
VOL. 7, FALL 2016 Developments in Brief
2016 JULY 15 FDA Releases Draft Guidance on Codevelopment MARCH 8 of Drugs and Diagnostics Centers for Medicare and Medicaid Services Proposes PAGE 18 to Test New Model for Paying for Personalized Medicines Reimbursed Under Medicare Part B AUGUST 5 PAGE 18 Immunotherapy Trial Results Billed as Win for Personalized Medicine MAY 20 PAGE 08 MatchMiner Wins Harvard Business School Kraft Precision Medicine Accelerator’s Precision Trials AUGUST 10 Challenge PMC’s Health Care Working Group Identifies 39 PAGE 12 Strategies for Integrating Personalized Medicine into Health Care JULY 6 PAGE 10 Obama Administration Advances Precision Medicine Initiative With Research Funding and Draft Guidance AUGUST 19 on Next-Generation Sequencing The Institute for Clinical and Economic Review PAGE 06 Releases Draft Evidence Report on Non-Small Cell Lung Cancer PAGE 04 Click here to download. CONFERENCE PROGRAM November 15–17, 2016
JOSEPH B. MARTIN CONFERENCE CENTER • HARVARD MEDICAL SCHOOL 77 AVENUE LOUIS PASTEUR, BOSTON, MA 02115