GLOBAL

FORUM | ISSUE 5 ƫĂĀāāƫđƫ ƫăƫ

10 Best Practices

22 Special Section: Comparative Effectiveness

100 Patient Fellowship Program

IN EACH ISSUE President’s Message | 3 Regulatory Updates | 92

GFCovers and Spines.oct.indd 1 9/20/11 3:10 PM 0197V01GlobalForumAd212x277:Layout 1 27/4/11 22:28 Page 1

Reducing the Cost and Complexity of Safety & Risk Management

Need more good reasons to switch to a hosted Total Safety™ solution?

ARIS GLOBAL understands that by reducing the cost and Agrowing list of life complexity of safety, you can focus on what you do best. science companies and CROs, from small to large, agOnDemand™ eliminates the need to invest in new hardware, have chosen agOnDemand. software or support staff by giving you a ready-to-use solution on Request the agOnDemand a subscription basis. white paper. Fast deployment—typically in a matter of a few weeks—lets you easily ensure compliance and manage risk. 24x7 availability and end- Visit www.arisglobal.com/WP_agOD to-end support give you total peace of mind.

Visit Booth #415 at the DIA 47th Annual Meeting

GFCovers and Spines.oct.indd 2 9/20/11 3:10 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

Medicines’ Effectiveness, Role of a Patient, and Innovations

ithin a rather short space of time (see our April 2010 W Global Forum), we have come back to the important topic of the real value of medicines. The question if a new Global Forum Editorial Board drug is better than any of those already available on the market has been gaining importance over time. Attempts to Andrzej Czarnecki, MD, PhD, DSc scrutinize the add-on benefit of a drug are Editor-in-Chief EDITOR-IN-CHIEF already in place, be it on national level (e.g., UK, Australia, Canada) or a local level (e.g., Richard Chamberlain, PhD hospital formularies). Therapeutic value is ECS, Inc. a very fair question; specifically for the Ronald D. Fitzmartin, PhD, MBA individual patient that wants to be healthy Managing Partner again, and even more so if he or she has Decision Analytics, LLC already been treated with other available drugs, with limited or no success. Alberto Grignolo, PhD PAREXEL From the provider’s perspective, everyone is aware that there were never Betty R. Kuhnert, PhD, MBA unlimited funds to cover treatment PharmaNet costs. Therefore, it seems that debating comparative effectiveness research (CER) Sarah Powell and putting existing and developing new Thomson Reuters methodologies into practice for assessment of the therapeutic and cost value of Nancy D. Smith, PhD Potomac, MD ANDRZEJ CZARNECKI ANDRZEJ CZARNECKI treatments to support decision-making is the right thing to do. Jean H. Soul-Lawton, DPhil GlaxoSmithKline CER should be distinguished from cost effectiveness. It is important therefore to J. Rick Turner, PhD factor in two other aspects of the issue Quintiles OPEN FORUM that should not be forgotten in the drive towards increased effectiveness in the Qingshan Zheng, PhD environment of limited resources – the Shanghai University of individual patient and the public health. Chinese Medicine, China Any practicing physician knows from experience that patients respond differently to different drugs, including those

1

OF-Open Forum.indd 1 9/19/11 11:04 AM from the same pharmacological individual patient. The overall also raise concerns that innovation class. Comparative effectiveness impact of drug costs in a health in medicine can be affected. If is assessed on larger groups of budget is large, but not as substantial this were the case, careful thought patients (public health perspective), as we frequently are persuaded to ought to be given to such a potential sometimes larger than the one think. More specifically, drug costs impact. in which efficacy and safety has account for about 10% of health been established in pivotal clinical care spending, so a substantial These and related points are the trials. We may, therefore, face two 10% savings on drug costs would focus topic of this issue. We also concepts that are not necessarily amount to only a 1% saving in present further developments in aligned – a lack of superiority spending on the health care budget. health technology assessment/ of a tested treatment but, at the Despite the size of these budgets, CER and some practical aspects same time, a proven efficacy in the one cannot regard the 1% overall of methodologies used for these tested indication. Such treatment saving as great on a percentage basis studies. With a growing interest in should, without any doubt, find its unless it is truly justified. Looking the area, additionally stimulated by way to an individual patient as an from this perspective, therefore, substantial federal funds allocated alternative, as personalized care it is effectiveness and not cost by the US government, it is worth a is one of the outcomes of CER. effectiveness that should drive the closer look at these developments. Subsequently, if the product is CER studies. clearly inferior to others being used, In the “Best Practices” section, both the physician and the patient We should do all the necessary work there are several interesting articles; will recognize its true value and the to establish “real life” effectiveness, however, I would like to draw market will “regulate” itself. The and not concentrate excessively on special attention to the information landscape of current approaches to the cost outcomes of CER that may provided by “Nanotechnology, medicines is briefly set out in one achieve a relatively small overall Nanomedicine, Implications for of our articles (“CER: International cut in spending. This is not to say Drug Safety, Pharmacovigilance Developments and Impact”) when that CER and the understanding and Risk Management.” We do not comparing definitions of Evidence- of the cost should not be a top frequently get the opportunity to based Medicine, CER and Patients- priority. By all means, physicians learn something different about centered Outcomes Research. and patients have a great interest a topic that is perceived as an in knowing which of the available important step to the future. I would Increasing populations and products delivers the best health like to extend my thanks to Dr. budgetary constraints pave the way value for them and allows for savings Sougato Das for serving as section for the development of CER, which that should ultimately translate chair for this special topic and his should serve public health purposes into better health service overall. excellent work on the CER section of well. But, it should also serve the Implementing CER/HTA widely may this issue. ■ OPEN FORUM

2 GLOBAL FORUM OCTOBER 2011

OF-Open Forum.indd 2 9/19/11 11:04 AM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

CER & HTA: NEW DAYS FOR DIA

his issue presents a special focus on CER/HTA related initiatives from an on the issue of Comparative international array of pertinent organizations, T Effectiveness Research and Health such as Health Technology Assessments TechnologyTechnolo Assessment. International (HTAI), the European Federation of Pharmaceutical Industries & Associations Current discussion around CER, as it is known (EFPIA), the National Institute for Health & in the US, and HTA, its European counterpart, Clinical Excellence (NICE, UK), ARCS Australia can sometimes bring to mind George Bernard Ltd. (previously the Australian Association Shaw’s famous quote that, “England and of Regulatory and Clinical Scientists), the America are two countries separated by a International Society for Pharmacoepidemioloy common language.” CER and HTA employ (ISPE), the US FDA, and others. different terms, but their concepts are very similar and their goals are close: To identify and These conversations illustrate how DIA can evaluate objective evidence to determine the be a key player, because these conversations optimum health care treatment options, at both are precisely what DIA does best: Create the patient and population levels, at the best opportunities for stakeholders from the YVES JUILLET cost. Increasingly, regulatory approval no longer different sides of an issue – in this case, means simultaneous, instant market assess; patients, researchers, clinicians, regulators, CER and HTA assessments are becoming new payers, and legislators – to share their gatekeepers responsible for recommendations knowledge, clarify concepts, and facilitate that public and/or private payers fund the cost common terminology, for us to take back and of new health technologies after regulatory use in our respective workplaces to benefit approval. the world’s health. We specifically identified the need for more collaboration between the At the EuroMeeting in Geneva this past March, different groups engaged in this activity, and and the DIA 2011 Annual Meeting in Chicago to facilitate the bridge between the regulatory this past June, DIA convened two special and the HTA perspectives, particularly at two executive consultation forums on CER/HTA. specific points in the life of a product. Discussions at these forums centered on the

concepts of CER and HTA in both regions, The first point is during product development. PRESIDENT’S MESSAGE their practical implications on drug and device In the US, the applicant and Agency interact development, and, just as importantly, where during the IND/NDA process; in Europe, and how DIA can advance these discussions the applicant and Agency interact through from theoretical scenarios to practical actions voluntary Scientific Advice meetings. This early and operations for the various stakeholders and stage in both processes is also an opportunity our members. Participants in these discussions to initiate contact, not only with the pertinent represented the entire spectrum of stakeholder regulatory authority but, simultaneously or in perspectives, including regulatory, industry, parallel, with the responsible CER/HTA bodies. patient groups, academia, and HTA agencies. The second point arises during initiation of the post-marketing pharmacovigilance studies The DIA 2011 CER/HTA consultation forum designed to verify the product’s safety profile, in Chicago was informed by presentations which can also introduce CER/HTA parameters 3

PM-President's Message.indd 3 9/19/11 11:23 AM to identify and analyze how the product performs in real- subtitled, Cross-Functional Working for Better Results world use. for it will address the technical aspects of eClinical, risk management, post-approval studies, and related Training in these new approaches must also be considered regulatory issues. Dr. Juan Carlos Groppa, Congress as a priority. Fortunately, we have seen DIA successfully Chair and Past President of the Argentine Society of build and equip our stakeholders to cross such bridges Pharmaceutical Medicine (SAMEFA), from our host before. One of the best and most recent examples is nation, will introduce DIA’s 8th Latin American Congress the EudraVigilance training program. One of the main of Clinical Research. Personally, just a few days prior (but pillars of risk management and pharmacovigilance half a world away), I will have the privilege of welcoming in the European Union (EU), EudraVigilance is the attendees to DIA’s 6th Annual Conference on Drug European data-processing network and management Discovery & Clinical Development in Mumbai, India and system established at the European Medicines Agency to DIA’s 8th Japan Annual Meeting that will be presented (EMA) to support the electronic exchange, management, in Tokyo soon thereafter. More specific to this Global and scientific evaluation of safety reports related to all Forum issue, DIA will present our Making Evidence medicinal products authorized in the EU. DIA has served Matter in the Marketplace: Applying Comparative to organize EudraVigilance training courses for the EMA Effectiveness to Health Technology Assessments in Real- since this electronic reporting became mandatory in World Settings in Washington, DC, the US capital, in early 2005, and has since trained literally hundreds of users November. throughout Europe with the skills they need to effectively utilize this network. Please accept my invitation, on behalf of all our members, volunteers, and other contributors, to discover more For this fall, the volunteer program committees and about CER/HTA in this Global Forum as well as the other leadership have been preparing several major benefits presented by these and other DIA educational opportunities for you, thanks to large meetings all opportunities. These exemplify how DIA can contribute over the world. In October, DIA Europe will present benefits to our members and to all stakeholders our comprehensive 5th Annual Clinical Forum: Basel collaborating and participating in the activities that these 2011, which is most appropriately and illustratively opportunities are developed to address. ■ PRESIDENT’S MESSAGE

4 GLOBAL FORUM OCTOBER 2011

PM-President's Message.indd 4 9/19/11 11:23 AM PM-President's Message.indd 5 9/19/11 11:23 AM GLOBAL FORUM OCTOBR 2011, VOL 3 ISSUE 5

Publishing Information CONTENTS Paul Pomerantz, Executive Director Global Forum Staff Andrzej Czarnecki, MD, PhD, DSc, Editor-in-Chief Lisa Zoks, Editor Judy Connors, Publications Manager Chris Slawecki, Senior Copywriter Joe Krasowski, Marketing Communications Manager Freelance Writers 64 Pat Friia, Joyce Litwin Zimmerman Mission The Global Forum provides a multidisciplinary, neutral forum OPEN FORUM for communicating information related to drug development 1 Medicines’ Effectiveness, Role of a Patient, and and lifecycle management on a global basis. The Global Forum Innovations disseminates content that is relevant to members’ professional Andrzej Czarnecki experiences, including international industry and regulatory updates and news of the association and its programs. The magazine is circulated six times a year as a benefit of PRESIDENT’S MESSAGE DIA membership. 3 CER & HTA: New Days for DIA Publishing, Subscription, and Advertising Offices: Yves Juillet Drug Information Association (DIA), 800 Enterprise Road Suite 200, Horsham, PA 19044-3595, USA. EXECUTIVE DIRECTOR’S MESSAGE Contact Information 8 DIA, CER & HTA: New Rules for a New Game Worldwide Advertising Sales, Michael Boucher 267 419 8735 Subscription Information, Customer Service 215 442 6100 Paul Pomerantz Membership Services, Mike McGovern 215 442 6129 Senior Marketing Manager, Mike Keller 215 442 6173

The Global Forum (ISSN: 1944-1991) is a publication of the BEST PRACTICES Drug Information Association. Editorial Office: Drug Information 10 Are Source Code Escrow Accounts Still Needed? Association (DIA), 800 Enterprise Road, Suite 200, Horsham, Harry Huss, Randall Basinger, Richard Chamberlain, PA 19044-3595, USA; phone: 215 442 6100; fax: 215 442 Jim McCormack, Richie Siconolfi 6199. Copyright © 2011, Drug Information Association. 13 Nanotechnology and Nanomedicine The Global Forum (ISSN: 1944-1991) is published six times a A. Michael Bloh year, in February, April, June, August, October, and December. 18 Placebo Effects in Medicine Periodical postage paid at Horsham, Pennsylvania, and addi- tional mailing offices. Thirteen dollars of each member’s annual Sara Sleigh membership fee is for a year’s subscription. Prices include post- 20 ACPE’S No Partial Credit Policy and CPE Monitor age and are subject to change without notice. Notify DIA eight 21 Preparing for an FDA Advisory Committee Meeting weeks in advance of address change with a copy of the mailing label. Back issues of most previously published issues are avail- able from DIA. SPECIAL SECTION: COMPARATIVE EFFECTIVENESS PUBLICATIONS MAIL AGREEMENT NO. 41103506 22 Making Evidence Matter in the Marketplace RETURN UNDELIVERABLE CANADIAN ADDRESSES TO CIR- 25 CER: International Developments and Impacts CULATION DEPARTMENT, PO BOX 1051, FORT ERIE, ONTARIO Judith Glennie L2A 6C7 Postmaster: Send changes of address to Global Forum, 800 The Global Push for Health Technology Assessment: 29 Enterprise Road, Suite 200, Horsham, PA 19044-3595, USA. Potential Impacts on Innovation Cover Illustration: Copyright © istockphoto.com Mendel Grobler, Eugene Salole DIA is a neutral organization that does not advocate for or against any issue. The views expressed by the individual authors or in- terviewees in the Global Forum are theirs and do not necessarily represent the views of the Drug Information Association. 6

TOC October.indd 6 9/21/11 2:52 PM 32 Managing Increasing Uncertainty: Is Conditional INDIA Reimbursement with Evidence Development the 78 New Chair for Advisory Council Future of Sustainable Health Care Systems? of India Wills Hughes-Wilson, Ana Palma Larisa Nagra Singh 36 The Role of Legislative Mandates in CER and Drug 80 DIA Selects New India Director Development William D. Marder 39 The Effect of Comparative Effectiveness Research CAREER TIPS on Drug Discovery 81 The Art of Face-to-Face Networking in a Digital Age Richard K. Harrison 41 Role of Observational Research in CER Richard Gliklich PROGRAM NOTES 45 Drug Industry, Regulators and Payers: 85 DIA 2011 Session Report: Pricing & Convergence or Divergence? Reimbursement Lloyd Sansom 87 Freda Lewis-Hall: Healthcare 48 Upcoming Events Businesswomen’s Assoc. Woman of the Year Reflects on DIA 2011

REGIONAL REPORTS NORTH AMERICA ASSOCIATION NEWS Your Topic, Time & Place: DIA In- DIA & FDA Team for Tailored Therapeutics 90 52 Coming Training Conference Chris Slawecki 57 DIA’s “NEW” 9th Annual Canadian Meeting REGULATORY UPDATES 59 Welcome Susan Cantrall, New NA Director 92 FDA Process Demystified by DIA Giovanni Furlan and Steve Douglas Course Offerings 61 DIA Opens Doors: Student Poster 95 In Memoriam: Paul Meier Presenter to Intern 96 CDER, CBER & CDRH eSubmission Michelle Pernice Updates 64 On Location: OTTAWA PATIENT PERSPECTIVE EUROPE 98 Searching for Answers and Relief: 71 12th Conference on European eDM: New Practices A Mother & Daughter’s View of the Clinical Trial Experience 72 DIA Europe Presents QRM Conference

CHINA PATIENT FELLOWS 74 Q & A with New ACC Chair 100 DIA Puts the Patient Perspective in the Center of it All 76 DIA & SAMEFA Team for 8th Latin American Congress BOOK REVIEW 102 Computerized Systems in Clinical Research

104 MEMBERS ON THE MOVE

106 MARKETPLACE

52 VOL 3 ISSUE 5 GLOBAL FORUM 7

TOC October.indd 7 9/21/11 2:52 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

DIA, CER & HTA: New Rules for a New Game

eree in the US, we’ve just begun a new use, interpreting, and then applying that data seasons of football – American football, in the real world – and creates new interfaces H notn to be confused with European among data systems and decision-makers football,football which is something completely throughout our entire health care system of different. Football may seem a curious way to patients, clinicians, and payers. What this forces introduce the topic of comparative effectiveness us to do – from the company perspective, from research, or CER, the special focus of this the regulatory perspective, and from the DIA Global Forum, but it illustrates this point: If our perspective – is to bring to bear new insights industry’s goal line, our collective “touchdown,” that we haven’t before. was once regulatory approval, then our goal line has moved. American football is a very predictable game, with people running in between clearly defined Comparative effectiveness research and health sidelines and goal lines. In the same way, the technology assessments (HTA), its European world of clinical research, and DIA’s role in counterpart, have introduced the biggest it, was relatively stable for a long time. DIA change in drug development since the legislative members and volunteers worked with thought mandates in the 1950s and ‘60s that led to the leaders around the world to improve specific formation of the modern FDA and established aspects of certain things – better statistical the predominance of randomized clinical analysis, management of the clinical trial trials. CER and HTA are changing our drug and regulatory processes, and so on – but development, approval, and commercialization our essential goal of regulatory approval has

PAUL POMERANTZ PAUL processes in fundamental ways. remained relatively unchanged. However, drug development and market access is a The placebo-controlled, double-blinded clinical fundamentally new and different game today. trial has been our only evidentiary “gold How do you play a game when the rules are still standard” – until now. But in the CER and being developed? HTA domain, we also want to know how well a given therapy does in the real world against DIA has a multifaceted game plan. Our Real established treatments. Is it better than, and how World Outcomes Task Force, co-chaired by does it measure up against, the current standard Dr. Richard Gliklich, President and CEO of of practice? We are now beginning to examine Outcomes Sciences, and Dr. Judith Glennie, more than the efficacy of a product, but its cost Director, Strategic Health Technology to the patient, the public, and to our health care Assessment, for Jannsen, Inc., has been systems as well. examining this emerging world and DIA’s place in it. Results of a survey conducted by this This trend really underlines the changing task force indicate that respondents clearly relationship between pharmaceutical product expect real world research to grow, along with development and health care systems. These a corresponding need to train professionals used to be rather distinct worlds, with the for this type of research. This task force has interface between industry and these systems provided a strong body of research which shows more of a marketing function than anything else. that industry, regulators, payers, and other

EXECUTIVE DIRECTOR’S MESSAGE But the new rules of CER and HTA result in new stakeholders, are all looking for individuals processes – gathering evidence from real world who can create the required evidence, study it, 8

ED-Exec Director's Message.indd 8 9/21/11 4:37 PM and make decisions based upon it. Education in industry, to help each constituent understand is clearly essential to navigating and thriving the others’ perspectives and develop appropriate in this new world, and DIA must grow training. More importantly, however, we can increasingly aware of the educational needs of build awareness of these issues, and trust among CER and HTA bodies and payers – and other all parties. opportunities, such as the potential to help harmonize terminology, evidentiary standards, This new world represents a very exciting and regulatory approaches – so that we can help opportunity, and changes the global landscape, our stakeholders address the challenges of this for DIA. We’re offering more on this topic in new era. our programs, including our upcoming “Making Evidence Matter in the Marketplace” program, Recently, this task force helped to lead two which grew from the efforts of our Evidence- forums of global stakeholders representing Based Medicines SIAC. We are working with industry, regulators, patients, professional the leadership of this and related SIACs to make organizations and academia, which were this program truly global, because this is truly a conducted in tandem with our EuroMeeting global challenge. in March and Annual Meeting in June. Discussion focused on the needs of stakeholders, What if you overlaid a completely new game opportunities for collaboration, and areas on top of the game already being played? How DIA can make a vital contribution. We kept does that impact the players, and/or the referees, returning to the conclusion that DIA could be umpires, or other authorities? This is the world the forum that brings CER and HTA authorities that we’re now in, and the challenge we all face together with regulators and their counterparts together. ■ EXECUTIVE DIRECTOR’S MESSAGE

VOL 3 ISSUE 5 GLOBAL FORUM 9

ED-Exec Director's Message.indd 9 9/21/11 4:37 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

technologies are no longer provided as single stand alone proprietary Are SOURCE CODE systems, but rather are developed as flexible commercial technologies, ESCROW ACCOUNTS with distribution to a large number of clients. While the contemporary ? flexibility (configurability) of these Still Needed systems has increased the importance of end user validation, the widespread Harry Huss, Randall Basinger, Richard Chamberlain, commercial nature of these types Jim McCormack, Richie Siconolfi of systems has diminished the need for escrow of source code. Vendors of these commercial systems are uring the 1980’s, regulated enthusiastic about providing their more stable than the early software industries, such as clients a copy of their software vendors and the vendor’s practices D pharmaceutical, biotech, product’s source code. Source code for protecting their own product(s) med device, other-the- was viewed as proprietary and source code have become more counter drugs, pesticides, etc., began confidential, and as such a potential reliable. to employ computerized systems to regulatory problem began to emerge. support regulated activities. This The challenge of access to software It should also be noted, that in the raised questions regarding the ability source code was not unique to FDA event a computer system requires of a company to defend the accuracy regulated companies, but had become design level or programming level and reliability of that computerized a common problem throughout most corrective action and the developer system. Validation of these systems industries. To address this potential is no longer available to the system would provide documented evidence problem, the concept of ‘source code end user, access to the software to verify accuracy and reliability. escrow accounts’ was born. To satisfy source code is typically only part However questions remained related the need to have access to software of the solution puzzle. If the end to the ability to examine the design of source code while still respecting the user of a system intends to pursue the software or to trouble-shoot a vendor’s need to maintain the design or programming activities, failed technology in the event that the confidentiality of source code, that organization will also need software developer was no longer accounts were established with programming standards used to available. Remember, at this point in neutral third parties, such as banks or develop the sources code as well time, internal software development law firms, to retain a copy of the as programmers trained in that was common. Vendor supplied source code, only to be accessed in the language. Additionally, many technologies appropriate to support event of regulatory request or when applications today are a combination regulated activities in these industry the vendor was no longer available to of modules developed for the sectors were not common. In these the client. This source code escrow completed commercial software early years, vendor developed strategy became an industry standard product. As such, access to other software was often supplied as a and has been practiced for more than licensed tools/modules may be proprietary product for a single twenty years. necessary to appropriately support company, or a limited number of the application. clients. Additionally, software As time moved forward, vendor vendors were somewhat fluid or supplied systems became common Regardless of the potential practical transient. Response to these initial place within these regulated utility challenges associated with conditions was a regulatory industries. Also with the passage exercise of source code escrow, such expectation that a company, which of time, the scope of computerized accounts are a common line item chose to employ a computerized systems expanded to include on a computerized system purchase system to support regulated activities, analytical instruments, workplace contracts. Availability of source code would be expected to have access to tools like Excel, LIMS technologies escrow is a common audit question the software source code. The that gather information from other when assessing a vendor. Escrow archival of the software source code computerized systems, network has become a “checklist question” where a company developed software technologies that serve as the without consideration regarding as an internal function was easy since backbone for all systems within the true value or viability of the the developer was a company a company, and more recently escrow account. The significance of employee and the company owned cloud technologies which serve as $750-$1500 annual fees for escrow

BEST PRACTICES the source code. However, software computerized systems for many accounts is lost in computerized vendors were generally not companies via web access. These system purchase orders reflecting 10

BP2-Source Code Escrow.indd 10 9/19/11 3:28 PM $500K-$1 million technology prices, need to establish source code escrow. indicates that approximately two- with additional 20% annual fees Additionally, a historical review of thirds of companies have source for service/maintenance contracts. the industry’s experience with source code escrow requirements and While the escrow fee for a single code escrow has revealed that escrow include escrow criteria as part of system may seem insignificant, the has questionable value. A survey of a vendor assessment. Notably, combined escrow expenditures for a escrow practices and experiences was nearly 80% of responders indicate company utilizing several hundred conducted with 29 responses from that escrow requirements could be computerized systems can become industry representatives. The survey relaxed without unacceptable risk significant. was posted to Zoomerang, with to regulatory operations or record members of the Society of Quality integrity. Perhaps most interesting This article is proposing that Assurance Computer Validation were free text comments from establishing escrow accounts for Initiatives Committee and the Drug responders indicating that escrow all vendor supplied systems can Information Association Validation was rarely or never exercised, and on now be modified. While even in Special Interest Area Community the rare occasion when escrow was today’s technology climate source invited to provide responses during exercised, the “failsafe” was often code escrow may be appropriate for the time period from May through unsuccessful. proprietary software or for products July 2011. All responses were with a very limited client distribution, collected anonymously. That survey In conclusion, this article is not reasonable risk assessment could and response tabulations are included advocating a complete rejection of be employed for widely distributed in Attachment #1 of this article. A source code escrow activities. Escrow software that would mitigate the quick synopsis of survey responses may still be appropriate under certain

Survey: Escrow of Vendor Supplied Software (Source Code) When software (and some equipment) is purchased it is normal to have the vendor establish an “Escrow” account with a law firm or bank where they agree to store the source code for each new release of the software. The goal is that if the vendor can no longer support the system, the purchaser can go to the escrow agent and obtain a copy of the source code so they can maintain it themselves.

Purpose: This survey is intended to gather information related to the practice of establishing escrow accounts for vendor supplied software

Instructions: Read the questions carefully and choose Yes or No. (Do not choose an answer if the question is Not Applicable to your company or experience)

All questions refer to systems performing regulated activities Yes No Does your company, or do your clients, have an expectation or requirement for software/source 20/29 9/29 code escrow accounts for software, of vendor supplied systems? (69%) (31%) Are software/source code escrow accounts established for applications? (Path/Tox systems, Clin 18/29 11/29 EDC, etc.) (62%) (32%) Are software/source code escrow accounts established for analytical instruments? (ClinPath 2/27 25/27 hematology/chemistry systems, Mass Specs, etc.) (7%) (93%) Are software/source code escrow accounts established for facility support systems? (Building 6/28 22/28 Automation Systems [HVAC], Security Systems, Environmental Monitoring Systems, etc.) (21%) (79%) Are expectations/requirements for software escrow included in vendor assessments? 20/29 9/29 (69%) (31%) If escrow accounts are established, are subsequent escrow verification/audit (annual, biennial, 3/27 24/27 etc.) controls in place? (11%) (89%) BEST PRACTICES Has your company ever attempted to exercise an escrow account, with circumstances where a 4/27 23/27 production system has failed, and the software vendor is no longer available? (15%) (85%) If “yes” to question #7, was the exercise of escrow successful? (ie, your company was readily able 2/6 4/6 to access the escrowed software/source code and restore the failed system to production) (33%) (67%) Based upon your experience, do you believe the expectation for escrow of vendor supplied 22/28 6/28 software/source code could be relaxed without unacceptable risk to regulated operations or (79%) (21%) record integrity?

VOL 3 ISSUE 5 GLOBAL FORUM 11

BP2-Source Code Escrow.indd 11 9/19/11 3:28 PM circumstances, such as the purchase of proprietary software, software with very limited distribution, or perhaps novel software products. However, decisions regarding escrow should not be absolute for all purchases, but rather evaluated on a case by case basis. Decisions made to establish escrow or not to establish escrow should be documented and justified. This article and the attached survey Jim McCormack Harry Huss, Executive Director results may serve as reference when Vice President Life Sciences Brandywine Compliance evaluating, “should a source code Compliance Consulting escrow account be established”? ■ Global Technology Services, IBM

There was a 10th question to the survey, asking for additional comments related to software/source code escrow accounts. The following responses were provided: t
I've worked in CSVQA for 25 years and have only heard of escrow being exercised 2 times; one time successful and one time not successful.

t
In my regulated career, as a direct employee and as a reseller of regulated software, I can remember only a handful, 2 or 3 perhaps, of RFPs with escrow requirements, and those were not followed through by the client. It Richard L. Chamberlain, Ph.D. would seem that there is no expectation of escrow requirement. One also ECS, Inc. has to look at the capabilities and staffing of the end-user to actually do something with the s/w code. In most cases, except for large companies, if a vendor went out of business, it's cheaper to continue use the s/w while looking for another vendor. It is likely that the new vendor or a consultant will have the expertise to offer a data migration also.

t
Though having the source in Escrow is a “'good idea” and provides some level of security, it rarely serves the purpose and it is unlikely that a company would be able to actually use the escrow software should the need ever arise.

t
Escrow accounts seem like such a good idea on the surface. Modern software - especially Cloud based systems like SalesForce.com- makes escrow almost a silly discussion. My customers are generally able to import data from one system to another with less trouble (to management) than RandallRRanddalll BaBasingersingerr, SeSSeniorniiorr DDirectoriir escrow. Systems Compliance Office, t
Some of the true answers are "Somtimes". With Waters and other large Global Quality Assurance, Instrument Vendors, escrow is part of their normal process/contract. Quintiles Outside of that, we don't pursue escrow for large, financially stable vendors but do require it of lesser known, specialty and/or privately held vendors where financials are suspect or software is bespoke/part of turn-key system. We haven't had to exercise escrow in recent memory and I must admit our controls for ensuring latest/greatest versions and sufficient support information are maintained in escrow are lax. Still, it's not a large cost so to Labs/Informatics and even Finance the cost of this insurance seems cheap. Cheers

t
This is a topic that is regularly discussed with vendors, that may feature in preliminary agreements, but in practice not implemented. Once with GSK we had a problem with a vendor of bespoke technology and attempted to obtain source code based on a reference in the agreement (which referred to compliance with the rule) but it did not work for jurisdictional reasons. Richie Siconolfi, Section Manager (Director) t
I have never heard of anyone testing or exercising access/restore to Validation & Quality Compliance

BEST PRACTICES escrowed software/source code. Corporate Information Security Proctor & Gamble 12 GLOBAL FORUM OCTOBER 2011

BP2-Source Code Escrow.indd 12 9/19/11 3:29 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM NANOTECHNOLOGY AND NANOMEDICINE Implications for Drug Safety, Pharmacovigilance and Risk Management

A. Michael Bloh

he advent of Applications of nanomedicine its melting point and reactive nanotechnology is include imaging and diagnosis, properties change.4 As particle size T considered to be the biggest drug delivery and other applications decreases, optical properties of engineering innovation since the (Table 1). Engineering materials nanomaterials change. Titanium Industrial Revolution.19 Study in on this scale allows for novel dioxide, a common ingredient in nanotechnology began in the 1900s, medical therapies, such as designing sun protection products, is opaque expanded slowly, then reached nanoparticle-based drugs that target (white) in its macro form. It becomes extensive growth in the later 20th cells with improved specificity, more transparent as the particle and early 21st century. resulting in decreased side effects size decreases and ultimately Nanotechnology has expanded into of the bio/pharma agent. Other becomes clear in appearance.19 For many fields including, but not limited advances are being made in medical drug delivery, not only engineered to, physics, chemistry, energy, devices and instrumentation for particles may be used as a carrier, but agriculture, electronics, and use in surgical procedures that are the drug itself may be formulated on medicine.1 A full review of the less invasive, leading to shorter a nanoscale, and then function as its complex and growing topic of recovery times and decreased risk of own carrier.15 nanotechnology and its implications postoperative infections and/or other is beyond the scope of this paper. complications. Such innovations will Safety Issues Therefore, this discussion will be improve patient quality of life, extend Nanomaterials have safety and limited to a brief overview of life expectancies, and could reduce environmental issues involved in engineered (deliberately created) the overall cost of health care.5 The their manufacture and laboratory nanotechnology and its implications revolutionary nature this technology use. Nanomaterials that escape the for drug safety, pharmacovigilance, suggests an immense future market.7, 18 laboratory or manufacturing site can and risk management. enter the environment. Then they Because of their diminutive size, may deteriorate or become free to Because of the many facets nanomaterials have an increased interact unpredictably with anything, of nanotechnology, there are surface area. Their physical, chemical potentially creating unknown several application-dependent and biologic properties can change environmental hazards. Because definitions. A common definition unpredictably and be different from of the limited knowledge about is the manipulation of matter in their bulk counterparts. There are nanomaterials, organ toxicity, tumor the structural size range of 1 to 100 no product class distinctions with development and immune responses nanometers (nm). A nanometer nanomaterials. A 10nm particle are possible concerns with exposures is one-billionth of a meter or may have different properties through the routes discussed below.3, 18 BEST PRACTICES 1/100,000th of a millimeter.8, from a 20nm particle of the same 9, 11 Figures 1a and 1b provide material.5 Nanogold is being studied Inhalation Route a comparative perspective of for cancer, antibiotic use and its Inhaled nanomaterials can aggregate nanomaterials. other unique nanoproperties. Above in the alveoli where their increased 60nm in particle size gold retains surface area places a burden on Nanomedicine and nanomaterials its known properties. However, mucociliary and macrophage used in medicine can take many below that size nanogold’s color clearance. While in the lung, forms within this structural range. changes from gold to red and nanomaterials may translocate to

13

BP1-Nanotechnology.ver3.indd 13 9/19/11 3:36 PM Figure 1a. Relative Size of Nanoparticles Compared with Familiar Items17 the systemic circulation. Inhaled nanoparticles can also gain access to the CNS via olfactory nerves.3

Dermal Exposure Nanosized particles may penetrate more deeply into the skin than their larger counterparts. It has been hypothesized that nanoparticles of titanium dioxide (5-20nm) can penetrate the skin and enter the immune system or the systemic circulation. Quantum dots have been shown to penetrate porcine skin within 8 hours of application.3

Figure 1b. The sizes and shapes of some nanomaterials as compared to more Oral Route familiar materials. Shown for comparison are materials that are below, within, Uptake of nanoparticles after oral and above the nanoscale range, to put nanomaterial size in perspective.18 exposure depends on particle size and surface chemistry (certain nanoparticles are combined with other materials). In rats, 50nm to 3 um particles were detected in the liver, spleen, blood and bone marrow after oral exposure. Particles >100nm did not reach the bone marrow and particles >300nm did not reach the blood, suggesting that nanoparticles of lesser size have been detected in bone marrow and blood. Nanomaterials can be used to enhance the GI absorption of a pharmacologically active compound.3

Figure 2. Multifunctional nanoparticle. The nanoparticle’s “corona” can be Pharmacokinetics functionalized with hydrophilic polymers, targeting molecules, therapeutic drugs, The pharmacokinetics of non- and image contrast agents. The interior core can be solid (e.g., quantum dots) or biodegradable nanomaterials has liquid (e.g., liposomes). Molecules are not shown to scale. PEG, Polyethylene glycol.17 not been studied in detail and there are only a few studies focused on the removal of nanomaterials from organisms. Nanomaterials can potentially accumulate over a lifetime in an organism. Some nanomaterials may not be cleared by the reticulo-endothelial system and may accumulate in the liver. Larger nanomaterials may not pass through the glomerular filter. Nanodendrimers of 5nm were reportedly excreted in animal urine but also accumulated in the kidney.3

Genotoxicity and Carcinogenicity Nanomaterials can enter the cell and,

BEST PRACTICES in some cases, the nucleus where it’s

14 GLOBAL FORUM OCTOBER 2011

BP1-Nanotechnology.ver3.indd 14 9/19/11 3:36 PM possible for them to interact with nanomaterials including carbon effects in clinical laboratory tests, inter-nuclear processes where DNA fullerenes, carbon nanotubes, and drug interactions, dose, hepatic damage may occur. While useful nanoparticle metal oxides. ROS and and renal impairment, special in concept to cancer treatments, free radical production is one of the populations (eg pediatrics, elderly), the genotoxic effects on normal primary mechanisms of nanoparticle interactions with other existing cells must be considered. Carbon toxicity. It may also result in pathologies, interactions with foods nanotubes (CNTs) administered to oxidative stress, inflammation, and and over-the counter-products. To mice demonstrated genotoxic results consequent damage to proteins, the chagrin of consumer advocacy that were similar to those of asbestos. 3 membranes and DNA. Size is groups, at this time the FDA, not the only variable influencing EMEA, and MHRA do not believe Development the safety of a nanomaterial. that additional regulations are Nanomaterials have been shown Chemical composition, shape, required to manage the licensure to cross the placenta in rats surface structure, surface charge, of nanomaterials/medications.3, 5, 12, suggesting a risk to the developing aggregation, solubility, and the 13, 15 While unrelated to the clinical fetus. Carbon nanotubes (CNT) presence or absence of functional safety evaluation of nanomedicine, have induced changes, in vitro, groups of other chemicals can also insurance providers may consider in the cell proliferation and other contribute.6 Figure 2. expensive nanotreatments as cellular activities suggesting in-vivo “experimental” or environmental consequences in development.3 Products in Use Today hazards and outside the scope of Nanotechnology and nanomedicines coverage of certain health insurance Immunological responses are in use today. Many cosmetics and policies.20 Nanomaterials have demonstrated sunscreens use nanosized ingredients both positive and negative effects (eg nanotitnium dioxide, nanozinc Summary on the immune system that oxide).12, 13 Currently, nanoenabled The current safety track record differ for inorganic and organic drugs have been approved by the for nanomedicines is without nanotypes. These effects may be FDA for the treatment of cancer. clinical problems so far. However, desirable or undesirable. Therefore, Examples include Abraxane®, which because of rapid expansion in nanomedicine testing should is used to treat breast cancer and the area, much remains to be exclude undesirable immunological Doxil® for ovarian cancer.5 discovered. Nanomaterials bio/ responses. In general, positively pharma properties are different charged (cationic) particles are more Safety Challenges from their macro counterparts. likely to induce acute inflammatory Laboratory and manufacturing Currently, there are no nanomaterial reactions (innate reaction) than workers may be at risk for accidental class distinctions. The use of negatively charged (anionic) exposures through dermal, nasal, nanomaterials in the laboratory and particles. Two parameters, size and ophthalmic and oral routes. manufacturing process may require surface charge, play a central role Topically applied sunscreens “nanoproof” protective equipment in these responses. The phagocytic and cosmetics that contain to prevent inadvertent exposures. activity of macrophages in the lung nanomaterials, when washed off, Environmental implications has also been linked to particle size. enter water ecology with unknown regarding nanomaterials need to be Although micrometre-sized particles repercussions. Nanomedications reviewed and updated, especially stimulate phagocytosis, smaller and nanaomaterials may confound waste water testing standards. nanometer sized materials often do the safety evaluation of bio/ The environmental impact of not. Such particles may even reduce pharma agents to which they are nanomaterials and metabolites is the capacity of the macrophages.3 combined. Nanomedications and largely unknown. bio/pharma products combined with With nanoparticles, the smaller they nanodelivery systems may present The implications for drug safety, are, the greater their surface area to unique safety issues. The preliminary pharmacovigilance, and risk BEST PRACTICES volume ratio and the higher their evaluation of many products is management are as limitless as chemical reactivity and biological performed in normal animals and the possible applications of the activity. The greater chemical humans. However, sick individuals technology. Nanomaterials and reactivity of nanomaterials can result can be prone to unforeseen toxicities. nanomedicines will require specific in increased production of reactive Studies need to focus on therapeutic safety evaluations on a case-by- oxygen species (ROS) including effect as well as nanoparticle case basis for their use in humans. free radicals. ROS production has disposition.15, 18 Nanomedications Clinical research will need to focus been found in a diverse range of need to be evaluated for their not only on therapeutic safety

VOL 3 ISSUE 5 GLOBAL FORUM 15

BP1-Nanotechnology.ver3.indd 15 9/19/11 3:36 PM and effectiveness, but also on with a medical use. Regulators do their environmental and clinical nanomaterial impact and disposition. not want to see nanomaterials turn safety profiles. Pharmacokinetics for active moieties, into the 21st century’s “asbestos”.18 nanomaterials, and metabolism of The US EPA is taking a new path Acknowledgements both will need to be studied. Present forward in the regulation of Thanks to Edward Sharples BA, concepts of risk detection may not manufactured nanomaterials under MBA for his thoughtful editorial apply to nanomedications, especially the Toxic Substances Control Act comments. in long-term exposures and effects (“TSCA”). Revised regulations or use in individuals with impaired are expected in the near future.14 FDA recognizes the role of health.15 Current regulations may or Nanotechnology, nanomaterials, nanotechnology. In June of 2011, may not be adequate in managing and nanomedicines currently under the FDA issued a draft Guidance for nanomaterials’ licensing process development represent a revolution Industry: Considering Whether an for commercial use. Current US in the visualization, diagnosis and FDA-Regulated Product Involves the labeling requirements do not treatment of many diseases. While Application of Nanotechnology. This stipulate that nanomaterials are current commercial and medical publication is open for comment used in a product.3, 5, 10, 11 However, applications of nanotechnology through August 2011. (http://www. health authorities should always be appear to be “safe”, in this rapidly fda.gov/RegulatoryInformation/ notified early in the development growing and promising area, much Guidances/ucm257698.htm, accessed process if nanotechnology is involved remains to be revealed regarding 12Aug2011) Table 1. Classes of nanomaterials for use in medicine2

Type of nanomaterial/ Potential Medical Use Disease state Basic description

Liposomes Drug delivery system Cancer Spherical nanoparticle, lipid bilayer membrane, hollow interior

Nanopores Permits nutrients but limits Transplanted tissue, genetics 20nM pores immune penetrations Fullerenes, Encapsulates radioactive material, Imaging procedures, antibiotic with light “Soccer ball” framework transport antibiotic, antiviral, stimulation, infection, HIV, Cancer anticancer products Nanotubes Drug delivery, Amphoteracin B, Can penetrate the cell wall, Fungal, Cancer therapy, 1-25nm tubes with and DNA transport, increasing vaccines without “caps” immune response

Quantum dots Drug delivery by conjugation, Diagnosis and treatments, Prostate cancer, 2-10nm nanocrystal Melanoma, Breast Cancer Nanoshells Immunologic manipulation Cancer, Immunoglobulin determinations Silaca core and thin metallic shell Nanobubbles Drug transport, combined with Cancer, increased uptake by target cells. Vascular Nano scalled bubble heat or ultrasound clearing Paramagnetic Diagnostics, Imaging, rapid cell MRI imaging, Cancer nanoparticles uptake (e.g. iron Nanosomes Targeted diagnosis and treatment, Brain cancer Silaca coated iron oxide combined with laser nano particles with targeted antibody and contrast elements

Dendrimers Drug transportation within the Gene therapy, Anti-retroviral, Nanomolecule with branch “cavities” Type 1 Diabetes, branching structures Potential for intra-nuclear cancer applications Respirocytes Deliver up to 236x more oxygen Cardiac arrest

BEST PRACTICES Nano device than RBC Hypothetical RBC

16 GLOBAL FORUM OCTOBER 2011

BP1-Nanotechnology.ver3.indd 16 9/19/11 3:36 PM References Scale of Things Accessed 20Apr2011 1. History of Nanotechnology National Nanotechnology 15. DeJong, WH, Borm, PJA Wikipedia Initiative Drug Delivery and Nanoparticles: http://en.wikipedia.org/wiki/ www,nano.gov/html/fats/The_ Applications and Hazards. History_of_nanotechnology, scale_of_things.html, Accessed International Journal of Accessed 26Apr2011 20Apr2011 Nanomedicine 2008:3(2) 133-149 2. Surendiran A. Sandhiya, S, 10. Progress toward Safe 16. McNeil, S. Pradhan SC, Adithan, C Nanotechnology in the Nanotechnology for the biologist Novel applications of Workplace, A Report from J. Leukoc.Biol. 78: 585–594; 2005 nanotechnologies in medicine the NIOSH Nanotechnology 17. Robert A Yokel1*, Robert C Indian J Med Res 130, December Research Center (NTRC)Project MacPhail2 2009, pp 689-701 Updates for 2007 and 2008, Engineered nanomaterials: 3. Hoet P, Legiest B, Geys J, November 2009 US Centers for exposures, hazards, and risk Nemery N Disease Control (CDC) http:// prevention Do Nanomedicines Require www.cdc.gov/niosh/docs/2010- Journal of Occupational Medicine Novel SafetyAssessments to 104/pdfs/2010-104.pdf, Accessed and Toxicology 2011, 6:7 Ensure their Safety for 20Apr2011 18. Gwinn MR, Vallyathan V Long-Term Human Use? 12. Approaches to Safe Nanoparticles: Health Effects— Drug Safety 2009; 32 (8): 625-636 Nanotechnology, Managing the Pros and Cons Environ Health 4. Alanazi FK, Radwan AA, Health and Safety Concerns Perspect 114:1818–1825 (2006) Alsarra IA Associate with Engineered 19. What is nanotechnology? How Biopharmaceutical applications of NanomaterialsNational Institute do properties change at the nanogold for Occupational Savety and nanoscale? Saudi Pharmaceutical Journal Health (NIOSH), US Centers for Anonymous (2010) 18, 179–193 Disease control (CDC) March www1.mengr.tamu.edu/ 5. Pautler M, Brenner S 2009 http://www.cdc.gov/niosh/ MESAM/Teaching/ Nanomedicine: promises and docs/2009-125/pdfs/2009-125.pdf IntroductiontoNanomaterials/ challengesfor the future of public , Accessed 20Apr2011 Week%2002-Size%, Accessed health 12. Nanomateials, Sunscreens and 26Apr2011 International Journal of Cosmetics: Small Ingredients Big 20. Insurance Coverage for Nanomedicine 2010:5 803–809 Risks Nanotechnology Risks Could Be a 6. Nel, Andre; et al. Friends of the Earth (FOTH 2006) Big Deal Toxic Potential of Materials at the http://www.foeeurope.org/ Amy Fink, August 31, 2010 Nanolevel. activities/nanotechnology/ http://insurancecoveragemonitor. Science 311 (5761): 622–7, (3 nanocosmetics.pdf, Accessed com/enviro-toxictort/insurance- February 2006) 26Apr2011 coverage-for-nanotechnology- 7. Nanotech Rx: Medical application 13. Nanotoxicity: Nanomaterials risks-could-be-a-big-deal/, of nanoscale technologies: in Cosmetics Contribute to Accessed 27Apr2011 ■ What impact on marginalized Enviornmental Pollution communities ETC group 2006 Nano Patents and Innovations, http://www.etcgroup.org/ Sunday, October 18, 2009 upload/publication/593/01/ http:/nanopatentsandinnovations. etc06nanotechrx.pdf, Accessed blogspot.com/2009/10/ 20Apr2011 nanotoxicity-nanomaterials- BEST PRACTICES 8. Nanotechnology in-cosmetics.html. Accessed National Health Laboratory 26Apr20111 Services 14. Control of Nanoscale Materials www.nioh.ac.za/?page=nano under the Toxic Substances technology&id=76, Accessed Control Act, US Environmental 20Apr2011 Protection Agency 9. Nanotechnology Facts – The http://www.epa.gov/oppt/nano/, Michael Bloh

VOL 3 ISSUE 5 GLOBAL FORUM 17

BP1-Nanotechnology.ver3.indd 17 9/19/11 3:36 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

PLACEBO EFFECTS IN MEDICINE New Challenges for the Pharmaceutical Industry

Sara Sleigh

lacebo effects cause the ‘non-specific’, are more likely to be assumption is that the extent of any pharmaceutical industry no the ‘specific’ effects of healing rituals. placebo effects will be the same in P end of practical problems. both groups of patients and can be Over the past few years, Neurobiological studies, including subtracted from any pharmacological unexpectedly high rates of response those with functional MRI and effect of the drug (Figure 1). The in placebo groups have troubled positron emission tomography difference between the treatment clinical programs in Crohn’s disease, (PET), have uncovered some basic groups may be used to inform schizophrenia, depression and pain mechanisms for placebo effects, clinicians of a drug’s effect size. amongst others. Senior industry including the involvement of However, neurobiological evidence figures have highlighted scientists’ endogenous opioids in placebo and meta-analyses suggest that the lack of understanding of placebo analgesia and cholecystokinin assumption is not always valid and response as a key challenge for the in nocebo hyperalgesia, and the that the difference between active industry. neuronal circuit affected by placebos in Parkinson’s disease. In other cases, drug and placebo may represent an Research carried out over the past endocrine, immune or autonomic over- or an under-estimate of the two decades has shed new light on nervous system responses have drug’s true efficacy, depending on the the psychobiological phenomena been observed following placebo context of the trial. responsible for improvements seen administration, conditioning and in groups of patients who receive verbal suggestions aimed at altering a Placebo researchers stress that placebos in clinical trials. This patient’s expectations. different ways of testing drugs should research has shown that the physical be considered in order to better form of the treatment is important: The media has shown a growing control for placebo effects. A wide large pills are better than small ones; interest in placebo effects following range of different approaches could four pills are better than two; colour analyses of different types of be introduced in RCTs, or through is important, but in different ways alternative medicine, such as innovative new trial designs, some of in different patient populations; acupuncture and homeopathy, which are listed here: branding can affect results; injections as well as anti-depressant drugs. work better than pills and, surgery These analyses conclude that a large t
Provision of more explicit may be best of all. More important portion of the therapeutic response instructions in protocols as to how are the culture and context in which to these treatments is due to sites should manage interactions the treatment is given. A patient’s placebo effects and raise important with patients during the trial. At motivations, previous experiences questions for companies and those present, sites decide how much and expectations contribute to the who regulate them. Many questions time is spent with a patient and effect, which may be altered by a relate to how best to translate this who the key contact may be physician’s own expectations and understanding of placebo effects into their verbal suggestions, or from improvements in clinical practice. (e.g., study nurse or principal advertising or media coverage. For pharmaceutical scientists, investigator). Indeed, patients’ and physicians’ however, research questions may be expectations of a drug’s effectiveness different. t
Inclusion of a third group in may vary between countries or which patients would receive no change over time. Expectations can Research into placebo effects treatment but interactions between also have negative, or nocebo, effects. challenges assumptions underlying the patient, study investigators and

BEST PRACTICES Researchers conclude that placebo randomized, double-blind, placebo- the treatment environment would effects, which are often described as controlled trial (RCT) designs. A key be same for all three groups. 18

BP3-Placebo Effects.indd 18 9/19/11 11:28 AM t
Possible use of an ‘active’ placebo designs are already used in studies of pain (the EUROPAIN project). that mimics the side effects of with healthy volunteers. In another In the US, a consortium led by the the active treatment to improve suggested design, patients would be Coalition Against Major Diseases control over bias introduced by allowed to choose on a daily basis at the Critical Path Institute has patients when they determine their between an active drug or placebo recently delivered a new quantitative treatment allocation accurately treatment, whilst being prevented model of Alzheimer’s disease (i.e., ‘break the blind’). from taking both by technical means. progression. The outcome of the study would t
Assessment of whether or not relate entirely to the behavioural Statistically and clinically significant patients in the trial have broken choices of the patient, although differences between an active the blind, which would help to biomarker testing could also be treatment and placebo in RCTs form clarify the extent of any bias within included. This interesting suggestion the basis of regulators’ decisions on the trial and improve trial validity. would not be applicable in all drug efficacy. Regulatory guidelines situations and has yet to be tested. reflect this. A key challenge for both t
Use of innovative designs that the regulators and the industry is, include multiple drug/placebo The pharmaceutical industry is therefore, to integrate this growing phases that alternate, with or undertaking analyses of their own understanding of placebo effects without washout periods in data from patients who received and their role in healing to improve between. placebos in clinical trials to build therapeutic options available to better models of disease progression. patients. ■ Other considerations for trial design These models could be used in include the fact that placebo effects clinical trial design and simulation in appear to be larger in all treatment an attempt to improve the chances of groups in comparator trials and clinical trial success. Each project is unbalanced designs including both run by consortia including the largest active comparator and placebo companies, demanding high levels of groups. In addition, placebo effects cooperation and data sharing, again have been shown to be maintained highlighting the extent to which the over long periods in a variety of practical problems caused by placebo different settings. Clinical trials that effects are recognized. The DDmoRe aim to wash out placebo effects by consortium in the EU is focusing on increasing trial length may not be type 2 diabetes and oncology, whilst appropriate. The role of informed another consortium also sponsored Sara Sleigh is a Freelance Writer and consent in determining the extent of by the Innovative Medicines can be contacted at (sara.sleigh@ placebo and nocebo responses also Initiative is developing new models btopenworld.com). deserves closer attention. Placebo researchers are placing considerable emphasis on these ethical Figure 1. Hypothetical drug and placebo effects in treatment groups in clinical considerations and they will form an trials: the assumption in RCTs and a possible alternative scenario integral part of the program for an international conference on placebo effects in 2012.

Whilst these measures may improve the ability to decipher real treatment effects in RCTs, several trial designs have been put forward in the experimental setting to better understand placebo effects. These include the balanced placebo BEST PRACTICES and balanced cross-over designs, both of which involve providing false information to patients or volunteers about the treatment(s) they will receive. This raises obvious ethical concerns but, in the experimental setting at least, these may be overcome through the use of ‘authorized deception’ and the

VOL 3 ISSUE 5 GLOBAL FORUM 19

BP3-Placebo Effects.indd 19 9/19/11 11:28 AM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 ACPE’S NO PARTIAL CREDIT POLICY AND CPE MONITOR: What Does This Mean for a Pharmacist?

IA offers a variety of multiple “activities” or Universal NABP. Pharmacist and pharmacy continuing education Activity Numbers (UANs) with the technician participants will provide D activities, including appropriate number of continuing their NABP e-Profile ID and date continuing pharmacy education. As pharmacy education contact hours. of birth (in MMDD format) to an accredited provider, DIA must Additionally, each UAN will also the ACPE-accredited provider for ensure compliance with the identify the type of activity it is, i.e., that activity when they register for guidelines of each accrediting body knowledge-based vs. application- the event or submit a request for in order to maintain its accreditation based, and will be designated with credit. Within four to six weeks status. This article will highlight the appropriate topic identifier. after each continuing education recent policy changes impacting activity, accredited providers will DIA’s Accreditation Council for Learner attendance will be validated then be required to submit the Pharmacy Education (ACPE) for each educational activity. following data for pharmacist and accreditation status. DIA utilizes sign-in sheets and/ pharmacy technician participants: or scanners to validate attendance ACPE Policy Update: No at CPE activities. Attendance activity UAN, NABP e-Profile ID, Partial Credit validation will be reflective of the date of birth (MMDD) and date The ACPE recently announced credit designation level for the of participation. Pharmacist and a policy change effective July 1, educational events as outlined above pharmacy technician participants 2011, in which ACPE-accredited (full-day, half-day and/or session will be able to view their continuing providers are no longer able to offer level). It is imperative that learners pharmacy education transcript via partial credit for certified pharmacy review the information on how to the CPE Monitor system. The CPE education (CPE) activities. This obtain continuing education credits Monitor will eliminate the need for has a significant impact to DIA’s for each CPE activity in which he/ providers to provide electronic or educational activities. In the past, she participates as the attendance paper statements of credit. The new if DIA held a two-day conference validation requirements will vary for tracking system will make CPE data that offered 12 pharmacy contact each activity. This information can be available to the boards of pharmacy hours, and a learner only attended found on the activity brochure and where the learner is licensed or six hours of the conference, he/she in the continuing education tab with registered. could receive continuing education the activity information included on credits for six contact hours. the DIA website. The ACPE and NABP are According to the new policy change, currently piloting the program. a learner would not be able to receive CPE Monitor Implementation of the CPE Monitor a statement of credit for six contact The ACPE and the National system and for the ACPE-accredited hours if the continuing education Association of Boards of Pharmacy provider to collect the pharmacist activity offered 12 contact hours. (NABP) are developing a national and pharmacy technician participant electronic system to store and e-Profile ID and date of birth when DIA has been evaluating the various authenticate data for completed CPE registering for a CPE activity is types of educational activities units for pharmacists. The goal is offered to determine the best to provide a streamlined reporting scheduled to begin in late 2011 or way to manage the designation of process for CPE providers and a early 2012. DIA will be modifying continuing education credits. In compliance verification process its registration form and database to order to ensure learners are able to for participating state boards of collect the e-Profile ID and date of receive continuing education credits pharmacy. birth for pharmacists and pharmacy for their participation in a multi-day technician participants when event, DIA will begin to designate Pharmacists and pharmacy registering for one of its activities. continuing education credits at the technicians will receive a unique To learn more about the CPE

BEST PRACTICES full-day, half-day, and/or session identification number (ID) after Monitor, please visit http://www. level. DIA events will include setting up their e-Profile with acpe-accredit.org/cpemonitor. ■ 20

BP4-ACPE's.indd 20 9/19/11 11:30 AM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

Preparing for an FDA ADVISORY COMMITTEE MEETING acing an FDA Advisory Committee meetings continue Committee (AdComm) is a to grow in both frequency and F stressful moment for any importance. REGISTER FOR DIA’S drug team. After presenting a short, NEW TRAINING convincing argument for approval, More than 50 to 60 AdComms are COURSE ON the team must answer a barrage of held each year and recent legislation THIS TOPIC! questions from a panel whose vote and guidances virtually ensure could spell the success or failure of that these numbers will increase. their product, or company. The 2007 FDA Amendments Act Preparing for a US FDA (FDAAA) mandates an AdComm for Advisory Committee Some think preparing for an any new molecular entity, while the Meeting AdComm involves an intensive few 2008 Guidances for the Public and weeks of work before the hearing. In FDA Staff on Convening Advisory October 20, 2011 fact, smart preparation actually Committees encourage consideration Horsham, PA begins four to five months in of a hearing if a drug is controversial advance, as there is much work to be or of public interest, or if special For more information, visit the done. expertise is needed to evaluate it. DIA website at www.diahome.org, select Training, Teams must be built, external experts Moreover, ever since Vioxx, there’s Find an Educational Offering, engaged, timelines created, and roles been an increasing focus on safety and search ID 11442 assigned. A briefing package and a and risk management by both the series of presentations (on efficacy, agency and the panels: the FDAA, in safety, etc.) must be written and fact, mandated the creation of a risk The Steps to Preparing for sharpened. Hundreds, sometimes communications committee. a Successful FDA Advisory thousands, of slides must be Committee Meeting BEST PRACTICES created, and the answers to dozens Appreciating the growing of questions must be rehearsed in importance and complexity of November 14, 2011 “mock panels” designed to expose the Advisory Committees, teams about 11:00am-12:30pm ET team to lifelike hearing situations. to face one might remember Henry Ford’s wise counsel on preparation: DIA # 11251 Such in depth preparation is all the “Before everything else, getting ready more important given that Advisory is the secret of success.” Indeed . ■

21 21

AN3-AdComm.indd 21 9/19/11 4:47 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

MAKING EVIDENCE MATTER IN THE MARKETPLACE

n November 3-4, the This conference is being to you, and who determines RenaissanceR Washington developed by the EBM “value,” in these conversations? O DCD Hotel will host Making SIAC, of which you serve on the Evidence Matter M in the Marketplace: Core Committee. Why did you Applying Comparative Effectiveness decide to chair the program This is an important question to Health Technology Assessments committee for this conference, and and, at the same time, an in Real-world Settings, a program how have you shared your respon- overly broad way of talking about developed by DIA’s Evidence-Based sibilities and interests between this things that are very specific. At a very Medicine (EBM) Special Interest SIAC and conference program high level, I operationalize “value” as Area Community (SIAC). committee? being “that which drives action,” whether that action is something you Discussion of comparative want to see from people who are effectiveness research, and its It’s a good, symbiotic, ap- making a decision to use certain application within health technology proach to working with DIA. technologies at either the patient or assessment, is not new. But emerging The EBM SIAC’s focus is really at the provider level, action at a payer level, standards for evidence evaluation core of what this meeting is about, to or even action at a pharmaceutical or development by leading payers, such an extent that spending most of device level – for manufacturers to along with the recent formation of my time in planning this meeting and decide where to invest research the Patient-Centered Outcomes talking about it within our SIAC and dollars in the future technologies Research Institute (PCORI) and with other SIACs easily dovetails the that will benefit those patients. similar health care reform initiatives, two efforts. It all comes together in have made understanding this the fact that, over these two days, For that question of “value,” the application more important than this meeting will feature sessions and unifying factor to me is, “What do we ever. As a result, this program has experts talking about these same need to see in order to drive change?” been designed to provide attendees issues. There are multiple levels I try to think with practical, “what it means for about. In terms of industry change: me” ideas that they can apply within It is a bit of a challenge. Sometimes How do we get industry to invest in their own drug development and you have to make decisions about an area? That’s a question of value marketing programs. timing, and what you can do all at – how do you make industry value once. But ultimately, by the end investing in oncology versus invest- Along with the EBM SIAC, this of the year, this meeting will help ing in Alzheimer’s versus investing program was developed by Dr. position those areas of most inter- in cardiovascular? If the question is Sean D. Sullivan (Professor of est to our SIAC and to those SIACs about a payer, the question may be Pharmacy & Public Health; Director, that are close to us methodologi- how you get them to value treatment Pharmaceutical Outcomes Research cally, and set those up so that, first, option “A” over treatment option “B.” & Policy Program; and Associate we’re clear on their importance and The same applies to doctor/patient Dean for Research, School of impact on drug development and, interaction: How do you get them to Pharmacy, University of Washington) second, the efforts our SIAC wants value a certain approach to treat- and Craig A. Hunter, MPP, PGCP to make are in a better position to be ment, or an appropriate diagnosis and (Senior Research Scientist, Eli Lilly understood by a larger community. application of technology, given the and Company), who also serves on uncertainties that exist in the medical the EMB SIAC Core Committee. community? So that’s the high-level Craig shared his thoughts on this The word “value” is essential “value”: Value is what drives action. meeting and related topics in the to these EBM / CER discus-

COMPARATIVE EFFECTIVENESS COMPARATIVE following Q&A. sions, but what does “value” mean For this meeting, this concept is

22

SS8-Making Evidence Matter.indd 22 9/20/11 5:34 PM operationalized and focused on Absolutely not – in fact, the doing in terms of looking at both health technology assessment and economic or financial value in efficacy and effectiveness at the same the industry/payer interaction, so the many cases is the “easy part” of what time. We’re talking about how definitions of “value” that are going we do on a day to day basis – that is, private payers are using unique to be discussed will be very specific concepts of cost effectiveness, budget reimbursement mechanisms. Just as to how people can pull these differ- impact models, and other cost-fo- importantly, each of these sessions ent aspects of defining “value” into cused approaches are fairly well will bring these ideas back into focus their day-to-day drug development understood methodologically and, on on drug development. We’re not just or drug reimbursement opera- a basic level, viewed similarly across saying, “Here’s what you could read tions. As you go through the seven stakeholders. This meeting is set up in a trade magazine and find out on sessions on our agenda, you’ll see to account for economic realities your own.” We’re taking you to the research topics such as heterogene- associated with defining value, but next step: “What does this mean for ity of treatment effects, which will will by no means focus on them or you?” ask the question of how you properly even claim that they’re the “impor- define and demonstrate value in tant piece” of this equation. This may mean that you have to research. Though other sessions we’ll design your studies in a certain way, bring patient-reported outcomes or should be considering certain (PROs) into that conversation as What “value” do you hope options that FDA and CMS are well. You’ll see value-based insur- attendees receive from exploring. Or perhaps you need to ance design and performance-based attending this conference? understand that the definition of reimbursement – how are payers value that you’re building into your uniquely identifying value and how phase 3b study is not going to be are they integrating that into cover- More than anything, this the same definition that’s used when age and reimbursement decisions? meeting has been developed evaluating your study inside a value- We’re going to look at things like the to be distinct from the litany of based insurance kind of design. It’s principles of conducting comparative meetings over the past few years that bringing these topics home to our effectiveness research and translat- have focused simply on definitions of day-to-day work, so that attendees ing that research between different value, of comparative effectiveness, not only understand these topics but groups: How do you make sure, once of HTA, and theoretical arguments know what they can do about them. you’ve developed that value, that you of what these things might mean in COMPARATIVE EFFECTIVENESS deliver it in such a way that others terms of drug development and can understand and accept it? Our reimbursement, without actually What else would you like to goal is to take that value definition – giving the individuals who attend share with our readers about of driving an action – and building it anything more than a high- or this upcoming conference? out to make something tangible, so mid-level understanding of the issues that when people leave this meeting, on a “perfect world” kind of basis. they’ll not only have a sense of value This meeting is meant to give people The first is to make it clear and the way it is defined, but how to an understanding of where these that while we’re looking at the start creating it in their own work. concepts are actually being used and impact of these ideas on drug applied – their real world applica- development and reimbursement, I tion. So we’re talking about heteroge- want to make sure that no one It sounds like these discus- neity and patient reported outcomes assumes that you have to be a sions will primarily but not (PROs). We’re talking about what methodologist – an “in the trenches” exclusively or prohibitively mean FDA and CMS (the Centers for researcher, or someone making payer economic or financial value? Medicare & Medicaid Services) are decisions – to see its value. In truth,

VOL 3 ISSUE 5 GLOBAL FORUM 23

SS8-Making Evidence Matter.indd 23 9/20/11 5:34 PM these realities impact people at many The other thing to note is that to our actual work, and make this different levels within industry as discussion will play a primary role a more impactful and meaningful well as within the payer community. in this meeting. In the same breath opportunity. ■ The topics discussed will likely be of that I’m going to encourage a wide interest to both the policy and range of people to attend, I’m going patient communities as well; policy to encourage them to participate groups, especially, tend to have a once they’re there. Sessions are very good sense of what’s happening being set up as interactive panels: with things like PCORI (the Patient- Each session will feature multiple Centered Outcomes Research thought leaders, but each thought Institute) and other federal initia- leader has a specified time limit for tives, though at times I think there their individual presentation, to can be a disconnect between that ensure that those in attendance play view from ten thousand feet and how their own part in this discussion these concepts actually impact drug process through sharing experiences development. It’s important for or asking questions specific to their people to understand that there’s a interests and needs. I’m hopefully wide range of applicability for the this will make the meeting even more Craig A. Hunter, MPP, PGCP, Senior things we are going to discuss. beneficial to our professional lives, Research Scientist, Eli Lilly and Co. COMPARATIVE EFFECTIVENESS COMPARATIVE

24 GLOBAL FORUM OCTOBER 2011

SS8-Making Evidence Matter.indd 24 9/20/11 5:34 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

CER International Developments and Impacts

Judith Glennie

Introduction Figure 1. Relationships Among Concepts: HTA, CER, and EBM

esearch and lay literature sources of recent years R have increasingly containecontained commentaries and papers related to some aspect of comparative effectiveness research (CER). While much of the recent volume has been driven by the creation of the Patient-Centered Outcomes Research Institute (PCORI), the concept of using comparative evidence to inform patient care decisions is by no means new.

The paradigm of evaluating evidence to determine options – at both a patient and a population level – has been actively applied in an increasing number of countries around the world over the past two to three decades. Australia CER vs. HTA vs. EBM, etc. etc. and ethical implications of and Canada were amongst the The consistency of definitions is a development, diffusion and use of first to apply the concepts of real challenge in the comparative health technology.”3 comparative clinical and economic evidence assessment domain. assessments to population-based Having a common language is t
A broad-based assessment decision making for government- imperative to having informed that can include evaluation of funded drug benefit programs. debate on the issues of importance relative safety, efficacy, real- Sweden, Spain, and a number to stakeholders. Many of these world effectiveness, cost, cost- COMPARATIVE EFFECTIVENESS of other European countries terms are closely related but at the effectiveness, as well as social, have a long tradition in health same time cover different aspects of legal, ethical, and political technology assessment (HTA) to the field of evidence assessment, as implications of a technology inform policy makers. And the depicted in Figure 1 (adapted from previous US General Accounting Luce et al). Comparative Effectiveness Office – known as the Government Research (CER) Accountability Office (GAO) since The following outlines some key 2004 – has been engaged in HTA terms and summary definitions t
“CER is the generation and through the years. All of these pulled from a variety of sources. 1,2,3,4,5 synthesis of evidence that initiatives – in one way or another compares the benefits and harms - pulled from a theoretical basis Health Technology Assessment of alternative methods to prevent, in decision analysis, originally (HTA) diagnose, treat and monitor a developed to support more clinical condition, or to improve systematic assessment and decision t
“…a multidisciplinary field of the delivery of care. The purpose processes for a wide variety of policy analysis, studying the of CER is to assist consumers, fields. medical, economic, social clinicians, purchasers, and 25

SS7-Glennie.indd 25 9/20/11 5:33 PM Figure 2. PCORI’s Patient-Centered Outcomes Research (Working Definition) July 2011

Patient-Centered Outcomes Research (PCOR) helps To answer these questions, PCOR: people make informed health care decisions and allows their voice to be heard in assessing the value of health t
Assesses the benefits and harms of preventive, diagnostic, care options. This research answers patient-focused therapeutic, or health delivery system interventions to questions: inform decision making, highlighting comparisons and outcomes that matter to people 1. “Given my personal characteristics, conditions and preferences, what should I expect will happen to me?” t
Is inclusive of an individual's preferences, autonomy and needs, focusing on outcomes that people notice and care 2. “What are my options and what are the benefits and about such as survival, function, symptoms, and health- harms of those options?” related quality of life

3. “What can I do to improve the outcomes that are most t
Incorporates a wide variety of settings and diversity of important to me?” participants to address individual differences and barriers to implementation and dissemination 4. “How can the health care system improve my chances of achieving the outcomes I prefer?” t
Investigates (or may investigate) optimizing outcomes while addressing burden to individuals, resources, and other stakeholder perspectives

policy makers to make informed Specific to the US environment, which intervention(s) and/or decisions that will improve health PCORI recently introduced a draft product(s) is/are the best option, care at both the individual and working definition for patient- as a means of applying population- population levels.”4 centered outcomes research, as based evidence to individual care outlined in Figure 2.6 decisions t
Implies the generation and synthesis of evidence that Why are we asking these t
From a payer perspective, these compares benefits and harms of questions? data help determine the relative alternative methods of care, with a Regardless of specific methodology value of products – from both a clear intention to examine a broad and definitions, what CER, HTA clinical and economic perspective range of medical interventions and EBM do have in common is – in terms of investment of limited that they try to address fundamental resources in order to achieve the Evidence-Based Medicine (EBM) questions of how a given health care best overall health outcomes for a intervention fits into the overall population of patients t
“…the conscientious, explicit approach to care – for a patient and and judicious use of current best within a health care system overall. t
And, from an industry perspective, evidence in making decisions These are important questions for these data can help differentiate about the care of the individual all of us to answer, no matter which products and technologies based patient. It means integrating “hat” we might wear within the on key parameters of value to the individual clinical expertise system. audiences we serve with the best available external clinical evidence from systematic t
From a clinical perspective, health Issues to consider 5

COMPARATIVE EFFECTIVENESS COMPARATIVE research.” care providers and patients are As we look to evidence assessment asking for data to help determine research and evaluation methods 26 GLOBAL FORUM OCTOBER 2011

SS7-Glennie.indd 26 9/20/11 5:33 PM to contribute to the quality and There are, however, potential development of future products effectiveness of care, there are issues opportunities for all involved: and technologies. Some anticipate specific to product development that decreases in private sector should be kept in mind. t
educating stakeholders regarding investment in new technologies the complexities of the product due to lack of predictability of Obtaining stakeholder insights development process future uptake. Others cite increases early in drug development in government investments not t
gaining insights of key decision only in CER but also neglected There is recognition in major world makers early in the development disease areas, which could result in markets of the access “hurdle” process increased innovation longer term. represented by the data requirements It has been suggested that improved of HTA organizations as they make t
gaining practical and focused assessment will enhance uptake recommendations for public funding insights on health and other of effective medical interventions, of new products. Similar questions important outcomes directly the underpinning to more efficient are being raised in the US in the from payers (vs. more use of resources within the health context of CER. The PCORI research academic perspectives on data care system overall. Thus, the real scope questions noted above reflect requirements and research design challenge is to ensure that CER and the need to balance data requirements issues) HTA contribute to innovation and with the relevance of data to users help to focus R&D spending, rather (particularly patients), to ensure that t
clarity on product characteristics than stifling innovation and sending data contribute positively to patient or health/societal outcomes that research and development costs care. decision makers value, and in skyrocketing. which they have interest to invest Recently, companies like Sanofi Conclusions have announced partnerships with These same initiatives also touch Making “conclusions” on where the organizations such as Medco to gain on the issue of regulatory vs. HTA fields of HTA, CER, EBM, etc. will payer insights on clinical trial designs. review processes and whether take us in the future is premature. This arrangement also provides there are opportunities for parallel It is clear – based on the long Sanofi with information on patterns activities. There are many additional international history of comparative of drug use, to inform the generation challenges associated with this evidence assessment - that these of comparative effectiveness data to issue, most important of which concepts will not disappear from COMPARATIVE EFFECTIVENESS meet payer needs. is the need to respect the very the health care landscape. The different scientific methods and challenge will be to manage and A variety of international initiatives objectives for each of these evidence evaluate the impacts – both is tackling the issue of early input review streams. Much more intended and unintended – of these into product development, as a dialogue is needed with a broad paradigms, to ensure continued means of generating downstream range of stakeholders on this topic; innovation within the health care data relevant to multiple stakeholders however, it is clear that fairness, system as well as to the scope of (i.e., regulators, HTA organizations, transparency, and predictability will products introduced to that system. patient groups, etc.).7,8 There are be key factors in any attempts in real challenges in undertaking such this area. References activities to meet global needs, and 1. Reading the Alphabet Soup: to ensure that such input does not Impact on Innovation From EBM to HTA. O’Donnell makes studies so complex JC. DIA Global Forum (March that they can’t be executed (i.e., There are varying perspectives 2010). from a methodological or cost on the extent to which CER and 2. Luce B, Drummond M, perspective). HTA activities may impact the Jonsson B, et al. EMB, HTA,

VOL 3 ISSUE 5 GLOBAL FORUM 27

SS7-Glennie.indd 27 9/20/11 5:33 PM and CER: Clearing the London: Churchill Livingstone Confusion. Millbank Quarterly (2000) 2010;88(2):256-76. 6. http://pcori.org/pcorinput.html 3. Hailey D, et al. 2010. HTA 7. Henshall C, Mardhani-Bayne L, Agencies and Decision Makers: Frønsdal K, et al. Interactions An INAHTA guidance document. between health technology International Network of assessment, coverage, and Agencies for Health Technology regulatory processes: Emerging Assessment (INAHTA), 2010. issues, goals, and opportunities. 4. Institute of Medicine (IOM). International Journal of Consensus Report: Initial Technology Assessment in National Priorities for Health Care 2011:27 (3) Dr.D JJudithdiitht GGlennieli isiDit Director Comparative Effectiveness 8. European Healthcare Innovation Strategic Health Technology Research. Washington, DC : Leadership Network: Building a Assessment with Janssen Inc. National Academies Press, 2009. sustainable platform for multi- Canada, Co-chair of DIAís Real- 5. Sackett D, Straus S, Richardson S, stakeholder collaboration World Outcomes Task Force, and a et al. Evidence-Based Medicine: (March 4, 2011); viewed July 22, former member of DIA’s Board How to Practice and Teach EBM. 2011. ■ of Directors. COMPARATIVE EFFECTIVENESS COMPARATIVE

28 GLOBAL FORUM OCTOBER 2011

SS7-Glennie.indd 28 9/20/11 5:33 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM The Global Push for HEALTH TECHNOLOGY ASSESSMENT Potential Impacts on Innovation

Mendel Grobler, Eugene Salole

t is well known that a particular The key aspects of HTA are (i) the potential problems for the research concern of health care policy- gathering and analysis of the best and development of innovative I makers and funders worldwide clinical evidence available (preferably medicines and devices. In the case is the escalating cost of new health from randomized controlled trials), of drug development, the experience care technologies (both innovative and (ii) an assessment of cost- in HTA markets, where comparative pharmaceuticals and medical effectiveness based on the best effectiveness forms part of a cost- devices) commonly perceived to be evidence. effectiveness assessment, is that responsible for a substantial there are three broad issues that component of the escalation in HTA is now the established paradigm impact directly: technical challenges overall health care expenditure.1 This in several countries, particularly in designing studies (e.g., in order concern has led to the current those with a ‘national health service’, to minimize either false positives interest of payers in demonstrable e.g., Australia, Canada, Germany or false negatives), the impact of ‘value for money’ to underpin and the UK. In Asia too, where comparative investment decisions decisions about funding new medical several countries with socialized for innovators in diverting research technologies, and the establishment medical systems face much the funds into areas where there are of evidence-based frameworks for same health care challenges as their treatments available, and the general the assessment of value. counterparts in the west, policy- direction of medical research. ‘Comparative effectiveness research’ makers and payers are looking to (CER) is the most recent process, HTA as an appropriate framework Technical Challenges in Establishing largely US-centric 2, although it has to control expenditure, e.g., in Korea the Evidence Base been described as a component of and Thailand.4 The relatively recent There are many technical challenges ‘health technology assessment’ introduction of CER in the US has is designing clinical studies and the (HTA), the longer-established signalled the intention to embark science of study design is evolving, assessment framework.3 there, albeit in a limited way, on which means that creating an ideal a similar path to that currently evidence base that perfectly captures In its broadest definition, HTA is followed by many other markets, and quantifies a product’s relative a multidisciplinary process that where new technology is assessed efficacy and safety is not achievable. summarizes information about for comparative cost-effectiveness. For instance, designing studies where the medical, social, economic and While the US has chosen to remove the comparator is an active one is ethical issues related to the use of a the consideration of cost from CER, generally more risky than when COMPARATIVE EFFECTIVENESS health technology in a systematic, it does not preclude the use of costs placebo is the comparator - issues transparent, unbiased, robust by payer organizations (of course, include difficulties with getting the manner. Its aim is to inform the payers have been using comparative sample size right. Because active- formulation of safe, effective, health cost-effectiveness in the US for many comparator studies are usually policies that are patient focused and years prior to the implementation of initiated based on analyzing the seek to achieve best value.3 CER). comparator drug’s performance versus placebo, it is not uncommon In common usage HTA refers more However, the general trend of for the early estimates of expected narrowly to the comparative clinical encouraging or mandating the effect to be wrong, because of and economic evaluation of health comparative assessment of a incorrect power calculations for care technologies, with the objective new technology with an existing the direct comparator study. Since of providing decision-makers with comparator, while helping to the outcome from a placebo arm robust evidence upon which they answer some important questions is largely a measure of background may base funding decisions, e.g., the regarding incremental funding or statistical noise (with some reimbursement of pharmaceuticals.4 reimbursement, raises a number of exceptions), it is generally more

29

SS1-Global Push.2.indd 29 9/20/11 5:21 PM predictable; however, with an active fiduciary responsibility, including differences between compounds, comparator the magnitude of the the assessment of future returns on such as those arising from differences clinical difference that is expected the investment made. Investment in formulation, dosage schedule, to be achieved is very likely to be decisions apply decision rules, e.g., etc., on compliance. Since price is smaller, and, therefore the patient the capital asset pricing model6, and the outcome of HTA assessment numbers required will generally require a positive financial return systems, it becomes the incentive (or be much higher than would be for investors. Therefore investment lack thereof) that guides the future of necessary for a placebo-controlled will be channelled into areas that research investment by the industry study. The alternative is to rely on at least meet historic firm or sector into improvements and innovation indirect comparisons – but these financial performance. Consequently, in medical technologies. The have greater uncertainty and are in addition to investments in incentive for incremental product less likely to accurately quantify comparator-controlled studies being enhancement, a necessary feature of differences in efficacy, let alone the significantly higher than for placebo- medical innovation, is compromised, safety, of test compounds. controlled ones, the prices paid for and this impacts the entire industry, new technologies are generally lower, including generic manufacturers, Similar technical difficulties a critical emerging factor in the on- particularly those seeking to become also apply to the acquisition of going cycle of investment. innovators themselves. evidence for medical devices. This heterogeneous group of medical Of more concern to society is that Impact on the General Direction of technologies presents a wide range of the prices determined through HTA Medical Research challenges from an HTA perspective, and comparative cost-effectiveness Lastly, a broad consideration is the chief amongst which is the relevance are unlikely to be efficient ones. impact of comparative effectiveness of data acquired in an environment The most common economic and cost-effectiveness on the general where rapid incremental innovations evaluation method in HTA is where trend of innovation in medical in technology result in product life- the incremental costs and benefits technology. Some companies are cycles as short as a few months. Of of a new product are compared with already assessing their pipeline course, surgically-implanted devices existing alternatives in the form of through the lens of HTA, not just for like cardioverter-defibrillators and an incremental cost-effectiveness probability of technical success, but prosthetic hips, whose true value ratio (ICER). HTA authorities may for commercial success based upon may not be realized for years, apply global or category-specific the comparative effectiveness of the bring their own set of assessment thresholds to the ICER, so that anticipated product profile.8 The challenges. technologies with ratios above it higher cost and risk of comparative are denied subsidy and those below research may force companies out Impact on Investment Decisions for threshold are approved. However, of areas of unmet need where the Innovation it can be shown that applying fixed return is no longer commercially The above technical issues or constant cost-effectiveness justifiable. If this redirection is too compound a commercial issue. thresholds has a detrimental effect early, i.e., there is disinvestment The future availability of improved on price-setting in the long run – prior to the achievement of adequate health care products, such as drugs and more importantly, over time, technical success (i.e., reaching the and medical devices, requires results in market failure.7 As a result, point at which there is no more need research-based manufacturers to research-based manufacturers are for innovation in the therapeutic invest required capital to develop likely to choose to invest funds in area), then there is a loss to society. innovative health care technologies areas away from what society needs. In some therapeutic areas where for the future. In private markets there is a long gap between the the utilization of shareholder Lastly, HTA systems, as currently launch of new products, and during funds is subject to standards of practiced, are unable to detect minor which prices of comparator products COMPARATIVE EFFECTIVENESS COMPARATIVE

30 GLOBAL FORUM OCTOBER 2011

SS1-Global Push.2.indd 30 9/20/11 5:21 PM decline significantly, innovation expenditure in the EU. European on Health Economics; Toronto, may cease very early indeed, as Economy. Economic Papers. 400. Canada, July 10-13, 2011. illustrated by the aminoglycoside Brussels: European Commission; antibiotics. On the other hand, 2010. 8. Berger ML, Grainger D. comparative effectiveness and Comparative effectiveness cost-effectiveness may also lead 2. Neumann PJ, Lin P-J, Hughes research. The view from a to a greater focus on those under- TE. US FDA Modernization Act, pharmaceutical company. researched therapeutic areas Section 114. Uses, Opportunities Pharmacoecon. 2010; where there are no comparator and Implications for Comparative 28(10):915-922. ■ products yet available – and this, of Effectiveness Research. course, will benefit society. So the Pharmacoecon. 2011; global push towards comparative 29(8):687-692. effectiveness and cost-effectiveness may potentially be a benefit to the 3. EUnetHTA. HTA Definition. community, albeit an unplanned one. EUnetHTA web site. http:// www.eunethta.eu/Public/About_ HTA can be an excellent tool to EUnetHTA/HTA/. Accessed help make explicit the issues and August 15, 2011. parameters to be considered in making decisions about funding 4. Department of Health & Ageing. medical technology, but applied PBAC Guidelines. Australian slavishly, without due regard to Government web site. http:// the value of innovation to www.pbs.gov.au/info/industry/ Mendel Grobler, MBS improvements in health care listing/elements/pbac-guidelines. itself, and the appropriateness of Accessed August 15, 2011. a reasonable financial return to suppliers, it can undermine the 5. Jirawattanapisal T, Kingkaew P, objective of helping patients in Lee T-J, Yang M-C. Evidence- need. The current period represents based decision-making in Asia- a key moment in the evolution Pacific with rapidly changing of HTA: where if it survives (or health-care systems: Thailand, suppliers survive it), it will mature South Korea and Taiwan. Value COMPARATIVE EFFECTIVENESS into a process that not only Health. 2009;12(suppl 3):S4-S11. considers purchasing efficiency to be its primary purpose, but also 6. Fama EF, French KR. The capital considers its equally important role asset pricing model: theory in informing the future supply of and evidence. J Econ Perspect. Eugene Salole, PhD innovative medical technologies. 2004;18(3):25-46. The authors, Mendel Grobler, MBS Disclaimer 7. Grobler M. Health technology and Eugene Salole, PhD are employed The views expressed in this article assessment: longitudinal impact of at Patient Access, Pfizer Australia, are those of the authors alone. fixed cost-effectiveness thresholds Sydney, Australia and can be reached and comparator prices changes at Patient Access, Pfizer Australia, References on the market. Poster presented 38-42 Wharf Road, West Ryde, NSW 1. Dybczak K, Przywar B. The role at: Transforming Health & 2114, Australia; eugene.salole@ of technology in health care Economics. 8th World Congress pfizer.com.

VOL 3 ISSUE 5 GLOBAL FORUM 31

SS1-Global Push.2.indd 31 9/20/11 5:21 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 MANAGING Is Conditional the Future of

Wills Hughes-Wilson Ana Palma

Introduction and for which increasingly complex challenge. When data is scarce, n a fast-changing world, data sets are being presented. which is increasingly true at the withw national budgets time of marketing authorization, I underu increasing pressure, The issue reaches even larger each country finds its own way to governmentsgo er struggle with proportions when it comes to address the uncertainty. On top of maximizing health service provision orphan drugs used to treat rare that, the EU’s pharmaceutical system to a fast-growing and aging patient diseases: regulators need data to has multiple parties and players population, while remaining within assess the products; but, at the time – including Member States, the the limits of available resources. of marketing authorization, data is European Commission and European Having medicines that are safe, scarce. The nature of orphan drugs Medicines Agency – as well as other high-quality and efficacious is often means that there is a real, serious, stakeholders, such as users and no longer enough in this context. often life-threatening unmet medical providers of health care, that all have Treatments also need to be cost need, often with no alternative to work with what is already in place, effective, or reimbursed patient treatment. In such a context, the focusing not only on what has to be access will be denied. Governments medical need drives the risk-benefit done but also what can be done. and payers are increasingly looking analysis, and timely decisions on to Health Technology Assessment marketing authorization are taken It is acknowledged among Member (HTA) methodologies in an attempt on the basis of data sets that very States that there is a need to avoid to understand and evaluate the real often do not answer, or do not fit, duplication of efforts in developing added value of drugs. This is true the Member States’ needs. Such a HTA capabilities. This is crucial to in Europe, but equally elsewhere – situation where uncertainty is high, maximize the efficiency of post- HTA and Comparative Effectiveness but the need is great, requires an marketing authorization follow-up Research (CER) represent a global increased flexibility from decision- and to provide transparency in how trend that is here to stay. makers at all stages of the process. it is achieved. All involved parties This challenge is set to expand will have to be engaged, flexible and Current regulatory systems in Europe into many more areas of drug willing to share information. The are highly developed to demonstrate development, as the technology and HTA concepts need, therefore, to be quality, safety and efficacy, and our application of it advances. brought into the product life-cycle as grant a regulatory marketing early as possible to reduce uncertainty authorization on a risk-benefit basis. These hurdles and the changing at the time of marketing authorization But clinical practice often gives rise environment for drug development and, ultimately, reimbursement. to different outcomes, as several and availability have been the subject examples have shown over recent of several DIA workshops in recent Another challenge is that years. Furthermore, Member States years, including dedicated Tracks/ governments and HTA agencies/ increasingly want to understand what Themes at the DIA EuroMeetings payers want to understand what happens when a drug goes outside and two specific HTA Forum they are paying for, which is not the double-blind randomized clinical workshops, in 2009 and 2010. always easy to demonstrate at the trial setting into a “real-life” context. These conversations provided the time of marketing authorization, In addition, as technology allows us opportunity for drug developers, especially in the context of orphan to advance into areas of treating high regulators, HTA bodies and payers to drugs. Clinical trials are, by necessity, unmet medical need, the risk-benefit examine potential ways forward. small. This stems firstly from most equilibrium may give a result that patients remaining undiagnosed until answers the regulatory question, but The Challenges and Concerns a treatment is available, and secondly does not answer the payers’ needs. In Europe, each country has its own from the flexibility required by the

COMPARATIVE EFFECTIVENESS COMPARATIVE Finally, regulators face assessments way of approaching HTA, which risk-benefit system of approvals of therapies of increasing complexity, makes a harmonized approach a that might mean that a drug is 32

SS6-Wilson.indd 32 9/20/11 5:30 PM INCREASING UNCERTAINTY: Reimbursement with Evidence Development Sustainable Health Care Systems?

approved early with a small data being debated and developed. access to orphan drugs and make set against a background of a high These aim at creating a system that access more equitable. It finds and urgent unmet medical need. As for conditional reimbursement its roots in the conclusions of the a result, there is often not a great against in-life evidence collection, High Level Pharmaceutical Forum, understanding of the true benefit which is based on collaboration dating back to October 2008. These of the product in life. This makes between EU Member States. It is conclusions highlighted the need for governments wary of allocating their worth mentioning that although taxpayers’ money. the drugs in this “laboratory” are t
early dialogue between companies scheduled to be orphan drugs, the and pricing and reimbursement The heterogeneity between regulators proposals for implementation cover authorities and HTA agencies payers is another the possibility of expanding such concern in the overall context, a system of managing uncertainty t
exchange of knowledge amongst mainly their difference in judgment to other, non-orphan drugs in the Member States and European of significance of value. That is why future. Furthermore, since non-EU authorities on the scientific collaboration between these two countries are involved in several assessment of the clinical added parties has been identified as one of the projects as observers and value of orphan drugs of the keys to success in managing participants, these initiatives could uncertainty and in bringing better have a wide-ranging impact in t
promotion of the initial uptake drugs to the market faster. the field of pharmaceuticals, well of orphan medicines through beyond the purely orphan or purely conditional pricing and The fact that, on the other hand, European arenas. reimbursement decisions there is an increasing patient population, keen to get access The “CAVOD” Principles t
building of EU-level awareness and to innovative, effective, timely One of the initiatives recognized expertise on orphan diseases treatments, makes this dilemma as a promising avenue to explore one where uncertainty needs to be in addressing the challenge of It remains to be seen if these keys to managed with a great amount of uncertainty experienced at the managing uncertainty can be turned flexibility and urgency. time of marketing authorization for into reality. orphan drugs is the proposed system of “Clinical Added Value of Orphan

Possible Solutions Harmonization of Two Worlds: COMPARATIVE EFFECTIVENESS In sum, everybody recognizes each Drugs” (CAVOD). Its aim is to Regulatory and HTA other’s concerns, particularly in the acknowledge the legitimate questions The heterogeneity between orphan drugs space, where such from governments to understand regulators and HTA agencies/ dialogue has been advanced as a the value, role and contribution of payers has been highlighted in this solution as early as the 2005-2008 the proposed orphan drug, while article as another concern for those High Level Pharmaceutical Forum. not holding up patient access to operating in this uncertain context. What is needed now is to reach out treatments while the information But is it possible to merge the two openly to all parties, even if some is found. The vision behind it worlds? Can the regulatory review of these are not (yet) experts in the is that it would allow European for marketing authorization and the rare disease arena, to sit together, countries to cooperate on pooling HTA assessment for reimbursement and to try to understand each other’s the information on orphan drugs, be harmonized to facilitate a bridge concerns (and what drives them) in a to allow them to make informed to patients? constructive way. decisions on the basis of the most up-to-date and comprehensive Some regulators have argued that In the orphan drug context, there information possible. The ultimate the main barrier to increased are several initiatives currently goal of this system is to accelerate collaboration is simply a difference

VOL 3 ISSUE 5 GLOBAL FORUM 33

SS6-Wilson.indd 33 9/20/11 5:30 PM in culture. The debate on evidence information), and argue that the technology needs to be developed, requirements is mostly about traditional way of introducing assessed, reimbursed and delivered. endpoints and it has been suggested drugs into the market has come to The patient is viewed by all the other that, for example, what is needed an end. The typical client-provider parties not only as a key participant is better methodologies for relationship is no longer enough in the process, but also as having indirect comparisons as opposed for the sustainability of the health priceless insight on key scientific to “a gigantic study with the same care system. It requires a strong areas such as benefit-risk and value comparator”. Where language is partnership between companies and assessments, and in discussions concerned, a simple understanding health administrators. about how to capture patient of the terminology could help – what reported outcomes (PRO). The HTA agencies/payers call “Managed Industry has expressed support questions mostly center on the Entry Schemes,” regulators express as for advanced dialogue between right methodology to capture the “progressive (provisional) licensing/ regulators and HTA agencies/ patient’s feedback and outcomes, authorization” – and, thus, the payers, particularly with regard to and how to translate it into differences are often perceived to clinical endpoints. And, while there information that can be used be greater than they are; both are is a divergent decision on “clinical effectively in other parts of the essentially similar and could evolve benefit” between HTA agencies/ decision-making process. into alignment. payers, some trends in alignment are already being observed: HTA The need to have the patients at Some HTA agencies/payers have agencies/payers are increasingly the center of every stage of the argued that while regulators cooperating with and getting process is even more acute in the influence them, HTA agencies/payers closer to regulators. In the eyes of field of rare diseases and orphan do not influence regulators, but the industry, these trends could drugs – often the largest source of they should. HTA agencies/payers represent an opportunity not only expertise is those who are living with have acknowledged the differences to accelerate access to innovative the condition in question, either as between them and regulators, while treatments to more patients, but also patients themselves or as families at the same time recognizing that to foster valuable innovation. or caregivers. Indeed, patients both can benefit from being better have intervened in the debates on connected. For example, HTA can The EU has universal health care guidance on a risk-benefit analysis, be based on science, so it could systems, based on solidarity, and pointing out that they are already probably be merged with regulators’ improvements in public health living in an unsafe world and so a processes, which are also science are a societal goal. In this context, little risk from a treatment does not based. both communities – regulators and worry them. HTA agencies/payers – ought to Agencies already acknowledge enable those who develop valuable The Future? the need for more EU dialogue innovative drugs to treat patients. It is clear that early, open and strong in pricing and reimbursement Industry is increasingly required to collaboration between all parties processes and discussions, the think ahead, to identify – or be told involved will be absolutely vital when need for closer collaboration clearly – what will be valued, and to dealing with the challenges described between all stakeholders, and a anticipate evidence requirements above. This is particularly true in tighter relationship between payers throughout the product lifecycle. the field of orphan drugs, where the and regulators for better data- diseases and patients treated are sharing. HTA agencies defend a The Patient at the Center rare, but so is the expertise required mindset switch from expenditure At the center of this whole debate is, to develop drugs, to diagnose and to

COMPARATIVE EFFECTIVENESS COMPARATIVE to investment (outcomes-based of course, the patient – for whom the treat them.

34 GLOBAL FORUM OCTOBER 2011

SS6-Wilson.indd 34 9/20/11 5:30 PM Only continued collaboration between governments, regulators, HTA bodies, payers, health care providers and patients will ensure successful achievement of the objectives of a health care system. Partnership, open dialogue and understanding will continue to be key in defining what a system will need to look like to meet the requirements of all decision makers, and to provide insight into how to Wills Hughes-Wilson is the Ana Palma is the Manager, Health manage increasing uncertainty. ■ Vice-President, Health Policy Policy Europe at Genzyme. Europe at Genzyme. COMPARATIVE EFFECTIVENESS

VOL 3 ISSUE 5 GLOBAL FORUM 35

SS6-Wilson.indd 35 9/20/11 5:30 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 The Role of LEGISLATIVE MANDATES in CER and Drug Development

William D. Marder

ecent federal legislation prescribers in the 1960’s have wanted 1962 FDA amendments changed included substantial funding a CER study to guide their behavior? the timing pretty dramatically.2 We R for comparative effectiveness I think the answer is clearly yes. avoid issues like the birth defects research (CER). The same legislation But they didn’t get anything like caused by thalidomide, but do so by also included incentives for the that. Why not? Probably no one raising the cost of developing new adoption of electronic medical wanted an answer badly enough to drugs and delaying their entry into records (EMR) and health fund a structured study. Instead, the market. Higher income societies information exchanges (HIE). This prescribers relied on the experience have a greater demand for product essay explores the important in their practices, stories from their reliability. interactions between health colleagues, and case reports in the information technology and CER. literature. Although they did receive If the income story is clear, the Special attention will be paid to the visits from pharmaceutical company “price” story is not. The relevant impact on drug development. representatives, they didn’t have price concept is related to the cost patients armed with the latest online of getting answers to questions. First, let’s consider some history from news or information from direct-to- CER in the US is not mandated for the Wikipedia article on Librium. consumer ads. entry into the market. In fact, the “Chlordiazepoxide was the first enabling legislation limits the scope benzodiazepine to be synthesized Why, 50 years after the introduction of government-funded CER to avoid in the mid-1950s. Chlordiazepoxide of Valium, are we entertaining the considerations of cost and mandated was synthesized from work on a idea of funding comparative studies? coverage. CER is intended to chemical dye, quinazolone-3-oxides. Put differently, what is the cause of convince providers and patients, not It was discovered by accident when the delay? A potential answer can be compel behavior. Even with these in 1957 tests revealed that the generated by applying the tools of limits, CER may still have important compound had hypnotic, anxiolytic, economics to look at the economics effects by influencing payer and muscle-relaxant effects. Three of CER. Economics is a social decisions, especially private payers years later, chlordiazepoxide science that focuses on the roles of who are not limited in the same was marketed as a therapeutic income and prices as determinants way as government. Payers, as they benzodiazepine medication under of behavior. Both income and prices make coverage and reimbursement the brand name Librium. Following play important roles in explaining the decisions, have many treatments chlordiazepoxide in 1963, diazepam timing of our desire for CER. whose comparative effectiveness hit the market under the brand name they would like to understand. If Valium followed by many further The income story is clear. Over the payer decisions are going to be benzodiazepine compounds, which past 50 years, per capita income guided by the results of CER, the were introduced over the subsequent in the US has grown dramatically. cost of completing a CER study is years and decades.1” We are much richer today than going to be as relevant as the cost of we’ve ever been. Richer societies completing Phase III trials for market The world has really changed. Three can afford more reliable answers to entry. years from discovery to launch– that important clinical questions. It was is pretty fast. As this article focuses possible 50 years ago to proceed What are the costs of conducting more on the Valium question than from discovery to product launch CER? The answer will depend on the introduction of the new class in three years. That had some real the nature of the study undertaken. of drugs, the question is, “Wouldn’t benefits for the population 50 years There are three broad classes of CER physicians getting ready to prescribe ago. New drugs were brought to studies: randomized controlled trials the newly introduced Valium want market much more quickly, but (RCTs), prospective observational

COMPARATIVE EFFECTIVENESS COMPARATIVE an answer to the question, ‘Is this the risks associated with those new studies (including registry studies), a me-too’ drug?” That is, would drugs were not well understood. The and retrospective database studies. 36

SS2-Marder.2.indd 36 9/20/11 5:23 PM They are listed in descending order providers are the most expensive they will lower the cost of of cost. RCTs are quite expensive. studies, e.g., RCTs. prospective observational studies They include all of the data collection and retrospective database studies, costs of a prospective observational Phase III trials are the classic RCT. studies not held in as high regard by study plus all of the costs associated They are among the most expensive providers. These new information with experimenting on human elements in the drug development technologies will have a much beings (human experiments process. CER clinical trials can be less important impact on the cost raise ethical issues that must be even more expensive. Most phase of answers from RCTs. The cost carefully reviewed and revealed to III trials are placebo-controlled. For comparison is easy between RCTs participants to gain truly informed a CER study, the comparison group and prospective observational consent). Prospective observational has to be chosen carefully and there studies. All of the cost savings from studies share many of the same may be multiple comparison groups. new information technology in a costs as RCTs. They incur all the Clearly, with multiple groups the prospective observational study custom data collection costs (e.g., price of an answer is higher than will be observed in the RCT. Health patient surveys, medical record with a single comparison. But even information technology will have no abstraction), but these studies save with a single comparator, there’s a impact on the other costs of the RCT, on the randomization components way in which the CER study has a such as the randomization and the characteristic of RCTs that have higher expected cost. It is difficult ethical treatment of subjects that are ethical implications. Registry studies to choose the right comparator. so important when experimenting on have similar cost structures to stand- Also, CER clinical trials take a long people. alone prospective observational time. The likely competitor in the studies, but a single registry can year when the trial is designed may In summary, the stimulus bill and spread those costs over multiple be obsolete by the time the trial is health care reform added billions of studies. Finally, retrospective done. An obsolete comparator can dollars in funding to answer basic database studies have the lowest mean a not very useful study in the questions about which treatments costs. The data in retrospective end. And, in the event that drug are more effective than others in studies have been collected for developers believe that a CER study the real world. Getting answers to a different purpose; thus, data is desirable prior to drug launch, the collection costs are appropriately cost of drug development will be that those questions will be expensive for allocated outside the study. Only the much higher. two reasons. First, there are a lot of COMPARATIVE EFFECTIVENESS analysis costs are relevant. Analysis questions to answer. Second, there costs are roughly the same across If provider expectations continue seems to be resistance to generating each type of study. to value RCTs above other study affordable answers based on the bias types, this will inevitably drive up the toward RCTs and the reluctance The answer to any CER question will expected cost of CER answers and to seriously consider retrospective also depend on how the question is we will only be able to ask a limited database studies. Potentially framed – what is being compared number of questions. This is where offsetting that resistance is federal to which alternative(s), and which mandated and incented adoption funding and mandates for adoption patient groups are being compared. of EMRs and other advanced health of new information technologies. The cost of the answer will depend information technology may be In addition to their clear ability on the method used for the study. very important in the widespread to improve quality of clinical care From the perspective of the sheer development and use of CER. simply by making information quantity of answers we would like available at the point of care, they from CER, it is unfortunate that the Electronic medical records and also will provide the raw material kinds of studies that traditionally HIE have the potential to lower the for more affordable answers to CER have been most persuasive to cost of an answer. Unfortunately, questions.

VOL 3 ISSUE 5 GLOBAL FORUM 37

SS2-Marder.2.indd 37 9/20/11 5:23 PM The question remains–how do less H. Roth (January 15, 1996) (in expensive, yet scientifically rigorous, Eng). The Complete Story of the observational studies (including Benzodiazepines (seventh ed.). retrospective ones) attain the clout of USA: Oxford University Press. RCTs with decision-makers in order ISBN 0195103998. Accessed 7 Apr for us to gain more CER answers 2008. rather than fewer at a price we are willing to pay to get those answers? 2. Peltzman, S. An Evaluation of References Consumer Protection Legislation: 1. Wikipedia article on The 1962 Drug Amendments, William DD. MMarder,arder PhDD, is Chlordiazepoxide referenced Journal of Political Economy, Vol. employed by SVP Analytical June 30, 2011 citing Cooper, 81, No. 5 (Sep. - Oct., 1973), pp. Consulting & Research Services, Jack R; Floyd E. Bloom, Robert 1049-1091 ■ Healthcare at Thomson Reuters. COMPARATIVE EFFECTIVENESS COMPARATIVE

38 GLOBAL FORUM OCTOBER 2011

SS2-Marder.2.indd 38 9/20/11 5:24 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM The Effect of COMPARATIVE EFFECTIVENESS RESEARCH on Drug Discovery

Richard K. Harrison

rug discovery is an annum has remained reasonably documents used to validate and inherently difficult process. constant over the last twenty years, start clinical trials. Companies D It currently takes between the amount of money invested in are already beginning to review twelve and seventeen years to deliver R&D has continued to rise [Figure 1]. early- and mid-stage development new medicines. Presently, new While the number of NCEs launched pipelines with an unprecedented compounds must show they are safe, each year continues to remain level of reimbursement scrutiny. efficacious and have a positive relatively constant, the time to take This has resulted in potentially benefit-to-risk ratio. Comparative them to market has been increasing. non-reimbursable projects being Effectiveness Research (CER) The consequence of these two factors terminated earlier in development. initiatives will add the burden of results in an average cost per launch product reimbursement, which has that has been currently estimated as Early clinical trials will be as much been termed the “fourth hurdle of high as 3 billion USD. 6 about efficacy as they are about drug development.” 4 Think of it as safety. Translational medicine the need to persuade someone to pay How will the requirements of CER will dominate the early phases as a fair price for the treatment. affect drug discovery? In its current companies will look for efficacy Reimbursements must be in the paradigm the requirements will no readouts in humans instead of relying forefront of everyone’s mind, from doubt increase the time and cost to on animal models as predictors of preclinical to post-marketing. The market, and result in additional late- human behavior. Biomarkers will be burden sounds simple: “The stage clinical failures. A retrospective assessed to insure mechanisms are generation and synthesis of evidence analysis of Phase III failures between correct. Both of these changes have that compares the benefits and 2007 and 2010 revealed that of the been put in place to reduce late-stage harms of alternative methods to 83 failures, over 60% were found costly failures, and time will tell if prevent, diagnose, treat, and monitor to be no better than placebo.1 The these changes have been successful a clinical condition to improve the added burden of superiority will no in reducing attrition. delivery of care.” 5 doubt increase this failure rate unless fundamental changes take place Trial designs will also change. To The implications are enormous. in the industry; these changes are be sure compounds are showing No longer can you be second or beginning to take shape. superior efficacy, clinicians will be third to market and expect to looking for those patients who have gain the 20% to 30% market share The changes have begun in pre- the best chances of responding to COMPARATIVE EFFECTIVENESS historically provided for drugs for clinical research. Company the medicines. Patient stratification new indications. The days of multiple mentalities will have to switch from or personalized medicine, where the blockbuster compounds for a given producing “what we can make” to use of genetic information to identify indication being approved while “what we can sell.” 3 Scientists now the best responders, insures the right showing only marginal increases in routinely compare their research medicines will be getting to the right safety and efficacy are over. relative to the competition to access genetically predisposed individuals. if they can be the first to market The gold standard for determination This increased burden does come and show superior efficacy. This is of comparative safety and efficacy of at a good time. According to CMR a difficult task due to the secretive therapeutic interventions remains International despite the high nature of drug discovery, and has the randomized controlled clinical investment in R&D (up to 20% of lead to a new era of cooperatively trial (RCT). The main advantage is revenues by major pharmaceutical between companies. that this approach, through proper companies) the industry is currently bias control, can reliably detect facing unprecedented challenges Evidence-based effectiveness and quantify small differences to its R&D productivity. Although evaluations and real world outcomes that are beyond the resolution the number of NDAs approved per must be built into the supporting of observational methods. It is, 39

SS3-Harrison.indd 39 9/20/11 5:26 PM R&D expenditure Development times NME output Sales

275

250

225

200

175

150

125

INDEXED TO 1999 100 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009* 75 50 Figure 1. The trend in sales, cycle time, expenditure 25 and NME output for a cohort of 40 pharmaceutical 0 YEAR companies over the last ten years.

therefore, neither surprising nor and has a vision for a technology- Phase Iii and Submission Failures: coincidental that the FDA generally enabled, communication-based 2007-2010.” Nature Reviews Drug requires replicated RCTs as the health care system that considers Discovery 10.2 (2011): 1-1. Print. evidentiary standard to support patients both partners and leaders 2. Conner, Steve. “Glaxo Chief: comparative promotional claims. in their own care. 7 Our Drugs Don’t Work on Moat However, RCTs are considerably People.” The Independent 2003, more costly than observational As mentioned earlier, one positive December8 ed., sec. Science. approaches, the time to getting change this has brought about is Print. an answer is invariably longer, the spirit of cooperation between 3. Harrison, R.K, et al. “Healthcare the general nature is frequently organizations. A greater willingness Reform Is a Global Issue.” questioned, and no single trial to share risk and share reward PharmaTimes (2011). Print. can ever be designed to answer all has been seen in the industry. Pre- 4. Honig, P. K. “Comparative relevant clinical questions. 4 competitive collaborations Effectiveness: The Fourth Hurdle are becoming “business as usual” in Drug Development and a Role Not all the changes will have a in order to share cost and risk in for Clinical Pharmacology.” Clinical negative impact on drug discovery. drug discovery. Some examples Pharmacology & Therapeutics 89.2 The results should be better include the Lilly Phenotypic (2011): 151-56. Print. medications that will be effective Drug Discovery Initiative (PD2), 5. Medicine, Institute of. “Initial to a larger population of those the SAE consortium, The National Priorities for taking it. Allen Roses, worldwide Biomarkers Consortium, and Comparative Effectiveness vice-president of genetics at the Alzheimer’s Disease Research “ (2009). GlaxoSmithKline (GSK), said fewer Neuroimaging Pharma/NIH. 6. Munos, B. “Lessons from 60 Years than half of the patients prescribed of Pharmaceutical Innovation.” some of the most expensive drugs In addition, companies continue Nature Reviews Drug Discovery actually derived any benefit from to develop and market programs 8.12 (2009): 959-68. Print. them. The vast majority of drugs - jointly. Some examples include 7. Versel, Neil. “Patient Advocates more than 90% - only work in 30 or Collaborations Pfizer/BMS co- Want More Say in Health Care.” 50% of the people”. 2 Greater success developed apixiban, Bayer/J&J Information Week (2011). ■ rates for greater numbers of people rivaroxaban approved in EU, and will have advantages that cannot be BMS/AZ saxagliptin approved in measured. the US in 2009.

One additional advantage is that The effects of the CER initiatives patients will have a greater say in on drug discovery will not be the medicines they take. The need known for years. At the least, to develop medicines that meet this effort should mean greater the needs of payers will increase medicine for patients, greater value pressure on pharmaceutical R&D for your health care dollars, and organizations to work in partnership a renewed spirit of cooperation with external organizations, between companies. Any one of including patient advocacy groups. these successes is well worth the A coalition of consumer, labor, and efforts. patient advocacy groups called Richard K. Harrison, PhD, is the consumers “the most significant References Scientific Director, Life Sciences at

COMPARATIVE EFFECTIVENESS COMPARATIVE untapped resource” in health care, 1. Arrowsmith, J. “Trial Watch Thomson Reuters.

40 GLOBAL FORUM OCTOBER 2011

SS3-Harrison.indd 40 9/20/11 5:26 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

Role of OBSERVATIONAL RESEARCH in CER

Richard Gliklich

s regulators and payers a therapy in a tiered formulary Broadly speaking, the available seekse to reduce risks or may need different evidence than a armamentarium of approaches in A healthh care spending, and regulator evaluating the benefit to CER include synthesis activities physiciansph sicians and patients look for risk profile of a product, or a patient (such as systematic reviews of improved and more personalized choosing a therapeutic option for existing evidence and meta- care, the discussions on comparative his/her illness. analyses), experimental trials effectiveness research (CER) and the (i.e., randomized controlled appropriate methods for conducting The issue of what information trials), and non-experimental CER are heating up. the decision maker needs is studies, such as observational complex and still poorly defined, studies. But, the specifics of how Effectiveness research is not and therefore, CER is perceived to select an approach for a given new. Over the past few decades, by manufacturers as inherently situation are fuzzy. In forming effectiveness research has been part costly. Recent decisions have only the Patient Centered Outcomes of health technology assessment, added to this angst. For example Research Institute (PCORI), the outcomes research and evidence- in 2008, Vanda Pharmaceuticals US government reached the same based medicine. The ‘newness’ received a not-approvable letter for conclusion as it required PCORI of CER or now ‘patient-centered Iloperidone from the US Food and to develop a Methods Committee outcomes research’ is based more on Drug Administration (FDA) because to help guide decision makers and the audience than the methods. CER they did not demonstrate that the researchers in understanding what focuses on the informational needs drug was any more effective than a types of studies are appropriate for of decision makers who must make competing product. The Center for different types of questions. But even decisions ranging from policy and Medicare and Medicaid Services this guidance will only be part of payment to clinical care. (CMS) made a national non-coverage the solution. Assuming that there is determination for CT colonography not one single best answer for every If CER is about decision makers, because, while the trials presented question, those who invest precious then the choice of research approach were strongly supportive and other research dollars will need processes should be focused on several health plans already offered coverage in place that consider not only the things such as: the decision itself, for the procedure, the data provided value of the information that can be the existing level of evidence for was not considered generalizable to derived from different approaches, the particular question in that the Medicare population. As stated but also how costly and timely that COMPARATIVE EFFECTIVENESS condition, and the relative needs and in the draft coverage determination, evidence generation will be for preferences of the decision maker. A “The applicability of the results of a specific decisions. decision has similarities to a research study to other populations, settings, question, but it is not the same. A treatment regimens and outcomes In light of this consideration, decision weighs alternatives, each assessed is known as external what is observational research with imperfect information, to make validity. Even well-designed and and what is its likely role in CER? a timely determination using best well-conducted trials may not supply Observational research has been available evidence fit for the purpose. the evidence needed if the results defined as ‘research not involving The level of, or gaps in, evidence of a study are not applicable to the direct intervention on human beings’. for the question in the particular Medicare population. Evidence that In observational studies, cohorts condition drives what information provides accurate information about or groups of patients are generally is still needed. A third consideration a population or setting not well defined by their exposures, such is the perspective and evidence represented in the Medicare program as diseases, products, procedures, preferences of the decision maker. would be considered but would suffer or health care services. The terms A payer determining the place of from limited generalizability.1” ‘prospective’ and ‘retrospective’

41

SS4-Gliklich.indd 41 9/20/11 5:28 PM depend on when the outcome of Unlike most RCTs, observational populations (e.g., pregnant women interest occurs in relation to the studies can provide a ‘real-world’ and children). This was the case in start of the research. In prospective view of how a product is actually the CT colonography example cited studies, the outcome occurs after being prescribed by a physician and above. the research has started, while if used by a patient. Theoretically, their the outcome had already occurred inclusion criteria are broader and Applicability when the research began, it would be exclusions more limited allowing Since RCTs dictate treatment by considered ‘retrospective’.2 a more diverse population to be protocol and generally evaluate studied. Four potential advantages results based on the treatment Randomized controlled trials of observational CER for certain that was intended rather than the decisions can be thought of one actually used, they may not (RCT) are and will remain the from the perspectives of reality, be applicable to answering certain standard for regulatory product generalizability, applicability and questions. If a patient is randomized approval. Treatment is assigned by availability. to drug or procedure X but does not randomization and clinician behavior take or receive it, it would not be is largely driven by protocol. These Reality reasonable to consider a subsequent studies have strong internal validity, The ‘real world’ view provided by result or adverse event as attributable meaning they are believed to be observational research can be quite to that drug or procedure. For providing significant truth about different than randomized trials. example, in the Spine Patient the population that is studied. For example, one study compared Outcomes Research Trial (SPORT) Experimental approaches have long Medicare mortality rates for carotid 66% of those randomized to receive been considered to be the gold endarterectomy (CEA) to the pivotal surgery received it by four years standard and the least biased method trials results that had established whereas 54% of those randomized to of conducting research, and to the safety of the procedure and receive non-operative care received some extent that thinking has been concluded that “Medicare patients’ surgery by four years.4 Further, if the extended to CER. However, these perioperative mortality following decision maker’s question is one for same experimental approaches have CEA is substantially higher than that which physician behavior is actually been considered limited by factors reported in the trials, even in those being studied, then an RCT might such as: being performed in settings institutions that participated not be a useful approach at all. that are not typically reflective of the in the randomized studies. Caution real-world (i.e., specialized research is advised in translating the efficacy Availability sites); dictating treatment by protocol of carefully controlled studies of Even if an RCT is the right CEA to effectiveness in everyday methodology, there are more rather than clinician decisions; practice.” 3 questions than can possibly be focusing on narrowly defined study answered with RCTs alone. Other populations; and analyzing data by Generalizability approaches that will be ‘fit for how the product was intended to One of the key limitations of RCTs is purpose’ must be considered. For be used and not how it was in fact that the population that is accessible example, while most patients admitted used. Sir Michael Rawlins, Chair to the investigator and willing to be with acute exacerbations of chronic of the National Institute for Health randomized may not be reflective of obstructive pulmonary disease and Clinical Excellence (NICE) the full population of interest (the (COPD) are treated with high dose in the United Kingdom famously target population). As such, it is intravenous (IV) steroids rather than stated that randomized trials have difficult to draw conclusions about lower dose oral steroids, no definitive been placed on ‘an undeserved those patients who were not studied study has demonstrated a clear pedestal’ with respect to the accepted such as older, younger, ethnically advantage of the IV route. A large

COMPARATIVE EFFECTIVENESS COMPARATIVE hierarchies of evidence. diverse, or more vulnerable observational study of 84,000 patients

42 GLOBAL FORUM OCTOBER 2011

SS4-Gliklich.indd 42 9/20/11 5:28 PM clearly showed that the high dose IV effectiveness research and using key determinant in the evidence approach was not more effective, but observational studies as one weighting that a particular study potentially more risky and costly than method to collect and report on the should receive.9 In 2007, the Agency the oral approach, leading to a change data. In 2010, WellPoint revealed for Healthcare Research and in treatment guidelines. An RCT to standardized CER guidelines, “Use of Quality (AHRQ) funded a landmark evaluate the same issue would have Comparative Effectiveness Research federal initiative to develop a guide required more than 30,000 patients at and Observational Data in Formulary that addresses best practices for substantially greater cost.5 Decision Making: Evaluation the design, implementation, and Criteria,” for internal use when evaluation of patient registries, Observational CER also offers the evaluating drugs for the purposes which is now in its second edition.10 ability to study particular issues such of improving health outcomes and Another initiative, which is actively as off-label use, patient adherence and providing value for its members.7 developing guidelines and checklists safety. As described by the Institute specifically for observational of Medicine in its July 2010 Letter Part of the challenge in using studies of CER, is the GRACE Report Ethical Issues in Studying the observational research for decision- (Good ReseArch for Comparative Safety of Approved Drugs, “some making has been the lack of clear Effectiveness) Principles.11 At the observational studies of safety have guidelines focused on enabling same time, many organizations are distinct advantages over trials….they researchers and decision makers to developing task forces, working can be larger, involve longer patient discern high quality research that groups, and best practice initiatives follow-up, include a broader diversity controls for bias and confounding for observational research include of patients and care settings, and be from work that is less reliable. High the Drug Information Association completed more quickly.” profile issues with treatments (such (DIA), the International Society as bone marrow transplantation of Pharmacoepidemiology (ISPE), Observational studies of CER are for breast cancer being adopted the International Society for also being used by government and based only on limited observational Pharmacoeconomics and Outcome private payers to make coverage case series8) are examples of why Research (ISPOR), and the European determinations. In the case of it is critical to raise the level of Medicines Agency (EMA), which the National Oncological PET understanding of what constitutes through its ENCePP network, Registry (NOPR), data from this ‘good’ observational research. recently released the Code of observational registry were used Whereas good practice guidelines Conduct for Independence and to examine the effect of positron have been well-established for Transparency and the Checklist COMPARATIVE EFFECTIVENESS emission tomography (PET) scans on experimental studies for some time, of Methodological Standards for physicians’ management of treatment until recently, best practices for ENCePP Study Protocols. as part of a Coverage under Evidence observational studies were extremely Development (CED) program. limited. With the growing focus on Just as CER names, definitions and Ultimately, results for NOPR have using observational research, several guidelines have been changing, changed the current Medicare groups have actively stepped up to the role that observational studies coverage requirements for several address the methodological concerns play in conducting CER is certainly tumor types and more are currently and to identify best practices that an evolving one. It is clear that under investigation.6 will result in high-quality evidence observational studies offer an development for decision making. approach to conducting real- Some private payers and pharmacy world research on populations and benefit managers, such as CVS The GRADE collaborative is an conditions not generally studied Caremark, are also taking a more international consensus movement in RCTs and that are important to proactive approach and conducting that focuses on the quality of the decision makers. As the methods their own comparative and cost study, not the type of study, as a for developing and recognizing high

VOL 3 ISSUE 5 GLOBAL FORUM 43

SS4-Gliklich.indd 43 9/20/11 5:29 PM quality observational research for characteristics. JAMA. 1998 Apr 9. See http://www. particular questions continue to 22-29;279(16):1278-81. gradeworkinggroup.org/. Last improve so will its use in CER. In 4. Weinstein JN, Lurie JD, accessed July 22, 2011. the end analysis, experimental and Tosteson TD, Zhao W, Blood 10. Gliklich RE, Dreyer NA, observational research methods are EA, Tosteson AN, Birkmeyer eds. Registries for Evaluating complementary and both are needed N, et al. Surgical Compared Patient Outcomes: A User’s to fully develop an evidence base for with Nonoperative Treatment Guide. 2nd ed. (Prepared most health care decisions. for Lumbar Degenerative by Outcome DEcIDE Center SpondylolisthesisJ Bone Joint Surg [Outcome Sciences, Inc. d/b/a References Am. 2009;91:1295-304 Outcome] under Contract No. 1. http://ww.cms.gov/medicare- 5. Lindenauer PK et al. Association HHSA29020050035I TO3.) AHRQ coverage-database/details/nca- of corticosteroid dose and route Publication No.10-EHC049. proposed-decision-memo.aspx? of administration with risk Rockville, MD: Agency for NCAId=220&ver=18&NcaName of treatment failure in acute Healthcare Research and Quality. =Screening+Computed+Tomogr exacerbation of COPD. JAMA September 2010. aphy+Colonography+(CTC)+for 2010;303:2359-2367. 11. See http://www.graceprinciples. +Colorectal+Cancer&MEDCAC 6. http://www.cancerpetregistry. org Last accessed July 22, 2011. ■ Id=45&fromdb=true&IsPopup=y org/news.htm#NOV202008. Last &bc=AAAAAAAAIAAA&. Last accessed July 22, 2011. accessed July 22, 2011. 7. Wellpoint use of comparative 2. Committee for Medicinal Products effectiveness research (CER) and for Human Use. The Rules observational data in formulary Governing Medicinal Products in decision making: evaluation the European Union – Guidelines criteria. May 2010. https:// on Pharmacovigilance for www.wellpointnextrx.com/ Medicinal Products for Human shared/noapplication/f1/s0/t0/ Use. 2008 Vol 9a. pw_b145032.pdf. Accessed July 8, 3. Wennberg DE, Lucas FL, 2011. Birmeyer JD, Bredenberg CE, 8. Richard A. Rettig, Peter D. Fisher ES. .Variation in carotid Jacobson, Cynthia M. Farquhar endarterectomy mortality in and Wade M. Aubry. False Hope: Richard Gliklich, MD, is the the Medicare population: trial Bone Marrow Transplantation for President and CEO, of Outcome. hospitals, volume, and patient Breast Cancer. Oxford Press 2007. COMPARATIVE EFFECTIVENESS COMPARATIVE

44 GLOBAL FORUM OCTOBER 2011

SS4-Gliklich.indd 44 9/20/11 5:29 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

Drug Industry, Regulators and Payers: CONVERGENCE OR DIVERGENCE?

Lloyd Sansom

s we face the future in using indirect comparisons. This measures are often a source of health care, all countries adds uncertainty to the evaluation disagreement between sponsors and A will be confronted by an and often becomes problematic decision makers. It is unreasonable increasing demand for health because of differences in the baseline to expect sponsors to be able to services due to changing characteristics of trial participants, design appropriate trials using demographics, escalating cost and outcome measures, duration of the generally accepted endpoints if limited investment in unmet areas of trials or the inclusion and exclusion there is no internationally accepted health need. The cost of criteria. framework for MCSDs. Similarly, the pharmaceuticals continues to issue of agreed quality of life (QoL) increase and many countries are Clinical trial designs that address measures for specific diseases needs facing the challenge of maintaining the requirements of the regulators to be undertaken. There should be equitable access to new agents. The and payers are essential. In the past, no reason why an internationally role of the payer has become clinical trials have been dictated by endorsed guidance manual for increasingly important, as the payer the requirement of the regulators, QoL measurements for specific is often the gatekeeper for sponsors leaving payers with attempting to diseases could not be produced and to the market and for patients to make decisions in the absence of maintained to assist industry in access. This contrasts with the past adequate data. This does not mean designing trials. where the regulator was often seen as that active comparator trials need the only hurdle to access. The to be undertaken on all occasions, The measurement of QoL endpoints disciplines of health technology since to do so would inevitably within a clinical trial is seldom assessment and health economics require larger, more expensive, and undertaken. This is surprising have developed over recent years, less timely trials. However, this raises since many of the therapeutic and most countries now have formal the question of whether there is interventions today are specifically processes to examine the cost consideration by sponsors of what designed to improve a patient’s effectiveness of new therapies. the likely acceptable comparator may QoL. A good illustration is the use However, the data requirements of be (accepting this can differ from of medicines in the management payers and regulators are often quite country to country), and whether the of intermittent claudication. The different and the pharmaceutical inclusion/exclusion criteria, endpoint measure used by regulators is the industry has been tardy at measurements, study duration, etc. improvement in the 6-minute walk recognizing the specific data needs of used in the trials of the comparator test (although no MCSD appears COMPARATIVE EFFECTIVENESS payers. should be considered in the design of to be set), but in none of the trials the new trial. While it is appreciated seen by this author has a QoL In order to evaluate cost that clinical sciences continually measurement been included in the effectiveness, the incremental develop, these potential confounding trial. This is surprising since the benefit of the new technology over issues need to be considered major reason for the intervention its comparator needs to be assessed. early in the drug development is to enable patients to perform Invariably the regulator uses placebo process. There also needs to be an functions of daily living without pain. as the comparator; whereas, the international agreement between From a payer perspective the absence payer will usually wish to compare regulators and payers with regard of QoL measures in the trials is a the new agent with an active to ‘minimum clinically significant missed opportunity and represents intervention that the new therapy differences (MCSD)’ for accepted the lack of awareness of sponsors to will replace in clinical practice. endpoints used in health technology optimize the outcomes from trials Clinical trials using an active assessment. For example, there by thinking prospectively about comparator are not common and appears to be agreement in reduction what purpose the data will serve. In payers are left with the dilemma of of systolic blood pressure or intra- fact, one could also argue whether undertaking cross-study evaluation ocular pressure, but many other it is ethical to undertake such trials 45

SS5-Sanson.indd 45 9/20/11 5:29 PM without QoL measurements, a banner of “progressive licensing” regard to content and transparency. topic which should be put to ethics by regulators or “coverage with There is an urgent need for an committees for response. evidence development” by payers. international standard for registries This acknowledges the need to for selected diseases that can be The need for methodological extend knowledge (with associated maintained by an independent development to assist regulators uncertainty) from efficacy measures organization, and for the data to be and payers in decision making is in clinical trials to effectiveness accessible to approved agencies/ becoming critical. One example in clinical use. In the past, such researchers. is the requirement by ethics monitoring has been associated with committees, particularly in cancer signal detection for toxicity, but The paradigm is shifting from trials, to allow early crossover from increasingly it will be used by both parallel independence to integrated the reference arm - commonly regulators and payers to compare dependence on behalf of industry, placebo - to the active arm if the effectiveness and pharmacoeconomic regulators and payers. Such a shift interim analysis of the data signals an benefit. Currently, the primary is essential if the issues facing advantage in disease progression. The reasons for post-market data us all are to be addressed in the analysis of the data is problematic, collection are to address the coming years. We must be smarter and there is no internationally uncertainties that inherently exist in the way we operate; we must accepted guidance. Such data is in clinical trial outcomes, and to acknowledge that while we each have likely to be highly confounded and allow access to medicines that may our own requirements and need for the use of such methods as “Rank address a high unmet clinical need independence and responsibility, Preserving Structural Failure Time in a timely fashion. However, the there is a large amount to be gained Method” and “Inverse Probability way in which post-market data is by a more open and proactive Weighting Method” are being collected and analysed is still fraught dialogue. This is crucial to ensure used by sponsors. However, there with ambiguity. Observational data that challenges that face us all are is no general agreement as to the is likely to be highly confounded better addressed for the sake of the limitations of these methods and and may simply add “uncertainty patients. “We cannot change the under what circumstances their to uncertainty”. New techniques to direction of the wind, but we can use may or may not be appropriate. address these issues are urgently adjust our sails to go in the direction Since over one-third of all current needed. We must develop methods we want.” ■ drug trials are related to oncology, that can be used on an international and many will have a requirement basis using a variety of data sources. for early crossover, the need for an International comparisons will international consensus is critical. be essential if we are to identify Another issue that requires some those pharmacogenomic and agreement is how to analyze cross- pharmacokinetic determinants of study comparisons, particularly patient outcomes. Further, the use using dichotomous outcomes. When of registries, particularly for orphan the result of such an analysis can be or ultra-orphan diseases, needs dependent upon whether relative risk to be improved. The extremely or odds-ratios are used, clearly some high cost of orphan drugs and the deficit exists in our ability to apply limitations of quality in many orphan methods appropriately. disease clinical trials will require the Emeritus Professor Lloyd Sansom, creation of such data sets. However, AO is with the Division of Health Increasingly, the issue of post- at the present time, registries are Sciences, University of South

COMPARATIVE EFFECTIVENESS COMPARATIVE marketing data collection is commonly maintained by the Australia located in Adelaide, being discussed either under the industry and lack consistency in Australia. 46 GLOBAL FORUM OCTOBER 2011

SS5-Sanson.indd 46 9/20/11 5:29 PM DIA LEASES OFFICE IN WASHINGTON, DC

o facilitate access to government agencies, T regulatory agencies, and other organizations and potential partners with shared interests (such as the institute of medicine and the national institutes of health), DIA has leased a single office in Washington, DC. Our leasing agreement also entitles us to reserve several small and medium-sized conference rooms at the location on a first come, first served basis.

DIA’s Washington DC office is located at 888 16th Street, NW, Suite 800, Washington, DC 20006 Telephone: 202.349.0872; Fax: 202.349.0874

1

AN5-Washington DC.indd 1 9/20/11 5:46 PM UE1-UpcomingEvents.indd 48 48

UPCOMING EVENTS

UPCOMING EVENTS GLOBAL FORUM October 28,2011 October Conferences In theAmericas NOVEMBER 78,2011 NOVEMBER 34,2011 NOVEMBER 2,2011 NOVEMBER 12,2011 NOVEMBER 2526,2011 OCTOBER 1314,2011 OCTOBER 1113,2011 OCTOBER 1112,2011 OCTOBER Philadelphia, PAPhiladelphia, Approval: 2andBeyond Phase Vaccine and Development Washington, DC Worldin Real Settings Health Technology Assessments to Comparative Effectiveness the Marketplace: Applying EvidenceMaking Matter in VALansdowne, WorkshopDesignation Drug Orphan DIA/FDA Canada Ottawa, Partnerships New Frameworks New Models- 2011: New Annual Meeting Canadian DIA MD Bethesda, Right Patients the for Selecting Methodologies and Issues Practical TailoredDIA/FDA Therapies: MD Bethesda, Labeling Harmonize for to Companies Strategies Labeling Safety Harmonized AreHow We Close to –2011: Harmonization Labeling Washington, DC Products and Orphan US Conference Diseases onRare MD Bethesda, The Future What’s ofSPL: Next? Washington, DC Workshop of Human Pharmacokinetics Models Predictive DIA/PhRMA OCTOBER 2011,VOL 3ISSUE 5 October 13-14,2011 October Training Courses In theAmericas OCTOBER 2628,2011 OCTOBER 2627,2011 OCTOBER 2427,2011 OCTOBER 2425,2011 OCTOBER O O OC O OCTOBER 1012,2011 OCTOBER NOVEMBER 1617,2011 NOVEMBER C C C Horsham, PA andAuditingPractices Clinical toIntroduction Good Horsham, PA Pharmacovigilance & Postmarketing Safety Drug Francisco,San CA Experience Leadership Horsham, PA Pharmacovigilance & Safety Premarketing Clinical Horsham, PA Statisticians for Statistics Non- Clinical Horsham, PA Meeting Committee for aUSFDAPreparing Advisory Horsham, PA NDA Phase II:The Part Affairs Regulatory Horsham, PA Management Risk Project Horsham, PA Management and Lifecycle Development Product Drug New Horsham, PA Project Clinical San Diego, CA Diego, San SubmissionStandards Electronic into the Next of Generation Conference: Moving Anniversary Submissions2011:10th Electronic T T T T OBER 2425,2011 OBER OBER 20,2011 OBER OBER 1719,2011 OBER 1314,2011 OBER

Management EudraVigilance Europe NOVEMBER 710,2011 NOVEMBER 78,2011 NOVEMBER OCTOBER 1214,2011 OCTOBER NOVEMBER 2123,2011 NOVEMBER 1718,2011 NOVEMBER 15,2011 NOVEMBER 1416,2011 NOVEMBER 2728,2011 OCTOBER 2426,2011 OCTOBER Philadelphia, PAPhiladelphia, II:TheNDA andPart Phase Phase 1:TheIND Part Affairs Regulatory PAPhiladelphia, Course Learning Blended Monitoring Fundamentals Research ofClinical London, UK London, the EEA in ofICSRs Reporting Electronic EudraVigilance training- UK London, training course (EVMPD) Dictionary Product EudraVigilance Medicinal UK London, (11th) EudraVigilance Information Day UK London, the EEA in ofICSRs Reporting Electronic EudraVigilance training- UK London, training course (EVMPD) Dictionary Product 2011EudraVigilance Medicinal UK London, the EEA in ofICSRs Reporting Electronic EudraVigilance training- UK London, the EEA in ofICSRs Reporting Electronic EudraVigilance training: 9/20/11 4:32 PM 49 UPCOMING EVENTS 9/20/11 4:32 PM

GLOBAL FORUM GLOBAL Training Course on Introduction to Training Signal Detection and Data Mining in Pharmacovigilance Berlin, Germany Assessment DIA Technology Health Course Training (HTA) Basel, Switzerland US Regulatory Affairs: A ReviewComprehensive of Regulatory Procedures INDs and for US in the NDAs Paris, France Course on Good Training of MedicalManagement Devices Diagnostics and including In Vitro Diagnostics:Companion Legal and Practical Aspects as used in Personalised Medicine Zurich, Switzerland The New Individual Case Safety Report (ICSR) International Standard and ICH E2B/M2 (3rd) Day Information London, UK on Non-Clinical course Training Safety Sciences Their and Regulatory Aspects Lisbon, Portugal Course on Clinical Project Training - PartManagement I Austria Vienna, eCTD Course for - Training Submissions in Switzerland Zurich, Switzerland NOVEMBER 89, 2011 NOVEMBER 1011, 2011 NOVEMBER 1416, 2011 NOVEMBER 1417, 2011 NOVEMBER 16, 2011 NOVEMBER 2125, 2011 NOVEMBER 2123, 2011 DECEMBER 8, 2011 5 3 ISSUE VOL Facilitating Regulatory Facilitating Approvals - Opportunities for in Turkey Regional A Harmonisation? Organised DIA by the Workshop Advisory Council of Europe Istanbul, Turkey 2011 on European Conference 12th Electronic Document EDM Management/ Zurich, Switzerland Joint DIA/MHRA Workshop on DIA/MHRAJoint Workshop MedicinalAdvanced Therapy Products London, UK Training Course on How to to Course on How Training Pharmacovigilance for Prepare and InspectionsAudits Berlin, Germany Training Course on European Training Regulatory Affairs: In-depth Review Registration of Current Procedures European in the Union Paris, France Training Course on Quality Training by Design: New Concepts for Development & Manufacturing - A Hands-on Course Pharma for Austria Vienna, Training Course on Essentials of Training Clinical Management Study Paris, France Training Course on Practical GCP Training and of Trials Auditing Compliance Systems London, UK DECEMBER 5, 2011 NOVEMBER DECEMBER 30 2, NOVEMBER 18, 2011 NOVEMBER 78, 2011 NOVEMBER 34, 2011 NOVEMBER 34, 2011 NOVEMBER 34, 2011 OCTOBER 2628, 2011 Training Europe 5th Annual Clinical Forum 2011 Clinical Forum Annual 5th Basel, Switzerland Strategies for Testing DART Pharmaceuticals:Human Animal Approaches Models vs In-Vitro Leiden, Netherlands DIA/EMA2nd Joint Statistics Workshop London, UK Cardiovascular European 5th 2011: Safety Conference Benchmark the Advancing CV for Safety in Diabetes, Obesity and Oncology Clinical Development Barcelona, Spain DIA/EMA2nd Joint ENCePP Day Information London, UK DIA/EMA/FDAJoint Orphan Drug Designation Workshop London, UK Quality Risk in Management Clinical Drug Development Conference Berlin, Germany Introduction to Introduction to Pharmacovigilance and Electronic of Individual Case Transmission Safety Reports use the (ICSR) for of Eudravigilance London, UK training- EudraVigilance Electronic Reporting of ICSRs in EEAthe London, UK OCTOBER 1012, 2011 OCTOBER 1011, 2011 OCTOBER 2628, 2011 NOVEMBER 34, 2011 NOVEMBER 7, 2011 NOVEMBER 1011, 2011 DECEMBER 6, 2011 DECEMBER 79, 2011 Europe Conference NOVEMBER 1011, 2011 UE1-UpcomingEvents.indd 49 UE1-UpcomingEvents.indd 50 50

UPCOMING EVENTS

UPCOMING EVENTS

Conference Japan Conference India Conference China OCTOBER 2526,2011 OCTOBER NOVEMBER 26,2011 NOVEMBER 2728,2011 OCTOBER 1617,2011 DECEMBER 1518,2011 OCTOBER 2324,2011 OCTOBER GLOBAL FORUM Shanghai, China Submission From Patient to Data GCP: with Study inthe Data Compliance ofClinical andIntegrity Quality Tokyo, Japan Development Trend- New for Clinical Global Japan Annual8th DIA Meeting Mumbai, India Patients Access to Benefit Strategies andMarket Medicine, Science, Convergence of Development: andClinical Discovery Drug 6th Annual Conference on Shanghai, China Validity ofTrial Results TrialsClinical to Ensure the False PositiveOverall Rate in Control Development: for Drug Research inClinical Thinking Understanding the Statistical Tokyo, Japan Japan Workshop Labeling 1st DIA in Mumbai, India ComplianceCMC Forum: Quality Pharmaceutical OCTOBER 2011 Program Program InvestigatorClinical eLearning Program Communications eLearning Medical e-Learning Training EudraVigilance Other Latin America NOVEMBER 2729,2011 NOVEMBER 20,2011 NOVEMBER 1921,2011 OCTOBER NOVEMBER 1011,2011 NOVEMBER 79,2011 NOVEMBER Module 1 and Quality Module 3 Module 1andQuality Module Focus onEU Requirements: AbuDhabi, United Arab Emirates Training Dossier onCTD Course training course (EVMPD) Dictionary Product Argentina Aires, Buenos Research Role inWorldwide Clinical America Latin Research Clinical of Congress American 8th Latin Foreign Act Practices Corrupt Professionals Interactions Healthcare with Eucomed Guidelineson Code ofthe AdvaMed Basics Code ofthe PhRMA Basics Program Compliance eLearning Validation 11 andPart Program eLearning GMP Pharmaceutical Program eLearning Pharmaceutical Clinical Kaplan EduNeering Consen Informed Marino San Marino, San Dictionary Product EudraVigilance Medicinal Marino San Marino, San the EEA in ofICSRs reporting Electronic EudraVigilance training- Introduction toIntroduction USInstitutions toIntroduction the International toIntroduction the European toIntroduction Japanese Medicinal How to Register Medicinal How to Register Medicinal How to Register in Drug aNew How to Register How to Maintain Marketing Access to Unapproved Drugs modules elearning IDRAC following the to provide Reuters Thomas with partnered has DIA NEW! byIntellego Zenosis and Regulatory Authority (FDA)and Regulatory (ICH) Conference onHarmonization Authority Regulatory Union Institutions and Authorities Institutions andRegulatory Procedure Recognition through the MutualProducts Procedure Decentralized through the Products Procedure through the Centralized Products the USA Centrally Products Authorized Approvals inEurope for ofPharmacovigilance Basics Trials ofClinical Basics through Compassionate Use Registration Drug (PD/PD)in Pharmacodynamics and Pharmacokinetics inthe US Products Generic FDAObtaining Approval for The ANDA: for Requirements Antibodies ofMonoclonal Registration Authorizations inEurope Variations to Marketing Anti-bribery Global Compliance Device to Medical Introduction 9/20/11 4:32 PM 51 UPCOMING EVENTS 9/20/11 4:32 PM

GLOBAL FORUM GLOBAL VOL 3 ISSUE 5 3 ISSUE VOL 12:00 – 1:30pm Regulatory Aspects of Clinical Series Studies Online Training OverviewWebinar: of FDA Industry for Guidance on Submission of Summary Bioequivalence ANDAs Data for 10:00 – 11:30am in Emerging Win to Invest Value of Integrated Markets: The Regulatory and Commercial Online Training Intelligence Series Master File Trial Webinar: Series Part 4: Webinar and Maintenance Management Content of eTMF 11:30am – 1:30pm a Clinical Art of Writing Overview Series Online Training Master File Trial Webinar: Series Part 3: Moving Webinar from a Paper an Electronic to of Process Management for Content TMF 12:00 – 2:00pm Development of a Clinical Study Series Report Online Training 12:00 - 1:30pm Project Information, and KnowledgeCommunication Online Training Management Series NOVEMBER 30, 2011DECEMBER 2, 2011 OCTOBER 18, 2011 NOVEMBER 16, 2011 OCTOBER 11, 2011 NOVEMBER 14 NOVEMBER 18, 2011 OCTOBER 4, 2011 NOVEMBER 7 NOVEMBER 11, 2011 NOVEMBER 1NOVEMBER 22, 2011 Webinars 10:00 – 11:30am The Regulatory Landscape and ProductKey for Considerations Development in Emerging Series Regions Online Training 12:00-1:30pm of Project Fundamentals Non-Project the for Management Series Manager Online Training 12:00 – 1:30pm Reporting Event Adverse Requirements: IND and Online Training Post-marketing Series 12:00 – 1:00pm Supplements and Other Changes Application an Approved to Series Online Training 12:00 – 1:30pm Monitor? Monitoring the Who’s Series Online Training 11:00am – 12:30pm in Clinical Research Key Topics Series Online Training Regulatory Agencies and Japan Union European eCTD in Conduct of Clinical Trials Europe Submission of Investigational New in the Drug Applications USA (INDs) of a Drug Cycle OCTOBER 26NOVEMBER 2, 2011 OCTOBER 27NOVEMBER 4, 2011 OCTOBER 35, 2011 OCTOBER 6, 2011 OCTOBER 1428, 2011 OCTOBER 2426, 2011 Online Training Series Online Training Online Training Series Online Training Meeting Opportunities with Orphan Drugs USA, in the Overview CTD of the and the Regulatory Requirements the for Regulatory Requirements the for The Regulatory Development UE1-UpcomingEvents.indd 51 GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

DIA & FDA Team for Tailored Therapeutics Conference

Chris Slawecki

n October 25-26, DIA and the scientific, clinical, and regulatory Binkowitz (Senior Director, Clinical FDA will present our fields: Dr. Janet Woodcock, Biostatistics, Merck & Co., Inc.) O co-sponsored conference Director, CDER, FDA; Dr. Frank R. and Dr. Sue-Jane Wang (Associate DIA/FDA Tailored Therapeutics: Lichtenberg, Courtney C. Brown Director for Adaptive Design & Practical Issues & Methodologies for Professor of Business, Columbia Pharmacogenomics, Biostatistics Selecting the Right Patients at the University; and Dr. Stephen J. Ruberg, Leader for Biomarker Qualification, Bethesda North Marriott Hotel & Distinguished Research Fellow Office of Biostatistics, Office of Executive Conference Center in and Scientific Leader, Advanced Translational Sciences, CDER, Bethesda, MD. This multidisciplinary Analytics, Global Statistical Sciences, FDA). Drs. Binkowitz and Wang conference will address the potential Eli Lilly and Company. Dr. Ruberg will open this conference with impact of tailored therapeutics on will also chair the session “Subgroup welcoming remarks and close the biomarkers, diagnostic tests, clinical Identification When Biomarkers conference with the final “Next trial operations and regulatory Are Unknown – Exploratory Step” session; in between, Dr. Wang implications, personalized medicine, Approaches,” and shared his thoughts will chair the session on “Subgroup and other aspects of drug on his keynote, which will address Identification When Biomarkers Are development. It will also encompass “Drug Development Challenges for Well Known: Assessment of Clinical multiple therapeutic areas, including Therapeutics,” and on this conference Utility of Biomarkers” and the panel oncology, cardio-renal, HIV, below. An abstract of Dr. Woodcock’s discussion on the future of tailored pediatrics, psychiatrics, and more. planned remarks is also provided therapeutics, while Dr. Binkowitz below (see accompanying box). will chair the panel discussion on The first day of this two-day subgroup identification. Prior to conference will be highlighted by DIA/FDA Tailored Therapeutics the conference, they shared these keynote addresses from leaders in will be co-chaired by Dr. Bruce thoughts with the Global Forum. NORTH AMERICA NORTH

52

GR7-TailoredTheraputic.indd 52 9/19/11 12:01 PM 53 NORTH AMERICA 9/19/11 12:01 PM

GLOBAL FORUM GLOBAL in the near of diagnosticsin the Use future. is one example tailor therapy to of enrichment. The guidance will scientific adviceon extensive have carryingout these sorts of programs. approved many the In addition to drugs tailored are toward that efficacy parameters, progress has been safety area. made in the The Serious Event International Adverse Consortium (iSAEC) and other identifiedgroups genotypes, have particularly HLA alleles, that increasedconfer risk of various serious side effects, particularly drug induced liver injury and skin hypersensitivity reactions as such Stevens is Johnson syndrome. It progressexpected in major that scientificunderstanding basis the for “idiosyncratic” drug reactions will five years.occur next in the CDER is pursuing research molecular on the mechanisms underlying these discoveries. obstacleThe major progressto in area of tailoredthe therapeutics has been and development identification diagnostic.of an appropriate This has be to difficult. proven quite As areas in many of new technology, it is expected improvement that will rapidly be first and then slow at as is enough experience accelerate time! that all await gained. We In sum, tailored therapeutics will be part a major future of of the medicine. They dependability the on diagnostic; developto a a reliable is ongoing.challenge that As this is solved,problem we can look forward effective a future of more to can be that therapies and safer develop faster case is the than with drug development today. 5 3 ISSUE VOL consulted on 18 BLAs,consulted 54 NDAs, and had genetic data.138 INDs that The heart of is tailoredtherapies a diagnostic: perhaps an in vitro test, diagnostic imaging, or other test (e.g., EEGs, ECGs, pulmonary function tests and so FDA forth). has out made progressin laying so-called for a path companion diagnostics (in vitro tests used to select or direct In drug therapy). released FDA a draft year, of this July subject.guidance on this CDER and CDRH worked out procedures have review allow concomitant to of drugs and diagnostics during both stage and the investigational the process.pre-market In addition, CDER has re-established a Division dedicated imaging to agents in order anticipated the accommodate to flood of new imaging technologies. CDER released a draftRecently, of drugguidance on “Qualification This guidance development tools”. out an innovative newlays process evidence which the through to support new and other biomarkers tools in drug development can be guidance”. under FDA generated hasThere been an enthusiastic response new this to process from consortia wishing qualify to a wide variety of diagnostics. released FDA a Additionally, draft guidance on “Developing of investigational combinations drugs” in Dec 2010. This guidance is particularly pertinent tailored to therapeutics, require which may to targeting of several pathways achieve a lasting effect. CDER release plans to a Finally, guidance Designs” on “Enrichment Keynote Abstract: Dr. Janet Woodcock Woodcock Janet Abstract: Dr. Keynote The Rise of Tailored Therapeutics The Rise of Tailored This August,approved two This FDA within weekscancer therapies of Xalkori (cirizotinib) and each other. Zelboraf (PLX4032) approved were subsets treat to of individuals with cancer and lung non-small-cell metastatic respectively. melanoma were patients appropriate The diagnosticsidentified by companion assessedthat certain properties of tumors.the These therapies two developedwere very and approved most to cancer compared rapidly drug development, and illustrate of a tailored promise some of the cancer interventions.to approach Because safer, for potential of the effective,more rapidly and more developed drugs, has been FDA advocating tailored for therapeutics over a decade.for Such therapeutics individualizedare identify to withpatients a higher probability of of response, exposure avoid or to withpatients a higher probability adjust dosing and to to of toxicity, in metabolism.reflect differences Because of initial industry reluctance with the such information share to put forth the in 2002 FDA Agency, idea harbor of a safe scientific for discussion, which evolved the into Genomic Data Submission Voluntary Process, Voluntary the into and then Exploratory Data In Submission. 2004, these ideas crystallized were as part Critical Initiative, of the Path in which tailoring therapeutics was promoted as a tool improving for drug development. CDER has approach this promote to continued workshops dialog. and other through discussion of the hasMuch moved voluntaryfrom the submission everyday the phase into regulatory process. our genomics In 2010, group GR7-TailoredTheraputic.indd 53 Why did you agree to serve particular therapeutic area. This is requires an efficient translational as co-chair for this because we would like all attendees infrastructure. Regulatory importance conference, and what are some of to take home a deeper understanding on the path to personalized medicine the new clinical and/or regulatory of the topic of tailored therapeutics, has been noted by Drs. Margaret ideas that you hope attendees take as well as a broader perspective of all Hamburg (FDA Commissioner) and home from this conference? the different disciplines it will take Janet Woodcock (CDER Director, to effectively implement tailored FDA) in recent years. As a regulatory Bruce Binkowitz: I believe that therapeutics. I more than hope – I health agency, regulatory and scientific statisticians have unique training am confident that our collective scrutiny for proper statistical inference and therefore can bring unique effort will allow attendees to take is critical. Naturally, the degree of qualities to leadership positions. home an understanding of all these statistical and scientific rigor differs Statisticians are trained in scientific issues, the incredible potential between exploration and evidence methodology and are constantly public health value of successfully setting. searching for bias, confounding, implementing tailored therapeutics, and errors – most commonly, false and the desire to learn more about I’m honored to work in this positive and false negative errors. and ultimately implement what we capacity with our respected Co- Statisticians can integrate data discuss over our two day workshop. chair and organizing committee to and opinions in a way that yields collaboratively design this tailored understandings of the probabilities, Sue-Jane Wang: Prior to joining therapeutics workshop so it is suitable as well as the uncertainties, of what FDA, I worked at the Medical for interested professionals. We is observed. Statisticians must be Genetics Institute of Cedars-Sinai anticipate that both the overwhelming good communicators, to extract Medical Center, tackling interesting interests from the drug/diagnostic the correct information from those and challenging statistical issues industry, and the evidential needs who seek statistical expertise and related to medical genetics, in regulatory evaluation, will be to then translate "statistics" back to epidemiology, molecular biology, collegially discussed, and we hope to plain language. To provide the most and cytogenetics of common get closer to actualizing our important value, a statistician must possess diseases and genetic diseases, led public health mission through this good working knowledge of the by Co-director Dr. Jerome Rotter, workshop. subject matter at hand, and the who made a historical statement ability to understand the specific for that time, that, “Genetics will be business needs of the inquirer. I mainstream in the 21st century.” I agreed to co-chair this conference have been passionate about genetics because this is a critical topic that and its potential impacts on human lies straight ahead in the future of diseases and therapeutic effects ever medical product development. I also since. This passion has furthered my believe that I have a responsibility, professional involvement: I joined as a statistician, to lead efforts that FDA when the Human Genome bring important topics to a wider Project had just completed and the audience. For statisticians to truly exciting fields of pharmacogenetics lead in any endeavor, we must and pharmacogenomics were gradually understand the area in which we are emerging, although their terminologies providing consultation: The medical were not yet harmonized. BruceBruce BinkBinkowitzowitz area, the regulatory environment, what the literature and experts are I agreed to serve as Co-chair for this saying, and how to integrate all these conference due to this passion and aspects into our current business and my roles as Associate Director for political environments. Pharmacogenomics, Biostatistics Leader for Biomarker Qualification I was very fortunate to work in the Office of Biostatistics, Office with an extremely enthusiastic, of Translational Sciences, CDER, knowledgeable, and effective co- and as a Statistical Delegate working chair and committee. Our program with regulatory scientists through committee has purposely created a our Inter-Center collaboration. These program of broad scope. We did not responsibilities have helped me witness target any particular professional the important roles statisticians can expertise or discipline, any particular play both in the search of biomarkers Sue-JaneS J WangW

NORTH AMERICA NORTH phase of development, or any and in the evidence-setting that

54 GLOBAL FORUM OCTOBER 2011

GR7-TailoredTheraputic.indd 54 9/19/11 12:01 PM 55 NORTH AMERICA 9/19/11 12:01 PM

GLOBAL FORUM GLOBAL marker interactions.marker approach This with statistical issues and is fraught does not lead easily to interpretable results. on Subgroup identification, hand, uses modern other more the mining techniquesdata along with statisticalsuitable methods for identify adjustments to multiplicity subgroup who may of patients the respondersbe – be exceptional it efficacyexceptional response or risk of adverse events.exceptional I personally believe we should that Phase examine II and routinely Phase III trials subgroups for of responders regardless exceptional patient overall of whether the shows study population in the a significant effect or not. For statistical test of the the example, effect medicine’s investigational group may a control to compared achieve statistical significance, but effect bethe may driven primarily has an subgroup that by a large response blendedexceptional with shows a smaller subgroup that is importantno response. for It in healthall stakeholders care (pharmaceutical companies, regulators, physicians, and payers and understand this to patients) the label to with regulators work medicationapproved accordingly. overall statistical the Conversely, test of a medicine versus control not achievemay statistical significance, overall outcome but the subgroupis driven of non- by a large responders and a smaller subgroup do responders.of exceptional We 5 3 ISSUE VOL Because this topic is of interest to researchers allows a company to make labeling make labeling to allows a company claims in agreement with regulatory actively authorities and, thereby physicians to treatment the promote say to ability and patients. is the It with a high level that of certainty medicine works“this better in a subgroup defined patient by this medication and the does not marker, subgroup all in the as or at work well the of patients who do not have marker.” Examples tailored of therapeutics Erbitux® colorectalare for cancer in wildpatients with the type KRAS non-small for gene, and Alimta® with lung cancer nonsquamous cell histology. across disciplines, many DIA the Therapeutics Conference Tailored is targeted a diverse at audience. Speaking from your statistical background, future on what contributions in tailored therapeutic research would you like to see your fellow statisticians focus? emphasizeI want to difference the between has what been historically analysis” and called“subgroup Eli Lilly and at I and others what characterizeCompany as “subgroup past In the and even identification.” subgroup by analysis is done today, severalexamining possible dozen covariates) on a one-at- (or markers a-time basis assess to treatment-by- Q&A with Keynote Speaker Dr. Stephen J. Ruberg Speaker Dr. Q&A with Keynote One of the purposes of this conference is to “increase awareness” and “clarify awareness” and “clarify terminology” regarding tailored therapeutics. Broadly speaking, aspectswhat of tailored therapeutics do you hope this conference will increase awareness of and what terminology do you hope it will help to clarify? we all want that fair say to it’s I think suited more for medicines are that our specific needs to or ‘tailored’ our specific genetic make-up. With advances in science – including our understanding of disease processes of genetics role and the – opportunitiesthe customizing for individuals to hastreatments never been greater. A tailored therapeutic is a treatment is substantial which there for works evidence treatment the that better in a marker-identified group +) than of patients (marker its complementary subgroup -). The marker can (marker be any measurable characteristic patient of characteristics.or combination By substantial evidence, I mean clinical trials well-controlled having a statistically demonstrate that significantly better response an to compared treatment investigational group) control other (or placebo to the patients than (marker+) in the statistical patients. is the It (marker-) efficacyproof of differential in that one subgroup versus another GR7-TailoredTheraputic.indd 55 not want to ‘kill’ medicines that Keynote Address for our readers armamentarium of analytical skills have substantial benefits to patients, who are planning to attend this and tools to find the right medicine even if it is a smaller subgroup of the conference? for the right patient. overall disease population. I will be describing some of the I am passionate about searching for I would also like the statistical terminology and issues described medicines that can extend or improve community to engage in more above – tailoring to subgroups of patients’ lives, and I am doubly discussion about the appropriate patients, subgroup identification passionate about playing a leadership use of subgroup identification and subgroup analysis. I will also role in revolutionizing the practice of tools, multiplicity adjustments and review some ideas around the degree medicine through the application of the degree of evidence required to of evidence required to secure sound statistical design and analysis label a medication for a particular regulatory approval to make a labeling approaches. I must say that I am subgroup of patients. These are very claim for a tailored therapeutic. I privileged to come to work every complex issues, and they deserve have some ideas and proposals which, day in pursuit of finding the best our very best thinking in order to importantly, maintain scientific medicines for patients, and equally deliver on the promise of finding rigor and adhere to good statistical privileged to work for a company the right medication for the right principles, but do not add to the long completely committed to finding patient. and expensive clinical development the right patients so we can improve process. Finally, I will challenge my individual patient outcomes. As a May we ask you to preview statistical colleagues to be “scientific colleague of mine says, “How cool the major points of your detectives,” and to use their full is that!” ■ NORTH AMERICA NORTH

56 GLOBAL FORUM OCTOBER 2011

GR7-TailoredTheraputic.indd 56 9/19/11 12:01 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

DIA’S “NEW” 9TH ANNUAL CANADIAN MEETING

hile new scientific, Mr. Blake was inducted into the Neerja Goyal: The title for this industry, and regulatory Canadian Pharmaceutical Marketing year’s meeting is a reflection of W developments continue Hall of Fame; in 2008, he was named the evolving environment we’re to impact the strategies and Communicator of the Year by the in. There is a tremendous amount operations underlying clinical International Association of Business of change impacting the pharma discovery and pharmaceutical Communicators. industry and requiring us to adapt development, DIA returns to Ottawa, or react to it. It’s impacting the way Ontario, to present our 9th Annual David Griller, PhD, FCIC, FRSC, we develop drugs: Gone are the days Canadian Meeting: New Models – (Partner, SECOR Consulting), a of the big “blockbusters.” Now we’re New Frameworks – New fellow of both the Royal Society of developing more targeted therapies Partnerships, October 31 through Canada and the Canadian Institute and personalized medicines. “New November 2 at the Marriott Ottawa of Chemistry, will deliver the second Models” refers to changes in how the Hotel. Keynote. The third Keynote will pharma industry is developing drugs be delivered by Paul Glover, who and the nature of the drugs being Developed to highlight changes was appointed Assistant Deputy developed. in drug development models, Minister of the Health Products regulatory oversight frameworks, and and Food Branch at Health Canada Alongside of this, regulators having emerging new opportunities among this past February. The meeting will to re-think how products should be traditional, and not so traditional, proceed thereafter along parallel regulated given the increasing impact health care partnerships, DIA will tracks through which attendees can of globalization. The regulatory present our 9th Canadian Annual explore the new models, frameworks, frameworks need to be flexible to Meeting in collaboration with the and partnerships intimated by the manage the unexpected, like the Canadian Association of Professional meeting’s title. H1N1 flu pandemic last year, as well Regulatory Affairs (CAPRA/ACPR), as the rapid change in science and the Clinical Research Association DIA’s 9th Canadian Annual Meeting technology. Everything is changing, of Canada (CRAC), and Canada’s will be co-chaired by Neerja Goyal and regulators need to be, and are, Research-Based Pharmaceutical (Director, Regulatory Strategy & thinking about how they effectively Companies (Rx&D). Policy, GlaxoSmithKline, Canada) regulate in such a challenging and Alice Hui (Manager, Regulatory environment. That is the meaning Two optional, pre-conference Project Management Division, behind the “New Frameworks” tutorials will provide primers Therapeutic Products Directorate, portion of the title. on project management in the Office of Business Transformation, biopharmaceutical sector, and on Health Canada). They shared As for “New Partnerships,” we’ve pre- and post-market benefit/risk the following thoughts on DIA’s seen and will continue to see new assessments. The formal meeting annual offering for our scientific, players in healthcare collaborate in will begin, after welcoming and industry, regulatory, and academic ways they haven’t before, as we all NORTH AMERICA opening remarks, with three Keynote stakeholders in Canada, with the try to work together to collectively Addresses that represent different Global Forum. improve healthcare delivery. but interconnected perspectives. The first Keynote will be delivered by May we ask you to explain You will also serve as chair Phillip Blake, who serves as President the background and purpose for the "Personalized and CEO of Bayer, Inc., Canada, and of this meeting's subtitle: "New Medicine: A Revolution in who will serve as Chair for Rx&D Models - New Frameworks - New Healthcare" and "Use of Scientific effective November, 2011. In 2006, Partnerships"? Data for Decisions about Patient

57

GR8-Canada Annual Mtg.indd 57 9/19/11 12:15 PM Care" sessions within this rewarding experience, so I was outcomes as efficiently, effectively, meeting's "New Models" track. happy to continue to contribute this and sustainably as possible. This May we ask you to summarize or year. I wanted to see the process session will explore a couple of preview these sessions for our through from the beginning. For interesting multi-stakeholder readers? me, participating with DIA has collaborations. The first one is been an opportunity to learn and GERA, the Group on Electronic NG: We tried to bring in different to engage both regulatory and Regulatory Affairs, an industry perspectives, so we’ve got three industry counterparts in discussion and Health Products Food Branch speakers from varied backgrounds on topics that I don’t always have an initiative, which we’ll explore who will each describe how opportunity to explore in such depth from both the industry and Health personalized medicine is impacting or from so many different facets, and Canada perspective. We’ll also them. We’ve got an industry speaker to meet individuals with whom I may explore the Canadian HIV Vaccines who will talk about how development not have had an opportunity to come Initiative, a collaboration between of personalized medicines is different into contact in my day-to-day work. the government of Canada and the from traditional drug development. Bill & Melinda Gates Foundation We’ve got a clinician’s perspective You will also serve as chair for and Canada’s contribution to the on how these advances in sciences the “Electronic Media: global HIV vaccines enterprise. are being translated into clinical Opportunities & Challenges of the delivery of medicine. We also have Electronic Dialogue” and What else would like to an interesting perspective from a “Collaborative Approaches” sessions share about this upcoming speaker representing the Centre of within this meeting’s “New Canadian Annual Meeting? Excellence in Personalized Medicine Partnerships” track. May we ask you (Cepmed), who will talk about the to summarize or preview these NG: One of the things we were value that personalized medicines sessions? quite deliberate about as a program can bring to health care in Canada. committee in setting up this year’s AH: The “Electronic Media” session conference is trying to give it The other session I’m chairing is seeks to explore the opportunities more of an industry focus based about the use of scientific data for and challenges of the electronic on feedback that we received from decisions on patient care. In today’s dialogue. What makes this topic so previous offerings. Hopefully that world, there’s so much information. interesting for me is how these media will come through in what people So much of what we hear is related permit an opportunity for dialogue experience at this year’s conference. to scientific research, and there’s and not just a one-way interface. We’ve also purposely changed things a lot of evidence being generated This is a timely and new topic for our up a little bit: We’re not following on pharmaceutical products in Canadian annual program, which the traditional tracks, where you’ve particular. This session will highlight had not explored social media in the got a regulatory track, a clinical some of the different types of data past. The growing use of electronic track, a pharmacovigilance track, that are generated and the value that media is particularly interesting and so on. We really want to things they add to the entire knowledge given the Canadian context – to feel different and so we’ve created base of a particular product. Not all Canadian regulations, advertising unique tracks which cut across the data is the same. In this session, we standards, and codes for advertising, traditional disciplines. We’ve taken will examine the different types of and how they all interface together. a different approach this year, and data, their respective strengths and With patients and consumers we’re really interested in getting weaknesses, and how that data is being increasingly informed by feedback from the DIA membership used by different audiences such as and turning to electronic sources and our other attendees. a regulator or a clinician in making for their information, this will decisions about patient care. present an interesting and engaging AH: I’ll go back to your first dialogue about the opportunities and question: If you’re interested in You have served on the challenges that these sources present. participating with DIA in the program committee for future, that’s something that previous DIA Canadian Annual Our “Collaborative Approaches” I would encourage. I found it Meetings. Why do you continue to session will explore some unique to be an enriching experience, serve on the program committee models for collaboration. Because and the opportunity to explore for this meeting? there is increasing interest the many perspectives and in working together through interlinking influences that shape Alice Hui: Last year, I was fortunate collaborative rather than singular the pharmaceutical industry has to join the program committee, approaches, we’ve put this session definitely helped me in my day to but midway through. I found it together to explore how we can day work. It’s an opportunity that’s ■ NORTH AMERICA NORTH to be a very collaborative and create opportunities to deliver worth exploring!

58 GLOBAL FORUM OCTOBER 2011

GR8-Canada Annual Mtg.indd 58 9/19/11 12:15 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

DIA Welcomes New Director for DIA North America

his past July, DIA the International Pharmaceutical products, and other emerging areas, headquarters welcomed Federation. Her numerous honors and that is very appealing to me. T Susan A. Cantrell as the include the 2010 Alliance for first regional regi Director, DIA North Continuing Medical Education Coupled with that, the entire land- America. In this role, Susan will President’s Award. scape of research and development work closely and collaboratively in this industry has changed so dra- with the Advisory Council of North Susan shared these thoughts on the matically within the past few years. America and its Content Advisory opportunities and challenges of serving Clinical trials have gone global. Committee to develop DIA’s overall as DIA’s first Director for North Drug safety in clinical research strategy for this region. She is America with the Global Forum. has become even more important also responsible for outreach to and there is an increased focus on regulatory and other governmental research in the post-marketing set- agencies, and related associations, What most attracted you to ting, including models for compara- and will divide her time between DIA as an organization tive effectiveness research. These DIA worldwide headquarters in through which you can serve the are significant changes and DIA is Horsham, PA, and the newly opened world’s health care communities? helping members deal with those satellite office in Washington, changes by providing a neutral, DC. As a regional director, Susan What attracted me first and fore- global forum where regulators and will also serve on the Global most was the organization’s focus on representatives from industry, aca- Management Team. drug discovery and development. As demia, and clinical practice can all a pharmacist, I am well aware of the come together and talk about these Prior to arriving at DIA, Susan important role that medications oc- issues. That attracted me as well. worked for nearly two decades in a cupy in the delivery of health care to series of progressively responsible patients. More than half of Ameri- positions for the American Society can adults are on at least one pre- You are the first DIA of Health-System Pharmacists, a scription drug and half of our elderly Regional Director for North professional society where she most are on three or more prescription America. What are your responsi- recently served as Vice President drugs. If you were to ask some- bilities and with whom will you of Resources Development,. Prior one if they have taken a prescrip- primarily work? to that, she served as Managing tion medication within the last six Director, ASHP Advantage, months, a very high number would Being the first person hired into a a division of the society that say yes. However, if you were to ask new role is comfortable territory for developed and implemented if they’ve had a surgical or diagnostic me. In my entire career, I have only NORTH AMERICA educational activities to assist procedure, or have been hospitalized been in one job that was vacated by pharmacists and other health care within that same time frame, the another person. Every other position professionals. percentage would be much lower. I have held has been a new posi- So, medications are very important tion. There are both benefits and Susan is a member of the Alliance in US health care, and innovation challenges to that, but I think the for Continuing Medical Education, in medication therapy is critically benefits far outweigh the challenges the American Society of Association important. DIA has expanded its because you have the opportunity Executives, the American Society focus to include companion diag- to assess what needs to be done and of Health-System Pharmacists, and nostics, drug-device combination what your job needs to look like 59

AN2-new Director.indd 59 9/20/11 11:20 AM based on the goals for the organiza- search, especially in the oncology I think the challenge. DIA has such a tion, and can craft it accordingly. area. But my involvement in as- long history of doing excellent work. sociations, both as a volunteer and It’s a very stable organization, even One area of focus will be to establish a staff member, is perhaps the best though, certainly, there have been the North American region with segue into my role here at DIA. some changes over the past few its own DIA identity. We have very years. There’s interest in building well-established regional offices in I was involved as a volunteer leader on some of the successes of the past, Europe and Asia and the organiza- in state and national pharmacy asso- but with the changes in our industry, tion is expanding into Latin America. ciations early in my career. Through there are important new areas My position will focus specifically this involvement, I developed a sense emerging, such as comparative on North America and the needs of for the contributions that volunteers effectiveness research and our members, volunteers, and other can make in professional associations companion diagnostics in medical constituents in this region. I will be and the importance of a professional devices, that we’re focusing on. working closely with the Advisory association in addressing the needs These are things that I haven’t Council for North America, a vol- of its members in their day-to-day focused on extensively, so I am unteer group that provides strategic work. That volunteerism is what interested in learning about those, input to the DIA Board of Directors initially attracted me to association and taking on the challenge of to help us meet the needs of the orga- work. For the past nineteen years, I how we address these emerging nization’s members and customers in have worked in the association world issues. That is one thing I am look- the region and helps build and main- and certainly that has prepared me ing forward to. I like to learn. tain DIA member affiliation within well for the work that we do here at North America. Honing in on the DIA – working with volunteer lead- I had the opportunity during my needs of the constituents we serve ers, looking at the needs of mem- interview process to speak with some in North America and developing bers and constituents, and working of our volunteer leaders, such as the programs and services to meet them to address them. I have been very Chair of our Advisory Council of are major focuses of my position. involved in medical education for North America, a group I’ll be work- members, which is also very compat- ing with extensively. I also had the From a staff perspective, I will be ible with what we do here: Looking at opportunity to interview with some working closely with the other the topics that affect our audiences, of the staff who will be reporting to members of DIA’s Global Manage- assessing their educational needs me. This gave me a good sense of ment Team, which comprises the in regards to those topics, develop- what this organization is all about, other regional directors in Europe, ing content, and designing activities and of the commitment that the China, Japan, and India, as well as and events that meet those needs. volunteer leaders and staff members the executive team in DIA’s global Finally, much of my previous work have in DIA’s future success. That’s headquarters. My position will also has involved strategic alliances and probably the thing I was most involve outreach and liaison activities collaboration with other organiza- excited about: Being part of the with regulatory agencies and other tions. I think all of that translates team here. Seeing the commit- organizations whose priorities and well into what we do here at DIA. ment of the team members and interests are aligned with DIA’s. seeing the excitement about what’s happening here at DIA, What is your educational I just want to be part of that. What previous professional background? experiences will most benefit your service with DIA, and how? I’m a pharmacist by training. After What message would you graduating from pharmacy school, like to deliver to DIA’s Much of my previous experience is I completed a residency in hospital network of members and volun- very compatible with my new role, pharmacy. I have always had a strong teers in North America? and that’s what made me look at this interest in public health and recently position. When I looked at the posi- enrolled in online courses with the DIA is a successful organization tion description, I realized it was very University of North Carolina School with a rich history. The organization closely aligned with most everything of Public Health in order to pursue is focused on meeting the changing that I have done in my career. a Masters’ Degree in Public Health. needs of our members and building upon the guidance provided by our Early in my career as a pharmacist volunteer leaders. We have a strong practicing in an academic medical What opportunities are you leadership team and a succinct vision

NORTH AMERICA NORTH center, I worked extensively with most looking forward to in for the future of the organization. I investigational drugs and re- your new position? am excited to be a part of that. ■ 60 GLOBAL FORUM OCTOBER 2011

AN2-new Director.indd 60 9/20/11 11:20 AM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

DIA Opens Doors: Photo courtesy of St. John’s University Student Poster Presenter to Intern

Michelle Pernice

students tells you, “When I metro into the convention center, I and suffering application issues. This finishfi pharmacy school, I felt…early. I am almost always early was just the type of thing I wanted A wantw to go to law school. and this was surely no exception: to latch onto because it was most IIant want workor in regulatory affairs I was at least an hour early for the amicable to change, the perfect and policy.” What is your reaction? first session. I was also alone and project for a young professional Responses range, exclamations often knew absolutely no one in this to sink her teeth into. The wheels ensue, sometimes questions arise, massive establishment. Although began to turn. It was in the audience and even words of discouragement; not many people were there yet, of a DIA session that I formulated but when I am lucky, advice will just a few friendly DIA employees. the idea for a research project on follow. One of the best words of Nonetheless, I could tell this place implementing REMS. This idea wisdom came two years ago from was built to hold thousands, none served as a talking point throughout Mary Ellen Cosenza of Amgen, Inc., of which I would know. As time the rest of the meeting. If I felt “You should go to DIA next year.” went on and the crowd filled into all the panel was appropriate and the I had just met Dr. Cosenza and did the spaces of the convention center, topic was REMS, I would walk up to not have any notion of what DIA I still felt that I was there early and the microphone, introduce myself stood for, where it would be or how that I was alone, but these feelings as a pharmacy student from St. I could get in. After contacting were quickly becoming signs of John’s University and propose my DIA, I found that students could strength I needed to take advantage idea. I asked if the idea sounded gain access to the entire 46th Annual of. I was early in the sense that I was feasible, if it was already being done DIA Meeting for a very affordable one of the youngest people in each and what the panelists thought rate through application to a student of the sessions I attended. I was of the idea. I received favorable selection committee. I applied as alone, not affiliated with anything responses, helpful tips and fantastic a student pharmacist. Soon, I was or anyone aside from my school. networking opportunities. After the granted access and planned my first These two facts made me free to sessions, my public inquisition led trip as an adult to Washington, DC. speak to anyone regarding essentially to conversations with professionals Before my first day at the meeting, anything I was curious about. The interested to know more about this I planned out which sessions I was sessions were initially over my head idea, and I was able to speak with going to attend and organized a but maintained continuity and them about their work. By the end of calendar with room numbers into common trends, making it easy to these few days, I felt so comfortable a small notebook. I chose a mix learn in succession with each passing approaching people that I even ran of basic and intermediate level meeting. my idea by Janet Woodcock after sessions with one or two advanced the CDER Town Hall meeting on level sessions, considering the I became particularly interested in the final day of the convention. As topic, track and speakers. I was Risk Evaluation Mitigation Strategies a direct result of the conversations looking for pharmacists and lawyers (REMS), a topic with which I was I had at the convention, I was able NORTH AMERICA (especially lawyers with joint not familiar until I had arrived to establish two internships for degrees) presenting regulatory affairs at DIA. The topic of REMS was the summer of 2011. One of the and policy issues. If the speaker was prevalent in a lot of sessions, but the first people to whom I directed my from a company or organization in theme of the conversation was not research proposal is currently my which I was particularly interested, I educational; it was not preaching boss at a summer internship position researched the individual and in what about the established process. at Amgen in Washington, DC. type of work they were involved. Instead, REMS was a developing Another victim of my inquisition Rising up from the underground idea, still victim to a learning curve at DIA will be my preceptor at the

61

GR4-StudentPoster.indd 61 9/21/11 4:40 PM Office of Special Health Issues at As a poster presenter, making 1. Attend the annual meeting. FDA later in the summer. Little did I conversations at sessions came easier know that a short trip to the nation’s as well. Upon engaging a speaker in 2. Get simple business cards made capital would lead to moving down conversation, he will often inquire with your basic contact and school to Washington DC for three months about the poster, where the research information. a year later. The research idea that is going in the future and what I am was born at DIA 2010 learned to looking to do with the information. 3. Get there early mentally (be walk a year later at DIA 2011. At Attending the professional poster innovative) and physically (maybe the 47th Annual DIA Meeting in session on the days following the not an hour early). Chicago, IL I presented Medication student session is insightful. Some of Therapy Management as a Potential the professional research coordinated 4. Come alone. If you have no one Risk Evaluation and Mitigation well with the student topics. Engaging else to talk to, you have nothing to Strategies’ Element: Identifying in conversation with poster presenters lose by approaching a stranger. Benefits and Impediments as a on topics related to my research was student poster presenter. As a poster enlightening and helped inspire ideas 5. Create short-term goals that seem presenter networking opportunities for future evolution of the project. As almost unattainable and long- are boundless. Recruiters approach a student who has truly benefitted term goals that seem impossible. students throughout the day from DIA and plans to maintain Discuss these at the convention. and students are able to make involvement throughout my career, I You will achieve the short-term conversation about what they are offer advice for students considering goals and refine the long-term most passionate: the research. getting involved with DIA. goals. ■ NORTH AMERICA NORTH

62 GLOBAL FORUM OCTOBER 2011

GR4-StudentPoster.indd 62 9/21/11 4:40 PM DIA 2012 Collaborate to Innovate June 24-28, 2012 Pennsylvania Convention Center Philadelphia, PA

PROGRAM CHAIR Craig H. Lipset DIA 2012 Head of Clinical Innovation Worldwide Research & Development Pfizer, Inc. Collaborate to Innovate

FEATURES • Preconference Tutorials and Interactive Workshops • Expert Panels and Presentations • Knowledgeable Thought Leaders in the Industry • Global Regulatory Agencies • Student and Professional Poster Presentations • Multi-track Plenary Sessions • Executive Sessions • Special Interest Area Community (SIAC) Sessions

SHOWCASE AND ACTIVITIES • Networking Events and Lunches • One of the Industry’s Largest Exhibit Halls DIA 2012 is the largest multidisciplinary event that brings together a global network of professionals to foster innovation that will lead to the development of safe and effective health care products. CALL FOR POSTERS! Call for Professional Posters Now Open! SUBMISSION DEADLINE: THURSDAY, FEBRUARY 16, 2012 Accelerate Your Business Goals Showcase your products and services to say 7,000+ professionals involved in the discovery, Call for Student Posters Now Open! development, and life cycle management of pharmaceuticals, biotechnology, medical devices, SUBMISSION DEADLINE: and related health care products. MONDAY, MARCH 5, 2012 | To exhibit at DIA 2012, contact [email protected], or +1.215.442.6100

DIA 2012 AVAILABLE TRACKS TRACK 01 Clinical Operations REGISTER NOW TRACK 02 Project/Portfolio Management and Strategic Planning TRACK 03 Innovative Partnering Models and Outsourcing Strategies TRACK 04 Nonclinical and Translational Development/Early Phase Clinical Development AND SAVE! TRACK 05 Product Advertising and Marketing TRACK 06 Medical Writing and Medical Communications TRACK 07 Processes and Technologies for Clinical Research TRACK 08 Regulatory Affairs and Submissions REGISTRATION TRACK 09 Medical Diagnostics and Devices MEMBER STANDARD* TRACK 10 Public Policy/Health Care Compliance/Regulatory Law Registered on or before Dec. 31, 2011 ...... $1250 TRACK 11 Compliance to Good Clinical Practice (GCP), Good Laboratory Practice (GLP), and Quality Registered on or before Feb. 29, 2012 ...... $1300 Assurance (QA) Registered after Feb. 29, 2012 ...... $1350 TRACK 12 Pharmaceutical Quality NONMEMBER STANDARD ...... $1490 TRACK 13 Health Economics and Outcomes (HEO)/Comparative Effectiveness Research (CER)/Health GOVERNMENT MEMBER ...... $480 Technology Assessment (HTA) GOVERNMENT NONMEMBER ...... $620 TRACK 14 Clinical Safety and Pharmacovigilance CHARITABLE NONPROFIT/ TRACK 15 Statistical Science and Quantitative Thinking ACADEMIA MEMBER ...... $875 TRACK 16 Professional Development CHARITABLE NONPROFIT/ TRACK 17 Global Regulatory ACADEMIA NONMEMBER ...... $1015 STUDENTS** ...... $250

*Early-bird discount available on nondiscount member standard fee only. ** For student rate application form contact: Visit www.diahome.org/dia2012/gf for up-to-the-minute information. Donna Mayer | +1.215.293.5817 | [email protected]

GR4-StudentPoster.indd 63 9/21/11 4:40 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 ON LOCATION: OTTAWA ON LOCATION:

64

Ottawa.indd 64 9/21/11 3:07 PM OTTAWA CANADA’s SHOWCASE TO THE WORLD

ttawa’st skyline, dominated by its old- Socially, it is also infused with countless cultural, worldw style Parliamentary buildings and tourist, and recreational activities, as well as an O museums,m belies the reality of industry eclectic restaurant and active club scene. Founded in tthehe ccityity today. The city, which derives its name in 1855, Ottawa is the capital of Canada and is from an Algonquian fur-trapping tribe, boasts a located on the banks of the Ottawa, Rideau and myriad of research, med-tech and modern-tech Gatineau rivers. Canada’s fourth-largest city is a companies, earning it the designation of “Silicon complementary blend of urban and rural lifestyles, Valley of the North.” old and new neighborhoods, culture and heritage, business and government. Ottawa also has a Ottawa’s business and employment opportunities high standard of living reflected in a multitude of draw a wide range of people to a variety of jobs. accessible services, vibrant entertainment, exciting From advanced technology, to government, recreational activities, and thriving businesses. research and development, health, education and Ottawa-Gatineau is positioned to market and to trades, the workforce contributes to both the local celebrate the region’s distinctiveness, not only as and global economies. the nation’s capital, but The city’s academic as a cultural capital foundations -- from with a unique heritage, its strong public a distinct Aboriginal school system to peoples’ history and a universities, colleges vibrant identity. Ottawa and R&D centers is home to a UNESCO of excellence -- World Heritage Site contribute to Ottawa (Rideau Canal); a vital having the highest and bilingual local arts educated workforce and heritage scene; in Canada. A bright exceptional festivals, workforce, according Parliament reflected in a downtown office building fairs, and events; to the Ottawa city website, “is a key foundation for diverse cultural neighborhoods; historic rural a smart city and business success.” communities; and robust offerings of local foods and culinary experiences. Their residents are among the most highly educated in Canada with over 60% holding a post- Ottawa is a “Bright City”. It is one of the world’s secondary degree, certificate or college diploma safest and most beautiful communities in which ON LOCATION: OTTAWA and that, combined with the fact that over half to live, work, learn, play, and raise a family. The of its 912,000 residents are under the age of 38, city prides itself on its quality of life. It is home make Ottawa a city with endless vitality and an to a wide range of age groups from families with abundance of opportunity in technology and children to adult professionals to university business. There are approximately 522,000 jobs students and senior citizens. As a G8 capital city, in Ottawa and the major sectors of employment Ottawa is Canada’s showcase city to the world. It is according to the most recent Employment endowed with a number of national museums and Survey are advanced technology (68,000), federal performing arts institutions. The city is graced with government (103,000), health and education a civic design that places high priority on green (79,000), and trade (61,000). spaces, parklands and trails, making Ottawa a bright and beautiful landscape for all to enjoy.

VOL 3 ISSUE 5 GLOBAL FORUM 65

Ottawa.indd 65 9/21/11 3:07 PM Getting Around Town You can easily walk around Ottawa. A car is unnecessary except for the most distant attractions. When on foot, know on which side of the Rideau Canal you are. The canal divides downtown into “west of the canal” (Centretown) and “east of the canal” (Lowertown). On the west Getting Here, Getting Around side you will find Parliament Hill, Those flying into Ottawa will land the Canadian War Museum, and the at the Ottawa Macdonald-Cartier Canadian Museum of Nature; while International Airport (YOW) and on the east side, for example, you have several options for reaching the can explore the Fairmont Château Ottawa downtown hotels. Laurier and ByWard Market.

Airport Shuttle Driving in Ottawa The YOW Airporter Shuttle departs While traffic is fairly light, driving from Post 10 just outside the airport’s here can be difficult. One-way Level 1 Arrivals area. Transport to streets, blocked residential streets, a downtown hotel is $15 per person and streets that change names or one-way or $25 per person roundtrip come to an abrupt dead end can (www.yowshuttle.com). If you opt for make driving challenging. Pay a taxi to your hotel instead, expect attention to the color-coded parking to pay around $29. (Prices subject to meters: gray (one hour), green (two change.) hours), and yellow (tour buses only). The meters accept prepaid parking Public Transportation cards or coins, but be sure to read Canadian and Ottawan flags You can familiarize yourself with the the signs for any parking restrictions. gelato, fresh pasta, or a fabulous routes and bus stops of OC Transpo If you prefer the municipal parking four-course meal with wine. Don’t by visiting www.octranspo.com. lots, look for signs with a white letter miss the shops here and the beautiful Day passes can be bought at vendor P in a green circle. mural on Preston Street that depicts locations throughout the city or on Italian life in Ottawa. the bus. Bus operators cannot make Local Color change; so always carry the exact Like most cosmopolitan cities, a Downtown is in the center of fare. The O-Train is Ottawa’s local century of immigration has flavored Ottawa. It’s where you’ll find light rail rapid transit train. Tickets Ottawa with an ethnic diversity Parliament Hill, the Peace Tower, can be purchased at the station and a multicultural palette of and the historic Rideau Canal’s platform. Visit www.ottawalightrail. neighborhoods. Each has its own working locks. Or you can walk ca for more information. ambiance, cuisine, architecture, and through the upscale shops at the shops. For a taste of Asian culture, Sparks Street Mall and the majestic Ottawa can be accessed by four you can explore Ottawa’s Chinatown Fairmont Chateau Laurier hotel. main waterways: the Ottawa River where you will find delicious foods There is plenty to see and do and (flowing into the St. Lawrence River), from Vietnam, China, Korea, and it’s all within a few blocks of the the Rideau River (flowing into the Thailand. It is located just west of hotel area. Ottawa River), the Gatineau River Downtown in the Somerset Heights (flowing into the Ottawa River) area. Looking for a unique shopping and the Rideau Canal (linking Lake experience? Check out the four- Ontario at Kingston to the Ottawa Find Preston Street, also known square-block ByWard Market River). For directions by boat, please as Corso Italia, and you’ll discover district not far from Parliament Hill; visit the Friends of the Rideau Ottawa’s Little Italy neighborhood. established in 1826 by Lt. Col. John

ON LOCATION: OTTAWA ON LOCATION: website. Here, day or night, you can enjoy By, today the area offers museums,

66 GLOBAL FORUM OCTOBER 2011

Ottawa.indd 66 9/21/11 3:07 PM cafes, specialty food shops, boutiques, galleries, and some trendy nightspots. Bordered by Clarence, York, Murray, and George streets, here you will find some of Ottawa’s best restaurants and many one- of-a-kind shops selling handmade crafts, distinctive jewelry, fashionable clothing, and great souvenirs. With its quaint cobblestone courtyards and alleyways, the ByWard Market area is a great place to live, shop, and dine.

Along Sussex Drive, you’ll discover Rideau Canal the National Gallery of Canada and Majors Hill Park. Continue galleries displaying the works of local skating as a fresh-air commute to on Sussex Drive, and you’ll head artists, or unwind at a café or pub. work or school. into the Rockcliffe area where stately homes, magnificent gardens, In spring and summer, the walkways For visitors, Parliament Hill attracts beautiful Rockcliffe Park, and some alongside the Rideau Canal are attention, but there are also plenty of spectacular views await you. You’ll bustling with the perpetual motion museums, parks, golf courses, public pass the residences of ambassadors of bikers and joggers while its tennis clubs, and even live music and international dignitaries as well waterways serve as a playground for and theatre to enjoy. You can take as the homes of Canada’s Prime recreational boaters and tourists. a hot-air balloon ride year round, Minister and the Governor General. Meanwhile, from January to March test your luck at the Casino du Lac- the Rideau Canal turns into a frozen Leamy in nearby Gatineau, see an Just south of Ottawa on the Rideau arena where annually a million or Ottawa Senators hockey game, or River you can sit back and relax in more skaters glide along the world’s stay in town and shop the boutiques the historic waterfront village of largest outdoor “skating rink,” of the ByWard Market area. There’s Manotick. Visit Watson’s Mill, a equivalent in size to 90 Olympic- no shortage of late-night clubs, working gristmill and learn of its sized ice rinks. Not only used for restaurants, and bars –visit www. history and resident ghost, stroll recreational sport, many health- ottawaxpress.ca for events while you through quaint boutiques and conscious Ottawa residents chose are visting.

ByWard Market ON LOCATION: OTTAWA

VOL 3 ISSUE 5 GLOBAL FORUM 67

Ottawa.indd 67 9/21/11 3:07 PM See what life was like in Ottawa in located amidst 79 acres of beautiful is located on the corner of Sussex the late 19th century. The Laurier woods and gardens, has served as Drive between St. Patrick Street House (www.pc.gc.ca/laurierhouse; the private residence and workplace and Guigues Avenue, in front of 613-992-8142; 335 Laurier Avenue of Canadian governor-generals since the National Gallery of Canada. East), a National Historic Site, 1867. This statesman carries out The spacious and visually appealing portrays Victorian style architecture the royal and ceremonial functions interior of the late Victorian-style and contains items and furniture on behalf of the Queen of England, Roman Catholic cathedral features from influential prime ministers. amidst an opulent 19th-century two large vaulted ceilings, carved interior. mahogany woodwork, and stained- Rideau Canal 613-234-4570) can be glass windows, created by artist accessed by descending a staircase The Royal Canadian Mint (www. Guido Nincheri. They depict scenes at Wellington Street between the mint.ca; 613-993-8990 or 800-276- from the lives of Jesus and the Virgin Château Laurier and the Parliament 7714; 320 Sussex Drive) is where Mary and were installed between Building. Get a close-up view of the commemorative and numismatic 1956 and 1961 to replace seventeen last lock of the Rideau Canal that (collector) coins are designed, original windows. once served as a military fortification minted, and hand-engraved. Tour and a commercial waterway. reservations are required but a No visit to the seat of the Canadian wonderful exhibit about the history government would be complete Bytown Museum (www. of modern money, in the new wing of without stopping by Ottawa’s bytownmuseum.com) is the oldest this 1908 stone building, makes the Parliament Hill on Wellington stone building in Ottawa and visit especially worthwhile. Street which consists of the center, provides a pleasant overview of the east and west blocks. city that got its start as the small Don’t be fooled by the unremarkable settlement called Bytown. exterior of Ottawa’s oldest church. The Center Block includes the Built between 1841 and the 1880’s, original Parliamentary Library and The magnificent structure of Rideau the Notre Dame Cathedral the House of Parliament which Hall (www.gg.ca; 800-465-6890; Basilica (www.notredameottawa. was erected in 1920. The latter is a 613-993-8200; 1 Sussex Drive) is com; 631-241-7496; 385 Sussex Dr) wonderful example of neo-Gothic

DID YOU KNOW?

t
The time zone is Eastern Daylight t
Tipping of 10%-15% at restaurants t
Ottawa is the home of the Time (EDT) through November is standard; exceptional service, Government of Canada: 6th, then Eastern Standard Time 20%; taxis, 10%. Parliament, the Senate, and the (EST). Supreme Court of Canada. t
Ottawa’s total land area is 2,796 t
When making an international square kilometers or 1,080 square t
Ottawa has more engineers, phone call, dial 1 for the miles, 90 kilometers east to west scientists and PhD graduates per international country code and and it is almost 80% rural. capita than any other city in the (613) for the area code. country. t
In a survey conducted by Mercer t
English and French are spoken Human Resources International t
The legal drinking age is 19 years widely throughout Ottawa. of 200 cities worldwide for best of age or older with a photo I.D. quality of life, Ottawa ranks 18th. t
Average temperature in late t
Cuisine, service and quality October is 59⁰F. t
Ottawa ranks 90th out of 144 reviews of local Ottawa international cities on the list of restaurants can be found at www. t
Call 911 for police, fire or most expensive cities making it restaurantthing.com/ca/on/ottawa ambulance. one of the more affordable cities and www.ottawafoodies.com. in which to live.

ON LOCATION: OTTAWA ON LOCATION: t
Electricity is 110 to 120 volts AC.

68 GLOBAL FORUM OCTOBER 2011

Ottawa.indd 68 9/21/11 3:07 PM The West Block contains The Canadian Museum of Parliamentary offices, administrative Civilization (www.civilization. space, and meeting rooms that are ca; 800-555-5621; 100 Laurier St., not open to the public. Gatineau) which is located across the river in Gatineau is probably Tours: General tours of Parliament one of Canada’s most popular are available year-round. To find museums. It includes information out more information visit the about the country’s significant website: http://www2.parl.gc.ca/ historical figures, its geography, Sites/LOP/Visitors/index-e. and its aboriginal inhabitants. asp#visitor. To view proceedings In the cavernous Canada Hall, of Parliament, or to see if either reconstructed, life-size settings the House or Senate is in session, represent various periods in go to www.parl.gc.ca or call Canadian history. The Canadian 866-599-4999. Postal Museum, an IMAX theater, and the Canadian Children’s Museum Walking west of the Parliament are also located within this facility. buildings, you’ll view the Supreme Designed by award-winning architect Court of Canada. This building Douglas Cardinal, a native Canadian, replaced the Old Supreme Court the exterior curves in the design of Canadian Mounties which was built in 1889 and was torn the building are said to be symbolic down in 1945. of the forces of nature. Revival architecture and features sixteen sides, pointed arches, Ottawa’s Museums Learn more about animal life, plant buttresses and contrasting stone Ottawa has over 30 interesting life, and the environment at the work. It replaced the original house museums and more than 50 galleries; of Parliament, which was destroyed below are a few of the most popular Canadian Museum of Nature (www. in the fire of 1916. venues. nature.ca; 800-263-4433 or 613-566-

Also within the Center Block are the:

Peace Tower which was erected in 1927 to honor Canada’s WWI Ottawa: soldiers Global Technology Center With more engineers, scientists Ottawa-Gatineau has been Centennial Flame, a natural gas and PhD graduates per capita consistently selected by the flame within a fountain, lit in 1967 to than any other city in Canada, Intelligent Community Forum as commemorate the country’s 100th Ottawa is home to more than 1800 one of the world’s most intelligent birthday advanced technology companies communities and one of the including: Nortel Networks, Cisco world’s top five sites for R&D. ON LOCATION: OTTAWA Statues of prime ministers, Canadian Systems, Dell and ING Direct. Ottawa leads the way for research confederation founders, and Queen Ottawa is a thriving R&D, clinical and innovation. It’s also home to Elizabeth II research, and manufacturing HealthCanada, a government-run center. Institutions here are organization that helps Canadians Original Victoria Tower bell which conducting stem cell research maintain and improve their health. was retrieved after the fire of 1916 and demonstrating world-class The ultimate goal of HealthCanada strengths in genomics, proteomics, is to make Canada the healthiest The East Block has four historic immunotherapeutics, and country in the world “as measured rooms portraying different regenerative medicine. by longevity, lifestyle, and effective historic periods, including the use of the public healthcare original governor-general’s office system.” representing 1872–1878.

VOL 3 ISSUE 5 GLOBAL FORUM 69

Ottawa.indd 69 9/21/11 3:07 PM Famer Louis Cochand, as well as a badge from the “Crazy Canuks” ski team who achieved top-ten recognition at the World Cup in 1974.

The Canadian War Museum (www.warmuseum.ca; 800-555- 5621 or 819-776-8600; 1Vimy Place) presents the entire military history of Canada from its inception by European settlers. Eight permanent exhibits reflect military conflicts through personal recollections, art, and photography and by portraying actual military experiences, such as a National Gallery of Canada recreated trench that makes you feel as if you are on an actual battlefield. 4700; 240 McLeod Street). Observe how commercial canoes became A single window in the museum’s specimens of native wildlife such profitable enough to become a Memorial Hall provides a view of as bison and moose; visit the fossil symbol of Canada. View a model the Peace Tower located east on gallery and learn about dinosaurs of the Advance CANDU Reactor Parliament Hill. or take a walk through the bird to learn about Canada’s advances gallery where hundreds of varieties in generating nuclear power. Plus, The National Gallery of Canada of birds are on display. Watch lively explore through videos, interactive (www.national.gallery.ca; 800-319- nature documentaries and enjoy the displays and games in the Connext 2787 or 613-990-1985; 380 Sussex well-reputed dioramas of Canadian exhibit how messages travel through Drive) contains 800 examples of mammals painted by Manitoba artist a digital network. Don’t miss the sculptures, paintings and decorative Clarence Tillenius. exciting Canada in Space exhibit art; included are the Canadian In a recent renovation, one new in which visitors are “launched” in a wilderness landscape paintings of exhibit explores the vital role that rocket ship on a simulated mission to Tom Thomson and his affiliated water plays in sustaining freshwater save a colony on Mars! artists known as “The Group of and marine habitats, as well as Seven,” as well as A.Y. Jackson’s human life. Learn all about the history of skiing, famous painting “The Red Maple.” its evolution, and its influence on Inuit prints and sculptures from The Canada Science and Canadian culture at the Canadian soapstone and whalebones also make Technology Museum (www. Ski Museum (www.skimuseum.ca; interesting viewing. Or see works by sciencetech.technomuses.ca; 613- 613-722-3584; 960 Scott Street). See Chagall and Picasso, as well as pop 991-3044; 1867 St. Laurent Blvd) is early handmade wooden and seal art and minimalism. You can also highly interactive and fun for kids as skin skis and other artifacts, as well view the remains of the 1888 neo- well as adults. Jump aboard a steam as commemorative items from the Gothic Convent of Our Lady of the locomotive, learn about leading country’s heroes of the sport. This Sacred Heart. It is the only one of its Canadian inventors, or discover includes the 1936 trophy of Hall of kind in North America. ■

Many thanks to the Ottawa Tourism Board and the official Ottawa travel website,

ON LOCATION: OTTAWA ON LOCATION: www.ottawatourism.ca where much of this information was found.

70 GLOBAL FORUM OCTOBER 2011

Ottawa.indd 70 9/21/11 3:08 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

12th Conference on European Electronic Document Management (eDM)

New Practices beyond Document Management

IA has always been in the documentation landscape moves forefront of new ideas and from a state of pure separation D technologies and at next between data and text towards Conference Program month’s Electronic Document hybrid forms combining these two Co-chairs Management (eDM) conference in formats, our industry faces new Zurich will once again lead the way opportunities and new challenges,” Dimitri Stamatiadis, by offering a privileged forum for he said. As a result, pharmaceutical Director Management Processes, discussing, understanding, and professionals must revise their views Merck Serono, Switzerland addressing the new challenges in and practices and gradually move information management. from traditional data and document Hans van Bruggen, management to information and Senior Regulatory Affairs For the past few decades, as the content management. Consultant, eCTDconsultancy, industry moved from paper-based The Netherlands. content to electronic files, there has DIA will help drive that change been a clear distinction between at the eDM conference, which Conference documents and data, and the context will take place from November Programme Committee in which this content was used. 30 to December 2 in Zurich. This Data was managed in structured Thomas Altenwerth, annual event draws not only on the databases, analyzed, then transferred Head of Global Regulatory Affairs experience of record management, manually, and documents were Archives Wuppertal, Bayer data management, and eDiscovery recreated over and over again and HealthCare Pharmaceuticals, in the financial industry. It also stored in Electronic Document Germany examines submissions in a global Management (eDM) systems. Today this separation is slowly disappearing environment and will provide Melanie J. Clare, Global Head, as new technologies such as pertinent updates from several Clinical Document Management & Extensible Mark-up Language (XML) regulatory agencies. In addition, Publishing, GlaxoSmithKline, USA bring documents, data, and other delegates will be able to join in forms of information together in one and contribute to roundtable Joris Kampmeijer, Head of melting pot. This welcome evolution discussions on regulatory operations Information Processing, Medicines opens new perspectives in such and Electronic Trial Master Evaluation Board, areas as collaboration, reuse, review, Files (eTMFs). Later sessions The Netherlands analysis, and records management. will cover registration tracking, Clinical Research Organizations, Anita Paul, Head of Corporate Dr. Dimitri Stamatiadis, conference Implementation of Regulatory Records Management, F. Co-chair and Director of Information Submission Standards Hoffmann-La Roche AG, Management Processes, Merck (IRISS), Darwin Information Switzerland

Serono, Switzerland, is clear about Typing Architecture (DITA), and EUROPE the value of the meeting. “As the eSignatures. ■

Early–bird rates are available for members. Register by October 18 and save EUR200. Reference event 11104. We look forward to seeing you there. 71

GR2- eDM.indd 71 9/20/11 3:45 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

DIA Europe Presents QRM Conference

uality Risk Management the efficiency of clinical drug Quality Risk Management- (QRM) is a process for development. Safety Science, F. Hoffmann- Q identifying quality-related La Roche Ltd., Switzerland; hazards associated with a On November 10 - 11, DIA Europe Dr. Beat E. Widler, Clinical product, estimating and evaluating will present our Quality Risk Quality and Risk Management the associated risks, controlling these Management in Clinical Drug expert, Zug, Switzerland; and risks, and monitoring the Development Conference 2011 in Dr. Peter Schiemann, Quality effectiveness of the control. Effective Berlin, Germany. The purpose of Risk Management expert, Basel, quality risk management ensures the this conference is to share industry Switzerland. high quality of drug product for the and regulators’ experience in the patient. The FDA has been What is QRM? particularly active in fostering this concept - FDA’s Quality by Design EffectiveEffeEffecc quality Quality Risk Management (QRM) (QbD) initiative emphasises building is first of all a cultural mind-set that quality into a product during risk management supports a process for identifying development rather than attempting “ quality-related hazards or deviations to “test” quality into a product ensures a high from expected standards or retrospectively. specifications associated with a quality of drug product or an output, estimating Recently the application of the QRM/ and evaluating the associated QdD approach has been expanding product for risks, controlling these risks, and to clinical drug development as the patient.nnt.t. monitoring the effectiveness of the a means of enhancing work in control. highly regulated areas such as GCP compliance, data integrity, and How will QRM impact patient safety and protection. The application of QRM/QbD” to the drug development? How natural further evolution would be entire spectrum of clinical drug will patients benefit from QRM? to examine the potential of such a development. The goal is to increase systematic risk-based approach to the accessibility of such experience Effective quality risk management support other activities of clinical and to stimulate its wider use. ensures the high quality of drug drug development such as decision- product for the patient. The FDA has making, planning and contingency The following Q&A compiles been particularly active in fostering planning, and proactive project thoughts on these topics this concept - FDA's Quality by de-risking, where there would be from conference Co-chairs Design (QbD) initiative emphasises obvious advantages in optimizing Barbara Leishman, Head, building quality into a product EUROPE

72

GR3-Europe QRM.indd 72 9/19/11 12:19 PM 73 EUROPE 9/19/11 12:19 PM

GLOBAL FORUM GLOBAL ■ November 10-11 How willHow delegates benefit from attending the Management in Clinical Drug Berlin,Germany "Quality Risk Development” Conference 2011 November 2011 QRM conference Berlin? in The purpose of this conference is The purposeconference this of industry share to and regulators' of application in the experience spectrumQRM/QbD entire the to of clinical drug development. The increasegoal of is to accessibility the its stimulate and to such experience wider use. The combination of carefulcombination The planning and pre-defined controls gives milestone deliverables at patients that assurance to participating in a clinical trial is not a compound with a novel risky undertaking because undesired deviations from the clinical research plan can be systematically identified and corrected an accident before happens. 5 3 ISSUE VOL How establishedHow is QRM in drug development? QRM already well and QbD are established in areas such as manufacturing and are characterized process by strong dependency and precise quality specifications deliverables. for pharmaceutical in the date, To has been there industry, less of these principlesapplication in activities such as clinical drug development. Theseto tend be based on data-driven, iterative decision-making processes, complex multi-factorial and external internal influences, and experience, human expert judgment. The principal benefits of establishing effective QRM processes fact include the that QRM principles can be applied Medicines bothto international and Regulatory (MRA’s) Authorities pharmaceutical manufacturers. In addition, science-based decision- making can be embedded into resources canpractice, be focused on risks patients, to restrictive and unnecessary practices can both that be avoided, and, finally, and transparencycommunication benefit. What are the benefitsWhat of establishing effective QRM processes? of application the Recently, QRM/QbDthe has approach been clinicalto drug expanding development as a means of in highly regulated enhancing work areas as such GCP The compliance. integrity data as ensure aim is to as safety and protectionwell patient proactive planning of through clinicalthe trial activities and of “smart” implementation the This allows identification controls. and earlycorrection of deviations plannedfrom the design study and implementation. The logical would step to be next of such a potential the examine systematic risk-based approach supportto clinical other drug development activities. These include portfolio decision-making, planning and contingency planning, and proactive project de-risking. Here would bethere obvious advantages efficiencyin optimising the clinical of drug development. during development rather than than during development rather a quality into "test" to attempting product retrospectively. GR3-Europe QRM.indd 73 GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

Q&A with New ACC Chair

r. Ning Xu, new Chair of study sites management, and quality At our recent Annual Meeting in the DIA Advisory Council control. Phase 1, first in human stud- China, we covered a lot of these D of China (ACC), has many ies, is a hot topic in China right now. topics and received very positive yearsears of clclinical research experience Also, the model of working with a feedback from our attendees. Next in both the pharmaceutical and CRO CRO – how to plan and monitor the year, we may talk about new top- industries. He currently serves as project, and get results – what is the ics, such as medical devices and Executive Director, Head of Clinical best model of working with CROs? diagnostics. We’re trying to get Development Service, for Covance Drug safety and pharmacovigilance more investigators involved, so China. Dr. Xu has worked as Medical are also important topics. We’ve re- we hope to include more subjects Director for such pharmaceutical cently had more people talking about initiated by investigators such as companies as J&J and GSK, and CMC – chemistry, manufacturing & IRBs, site resource management, has also served as Executive Vice control – and API – active pharma- and how industry and CROs and President for Excel PharmaStudies ceutical ingredients; post-marketing investigators can work together. and of Senior Clinical Research for studies and pharmacovigilance of Parexel in the US. marketed products. There are a lot of hot topics from the clinical side. How does your nation’s Dr. Xu earned his MD from Peking industry, regulatory, and Union Medical College. He worked From the regulatory perspective, social environments make the DIA as a pulmonary physician in Beijing the regulatory approval timeline is member and volunteer experience Union Hospital for six years before the biggest issue in China. It’s a very in China unique? completing his postdoctoral lengthy process which, for a new fellowship at the Medical School, drug, can take eight to ten months– China does have its own unique University of Illinois at Chicago, nearly one year. The regulatory culture and way of working with investigating neutrophil inhibitory approval timeline is always a very people. When we develop a drug in factor in preventing acute lung hot topic at our conferences. People China as part of a global trial, we are injury. He subsequently received his would like to hear SFDA officials facing several challenges. Participat- MBA from the University of Illinois explain how they can improve the ing in our DIA platform allows you at Chicago. Dr. Xu spoke with the approval timeline. Regulations for to learn about not just the topics of Global Forum about the challenges biological products in China are which we just spoke, but about is- and opportunities he foresees in his even more complicated than for sues that are more related to culture new DIA volunteer role as Chair of chemical drugs. While quite differ- and people. How do you manage the ACC. ent from other biological products, your staff and your clinical team vaccines are considered part of in China? What are the ways that them, and are also being discussed. Chinese people communicate with What are some of the each other? What is their working current “industry hot People wish to talk about how to style? What are their needs and con- topics” in China from the scientific leverage the data from China in cerns? These can be quite different. perspective? From the regulatory global studies. There’s a big pa- perspective? tient pool, so we talk about how For example, I believe that American China plays both a regional and a people are more direct when they From the scientific perspective, there global role in drug development: communicate, such as an employee are a lot of clinical trial “hot topics” What are the opportunities and discussing their professional progress from the perspective of clinical oper- challenges? What real case experi- with their manager. Americans are

CHINA ation productivity, staff management, ences can we share with others? very comfortable expressing their

74

GR10-China.indd 74 9/19/11 3:17 PM Dr. Ning Xu

professionals who have Doctorate or come to China to deliver the train- career development needs; in China, Master’s degrees from their medical ing, it’s mostly delivered in English, employees don’t raise this issue but school or pharmacy school. How- not Chinese. DIA conducts several expect their manager to talk to them ever, we lack experienced talents. workshops and training programs about it, and they still may not an- There is a huge need for training in China, and most of these pro- swer your question directly. In China, in China, both for industry and grams are in English. Although the they can try to describe things in a investigators, on clinical research. trainer is very experienced and clear, complicated way that’s not so direct. There is a large need for training students do not understand one investigators on how to conduct and hundred percent – they understand It’s also good to remember that manage clinical trials according to maybe eighty percent. How can we China is the fastest growing mar- recognized ICH GCP standards. overcome the language barrier? ket, and not just for pharmaceuti- cals. Most pharma companies and In China, every hospital has an CROs are expanding their teams IRB, but when each conducts their What message would you in China but, the fact is, we do not work, their criteria and standard like to deliver to our DIA have enough experienced talent. procedures may have differences. volunteers and members in China? Employee recruitment and reten- Some may be too strict, while tion are big issues: What are the others may not be strict enough, As a volunteer, five to ten years ways to promote people and identify about study design and the evalu- from now, you will see more value paths for career advancement in ation of patients’ benefits. in what you do for DIA today. China? It could be different in China DIA provides a good platform for compared to the western world. Professionals are trained by the people to share information and sponsor at the investigators’ meet- experiences, to network and to If you want to build development in ing, but that’s very limited and very build ways that help patients China, you need to think about how basic. At the moment, we need more improve their lives. This is the to communicate with and how to training to help investigators deal reason why I’ve spent several years manage Chinese people. Of course, with complicated issues and how to volunteering and working with it’s inevitable that you’ve got to in- manage a study from a higher level, DIA. Now I get to assume the teract with government officials who especially more complex studies. responsibilities of the Chair of the have their own, very unique way, of ACC, and help DIA deliver more working with others. Relationships DIA as a non-profit organization is knowledge and experience to China. are important in China, especially neutral, and we have a lot of training At the same time, we would also how you establish your relation- materials. But we need to identify the like to use this platform to share ships with government officials. real needs of different constituents in our knowledge and experience with China: government officials, investi- other DIA members all over the gators, others in industry. There are world. DIA is still small and relatively What specific scientific, a lot of opportunities. Also, if we’re young in China. We started from industry, or regulatory disci- going to deliver training, we’d bet- small things, but if we keep doing plines could DIA help advance the ter deliver that training in Chinese. small things, we end up doing very most in China through our educa- We do not have a lot of good train- big things. I believe that what we do

tional offerings? ers who can speak Mandarin, for today will create bigger value years CHINA example. We lack locally-trained from now because we are creating In China, we have a large talent pool trainers. Although we can take and building up our platform in that has many well-educated young global materials and ask people to China. ■

VOL 3 ISSUE 5 GLOBAL FORUM 75

GR10-China.indd 75 9/19/11 3:17 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 DIA & SAMEFA TEAM

for 8th Latin

American

Congress

n tandem with DIA’s expanded Sabban, SAMEFA President, serves and a Latin American regulatory vision for Latin America, as Scientific Committee Chair. affairs update. I formalized with the recent Attendees will be welcomed to the formation of a new, provisional Congress by Dr. Groppa and by Dr. Groppa will chair the concluding Advisory Council of Latin America, Paul Pomerantz, DIA Worldwide roundtable on educational options DIA will return to Argentina for our Executive Director. After their in clinical research in Latin America. 8th Latin American Congress on welcome, the first plenary session He shared these thoughts about this Clinical Research at the will address adult mesenchymal stem roundtable session, this Congress, Panamericano Hotel and Resort in cells and feature Arnold Caplan, and its importance to Latin America. Buenos Aires, from October 19 – 21. Director, Skeletal Research Center, th DIA previously presented our 5 and Professor of Biology & General You previously served as Latin American Congress of Clinical Medical Sciences, Case Western SAMEFA President. How Research in Buenos Aires, in 2008. can organizations such as DIA help Reserve University. SAMEFA contribute to better Subtitled Latin America Role in patient care in Latin America? The second plenary session will Worldwide Clinical Research, present roundtable discussion this Congress is co-sponsored by I think that continuing education of medical device clinical trials, SAMEFA and will offer simultaneous among health professionals is the English, Portuguese, and Spanish co-chaired by Dr. Sabban and right way to do it. Also, it’s necessary translation. It will be preceded Marcelo Vianna de Lima, Medical to approach professionals with by two tutorials, on Risk Project Director, Latin America – Medical experience in this discipline from Management and Clinical Quality Diagnostics, GE Healthcare Brazil. developed countries, so they can Assurance: The Basics, on The Congress will, thereafter, show what has happened in their own October 19. proceed through several similarly clinical investigations. We put that structured roundtable discussion experience together with that which Dr. Juan Carlos Groppa, MD, Past sessions on biosimilars, marketing is observed and manifest in each President of the Argentine Society application data quality, regional Latin American country, following of Pharmaceutical Medicine logistics, clinical research endpoints international standards and according (SAMEFA), serves as Congress and surrogates, clinical safety and the proper respect to each patient, to Chairperson. Dr. Hugo Cohen pharmacovigilance, ethical issues, help improve our patient care. LATIN AMERICA LATIN

76

GR5-Latin America.indd 76 9/19/11 3:31 PM important event with both national care professions. It’s necessary to give Are there historical, social, and international transcendence. I a good education to all who impact or cultural aspects that think that it is necessary to maintain and act in the therapeutic interest present unique challenges to a continuity and actualization about of millions of patients around the clinical research and drug the different and most important world. Our main goal must be to take development? topics for clinical investigators care of and respect the patient above working within clinical research all things. Argentina is a multicultural and drug development, which country with a huge European this Congress must address. For That’s why this roundtable session immigrant population, with unique professionals with an important characteristics in different parts career trajectory in this activity, is necessary: To show in detail the of the country. But its scientific participating in this Congress different academic and professional and academic traditions among and sharing our experience while training opportunities that are professionals, and the educational listening to others’ experiences will currently being developed on level of the general population, make the information diffusion and many professional levels across allows adopting without any learning process easier for us all. in Latin America, and to make drawbacks and complexities the all our professionals aware of development of new drugs both now At this Congress, you will the importance of training and and in the future. co-chair a roundtable constantly upgrading and refining session on “Educational Options in their professional knowledge. The You previously served on the Clinical Research in Latin topics that will be mentioned in this organizing committee for America.” Why is this such an roundtable session will hopefully the fifth offering of this annual important topic and what do you stimulate colleges from different LATIN AMERICA Congress. Why do you continue to hope attendees learn from this contribute to its organization and roundtable session? regions to create and develop presentation? educational and professional courses, As I said before, I think that on both the basic and advanced It is a pleasure and an honor to serve education is a fundamental life levels, in order to expand the as Chair of this upcoming annual support and a central foundation for diffusion of international knowledge Congress, and to be part of such every career in the health and health in these disciplines. ■

VOL 3 ISSUE 5 GLOBAL FORUM 77

GR5-Latin America.indd 77 9/19/11 3:31 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

New Chair for Advisory Council of India

Larisa Nagra Singh

arisa Nagra Singh became encouraging young talent to achieve trial are overshadowed by incomplete Chair of the DIA Advisory their potential and build their career, analysis and publicity of clinical trial L Council of India (ACI) as part and devotes significant time to reports. of the yearly leadership transition building effective networks. Larisa that occurred at our recent DIA 2011 completed her B. Pharmacy from Financial constraints continue to Annual Meeting in Chicago. the S. G. S. Institute of Technology, negatively impact the availability Indore (India) and is a gold medalist; of state-of-the-art infrastructure Ms. Singh has been one of the she did her M. Pharmacy at Panjab – especially in the hinterland, pioneers in conducting ICH-GCP University Chandigarh (India), the alleviation of which would compliant trials in India, and is an specializing in Pharmaceutics. Upon increase penetration and benefit expert in expanding operations for assuming her new role as ACI Chair, a larger population. From the global organizations interested in she shared these thoughts on DIA’s scientific perspective, innovation establishing footprints in India and value to members, volunteers, and and its applications are being the surrounding region. Recently, health care consumers, in India. debated at various public and she was appointed Vice President private forums. Stakeholders are Global Functional Resourcing, Asia What are some of the working on innovation, albeit in Pacific, Quintiles. Prior to this, she current “industry hot topics” silos, and therefore integration of served as General Manager and in India from the scientific their efforts suffer from barriers in Director, in a multifunctional role, perspective? From the regulatory communication and cooperation. with Voisin Consulting Life Sciences perspective? Also, the environment for in Asia Pacific, India, and Australia, academia–industry partnership and where she provided advisory services India is an attractive destination collaboration, which has hitherto to clients interested in placing their and rapidly growing market for been limited, has significant potential trials, or marketing their products, conducting global clinical trials, to be enhanced. in this geographic region. Earlier, which, in turn, is raising concerns Larisa established India offices for about their proper conduct and How does your nation’s ICON Clinical Research and ClinTec oversight. As a result, the regulatory industry, regulatory, and International. authorities have adopted stricter social environments, make the DIA measures to achieve compliance member and volunteer experience In addition to her service with DIA, to global standards and provide in India unique? Larisa also serves as Convener reassurance to the Indian of the Southern Chapter for the population that their interests are India is currently and quickly Indian Society of Clinical Research of paramount importance, and best evolving as a global destination (ISCR), as Leader of the ISCR Ethics practices will be employed during for innovative drug development. Council, and on the clinical research trial conduct. Compensation of Industry in India is gearing up to task force for the Federation of patients participating in trials, and develop the skill sets needed to Indian Chambers of Commerce and registration of ethics committees and support the rapid transformation Industry (FICCI), besides being an CROs operating in the country, is a from a leading drug producer to active votary of the clinical research hot topic of debate. Furthermore, the a leading developer of innovator

INDIA profession. She is passionate about benefits of participating in a clinical drugs. DIA provides a platform

78

GR6-India.indd 78 9/19/11 3:47 PM for our members, volunteers, and May we ask you to please current challenges and thinking in these other constituents, to share the preview some of the topics essential disciplines, chart our paths knowledge and technical know-how planned for discussion at our forward, and provide the audience with that will help this transformation upcoming 6th Annual Conference best practices that they can apply while continue. DIA India can help Indian on Drug Discovery and Clinical they work in Indian settings. pharmaceutical professionals to more Development in Mumbai in actively participate in innovative October? What message would you like drug development activities by to deliver to our DIA providing more frequent and timely The title of our upcoming conference volunteers and members in India? regulatory and scientific input is Global Drug Development & Market from our international network of Access: Converging Strategies & Best The global DIA forum provides a regulatory, scientific, and industry Practices to Benefit Patients. Our platform and environment that assists experts. program committee has diligently different stakeholders from all around worked to bring different stakeholders the world to develop strategies for What specific scientific, together who will deliberate on bringing the best healthcare treatments industry, or regulatory strategies to support innovation. This to mankind. As DIA volunteers and disciplines could DIA help advance year’s conference has eight tracks members, we can play an important the most in India through our interspersed with plenary sessions and role by actively participating in these educational offerings? sessions devoted to special hot topics. forums, and by applying this learning It will present several distinguished in our common endeavor to produce In spite of its growth, India is still at speakers from various regulatory medicines that are affordable, timely, a nascent stage of drug development. agencies, academia, patient advocacy and of the best quality. I urge every There is a need to broaden and groups, and industry. We have invited DIA member and volunteer to reach fortify the knowledge base to come keynote speakers whose views and out and share their ideas to support abreast with other industry-leading remarks will provide opportunities to our initiatives for the benefit of nations and be truly competitive integrate different standpoints, and patients all around the world, and in worldwide. There is tremendous to forge a common vision that patient India in particular. I can be reached on ongoing activity in India in the well-being is the prime focus for every [email protected]. ■ areas of pharmacovigilance, clinical stakeholder. trials, medical devices, biosimilars, vaccines, outsourcing, and more. The key theme of this conference is DIA can bring together scientific, access to affordable drugs using best clinical, and regulatory experts practices. The academia-industry to help formulate suitable focused sessions will identify guidelines and strategies that will current road-blocks and gaps in the make India one of the world’s flow of innovative ideas and their

leading producers of innovative commercialization. The tracks on INDIA drugs. DIA can bring all these outsourcing, pharmacovigilance, different stakeholders together on clinical research, regulatory sciences, a shared platform. and data management will address the Larisa Nagra Singh

VOL 3 ISSUE 5 GLOBAL FORUM 79

GR6-India.indd 79 9/19/11 3:47 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

DIA SELECTS NEW INDIA DIRECTOR Kaushik Desai

“I am excited to be part of DIA which will be playing a lead role in strengthening its base in India by creating an environment for development of professionals and establishment of strong linkages with academic institutions with its innovative educational offerings”.

e are pleased to Industrial Pharmacy Division. IPA Masters in Pharmacy from Mumbai announce the is the major professional society University, and his Diploma in W appointment of Kaushik for pharmacists in India with a Industrial Management from the Desai as Director, DIA India, membership of over 10,000; Kaushik Dahanukar Institute of Management. effective October 1. has been engaged with IPA for many He is based in Mumbai. years as a secretary, editor, treasurer, Kaushik is trained as a Pharmacist, speaker and leader on both a local In October, he will join Kanchan and has over 25 years experience and national basis. During his Patel and Manoj Trivedi who have in key management positions career, he has been actively engaged sustained our operations in India with multinational and domestic with the professional and academic since June. Larisa Singh, Chair, of the firms. Through 2010, he worked communities. ACI, also provided critical leadership as CEO and Director of Global to our operations during the Pharmatech in Bangalore, Kaushik brings to the position transition. In October, Kaushik will where he was responsible for of Director of DIA India, a immediately engage with the Annual operations, business planning and deep knowledge of the global Conference. Soon thereafter, he will development, and meeting global regulatory framework and the travel to Horsham to continue his quality requirements. He currently pharmaceutical environment in on-boarding with the HQ staff. He serves as Vice-President of the India, an appreciation of the work will attend the Global Management Indian Pharmaceutical Association of associations, and a passion for Team and Board meetings in (IPA) and as Chairman of the the mission of DIA. He has his Horsham in November. ■ INDIA

80

GR9-India.indd 80 9/19/11 12:38 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

THE ART OF FACE-TO-FACE NETWORKING IN A DIGITAL AGE

witter, email and Facebook the unexpected benefits that happen 38% through the way the words are are all great social media in the face-to-face space. “In-person spoken and 55% through our facial T tools, but they are poor conversations are organic,” she says, expressions. Phone conversations substitutes for the relationship “and can give rise to spontaneous and emails are simply less effective building power of face-to-face information, opportunities and than face-to-face communication. encounters. Getting ahead in possibilities that would never pop up business requires face time. You need online.” Certainly, when it comes to to increase your social acumen and employment, face-to-face learn effective strategies for in- In her book, Face-to-Face Networking networking plays a dramatic person networking. Those who are in a Social Media World, Mindy role. Statistics from the Right technologically savvy, but shun Selinger underscores the importance Management Manpower Group face-to-face meetings because of a of using face-to-face networking to reveal that 41% of jobs are generated lack of social skills—or those who find what she calls PowerPartners, through networking. Another report opt for electronic communication those professionals in a non- credits 90% of all executive positions under the guise of “efficiency”—are competing, complementary industry to networking. More and more bound to lose out in the long run. with whom we can form bonds and companies recognize the power of build relationships that are mutually face-to-face connections and look to Step Away from Your Keyboard— beneficial. “Look for business hire those with strong networking Your Success Depends on It! relationships, NOT clients, at skills. So, it pays to polish up these “ ‘Schmooze or lose’ is the rule for networking events,” she emphasizes. proficiencies. both personal and professional “These are people with whom success,” says Susan RoAne, keynote you will potentially share ideas, “Don’t just network when you need convention speaker and author of information and resources that will something—network all the time,” Face to Face: How to Reclaim the advance your career.” says Michelle Lederman. In The 11 Personal Touch in a Digital World. Laws of Likability, she advocates And, by schmoozing, she is referring Another advantage to face-to-face face-to-face networking because to that relaxed, friendly, easy-going encounters is that they greatly reduce it builds authentic relationships conversation that connects us with the likelihood of misinterpretation that can sustain and support you others, builds common bonds, and result in deeper connections. throughout your career. establishes rapport and ultimately Face-to-face interaction builds cements relationships. stronger ties than Skype, phone or Where are the Best Networking

emails. Opportunities? CAREER TIPS According to RoAne, when we In a word, the answer is “everywhere.” use technology to avoid human UCLA Professor Emeritus, Albert Networking opportunities are interaction, we may save time, but we Mehrabian, supports this in his all around us, both inside and lose out on the opportunity to build findings about the communication outside your company: from formal the bonds of trust that strengthen of feelings and attitude: only 7% is networking events and chamber our connections, and we miss out on communicated through our words, meetings to social events, like

81

CT1-Networking.indd 81 9/20/11 2:34 PM charity fundraisers and weddings, “You want quality not quantity,” Get the Most out of Networking as well as in casual encounters at advises Carey McBeth, etiquette Remember, you’re not selling! the supermarket, on the ball field, at consultant. “If your goal is to gain Your goal is to build long-term, your gym, in a waiting room or on credibility and visibility, offer to be a mutually beneficial relationships. an airplane. Strike up conversations speaker at a conference, association Following are some suggestions from whenever you can—you never know or alumni event. You’ll be surprised networking experts: where they might lead. at how many people come up to you afterwards to talk one-on-one and Be intentional. Know why you are Begin targeting your networking ask for your business card.” Consider there. “A lot of the work happens efforts based on your goals, advises joining a Toastmasters club to gain before you step into the room,” says Anne Baber, coauthor of Make Your the skills and confidence for speaking DeNucci. “Have a plan laid out in your mind in advance. Ask yourself Contacts Count. Do you want to gain one-on-one and in front of an beforehand: why are we getting new customers, become more visible audience. together or why am I attending this in a particular industry, or advance to event, what do I want to get out of it, a new position? Depending on your Volunteering is another great way to get to know people on a personal whom do I want to meet, what will answer, you might profit most from make this worthwhile for me?” joining a professional association, level and build trust. As others offering to speak on a guest panel involved in the project get to know you, they are more likely to conduct Bring an optimistic outlook. Go or contributing to a trade magazine. to have a good time and to learn, But, don’t dilute your efforts by business with you or forward business to you from within their reconnect and meet people. “If you joining more groups than those for have a positive attitude, the room will circle of influence. which you have time. work you,” says RoAne. Find “your people” says Patti Baber enforces the Rule of Six. Be prepared to share. Read DeNucci, author of The Intentional She recommends being involved newspapers, business publications, Networker. The 80/20 rule posits in six different networking arenas. blogs, books and articles. Come that 80% of your success is created They can be industry associations, to a networking event or lunch by 20% of your contacts. “You’ll the organizations that your best with stories to share, timely news want to figure out why they are customers or clients belong to, or to contribute, and ideas that make your top 20%, where you met leisure time groups. The Rule of Six you interesting and memorable. them, the kind of people they also means that you need six separate “Otherwise, you may end up in your are and what circumstances built default selling mode,” warns Selinger, encounters with your critical those relationships.” Jot down contacts before you can prove your “and if you treat people as prospects this information, track it and try they will run the other way.” trustworthiness and competency. So to reproduce it. Find where ‘your don’t just be a member—be an active people’ are and be where they are.” Be an early bird. Selinger arrives member! It may be in an informal setting; early to check out the sea of name it may be at your local watering tags at the registration desk. “I look We all have four immediate hole, philanthropic event, or leisure for the names of people I’ve been networks according to Baber: our activity. trying to talk to or companies I’d LifeNet (family, friends, leisure time like to connect with, and I stand just contacts), ProNet (professional Also, while you’re experimenting inside the entrance to greet people as contacts outside of work), WorkNet with different networking venues, she they arrive.” (those we work with daily), and suggests recording your impressions. OrgNet (people in our organization Mark down right on your calendar Let them know who you are at with whom we have deliberately next to the event a (+) for fantastic, a glance. Selinger also advises cultivated relationships). So, to find (0) for okay or (–) for a waste of time. investing in a custom nametag to six different networking arenas, You’ll soon discover which events use whenever possible. “Leave off all we need to do is look around. and organizations offer you the best distracting logos; all people want to Reading a local business publication networking opportunities—and know is: what industry you are in and

CAREER TIPS or a quick Web search can help, too. which you should drop. who you are. Your company name

82 GLOBAL FORUM OCTOBER 2011

CT1-Networking.indd 82 9/20/11 2:34 PM should be large enough to be visible saying: “I’ve enjoyed meeting you; that allows you to choose a greeting from ten feet away and your nametag I know you have other people you card, customize your message and should be worn high on your right would like to meet and I do as well.” even include a gift card. All is sent lapel, above your handshake.” Or, “I don’t want to monopolize out via first-class mail; suddenly, you...” You could also simply personalized follow up becomes easy Divide and conquer. Don’t sit with introduce the person to someone and routine. the people you came with; colleagues else and move along. If there’s should all go in different directions. PowerPartner potential, says Selinger, More Networking DOs to Consider Later, you can introduce each other then end the conversation with: “May Have patience. If you connect to the people you’ve met, suggests I have your card? ... Let’s get together with someone who responds to an Baber. and see if we can help each other invitation with: “I’m busy for the develop some business.” Or, “May next few months” or “This isn’t really Start with small talk. Begin each I give you a call tomorrow? I have a good time for me,” don’t take this conversation with a comment related some ideas.” as a rejection. People have busy to the event. Get comfortable by schedules, says DeNucci. Send them making introductory remarks and Don’t hand your business card out a handwritten note and let them asking questions. like a flyer. Give your card only if know that you’d like to get together you have been asked for it or if there when time permits and let them Be a focused listener. Shut off is good reason to hand it to someone, know what you would like to talk your cell phone and don’t answer says McBeth. about. “Keep the connection going any calls or glance down at any and show your willingness to wait; text messages. Make eye contact, Follow up! In real estate it’s about sometimes these turn out to be our nod, smile, laugh and offer your full location, location, location. In best connections.” attention. Answer a question with a relationship building it’s about follow comment and return a question so up, follow up, follow up. RoAne’s Remember networking IS for that the conversation volleys back number one rule of networking is: everyone. It’s not only for those in and forth. “Make it about them,” says Do what you say you will do, when sales. The fact is you offer more value DeNucci. “Remember, it’s better to you say you will do it. DeNucci to your company when you have a be interested than to be interesting— concurs, “Promises made should be large bank of resources to call upon. and to be impressed rather than to promises kept.” “For instance,” Selinger explains, be impressive. It’s not about you; it’s “you will know whom to call when about making the people around you Adam Small, founder and CEO of you need: a source for a project, an feel comfortable.” Strategic Business Network, equates outside opinion or an introduction.” building a business relationship with Give first and give freely. But, don’t dating. “A first conversation is like Connect at all levels. Don’t just give with the intention of getting a first date. You don’t go on a first network with higher ups. “The best something in return. Baber sits down date and then get married.” If you leaders are those who generate each morning and asks herself: What just throw a person’s business card people who want to follow them,” am I willing to give away today? “I in a drawer and don’t follow up with says Lederman. “Every relationship collect things to give away—things the next step, then you don’t have a counts. Find a person you connect of interest and worth: articles, web relationship. with and build that relationship— links, and personal contacts that are whether it’s the receptionist or the of value to others.” When you give “When it comes to follow up, find mail room clerk—but do it because it a person something, naturally they a balance between your strength feels real. Always be authentic.” want to give back. Smart networkers (writing or calling) and what’s best

are also great matchmakers; they for the person you’re trying to Think outside the box. McBeth CAREER TIPS make introductions and help others reach—and switch it up until you believes in using creative ways make beneficial connections. find what works,” he suggests. to connect: walk a pet--they’re great conversation starters, drop Have an exit strategy. When you Small uses a convenient and a football off at a physician’s office realize that there is little relationship innovative way to stay in touch: www. with an invitation to a weekend potential, make a graceful exit by sendoutcards.com, an online service game, deliver a potted Gerber daisy

VOL 3 ISSUE 5 GLOBAL FORUM 83

CT1-Networking.indd 83 9/20/11 2:34 PM to the receptionist on the first day new people at corporate training For instance, McBeth interacts of spring. Be imaginative, fun and sessions, on the company softball with the people in her networks by memorable. Listen to what others tell team or while working on a special sending out hints and tips, posing you. If the administrative assistant task force,” says Baber. “Today, we questions to them and posting polls. mentions her son is graduating, send tend to quarantine workers into a congratulatory note. Gatekeepers silos and lose that collaboration. By We can’t always pick up the phone often feel invisible; thoughtful networking with those outside your and we can’t always run out to gestures go a long way in building immediate work group, you can get face-to-face meetings, but we can their trust. fresh ideas and often solutions that stay close with our established will help work flow better in your connections via a quick little See shyness as an asset. It varies by own department.” what source you read, but generally “congratulatory” response when speaking, more than half of us have Can Social Networking Still Play we learn of their promotion, award shyness issues. In other words, we a Role? receipt or other good news via feel uncomfortable or out of place in Absolutely! It’s a great tool for both LinkedIn Updates. “Social media unfamiliar situations. While shyness follow up and reconnaissance. gives you a reason to connect can hold us back, ironically, it can “Online networking is great for without being too obtrusive,” says also give us an advantage. For one, finding people and allows me to Lederman. introverts are excellent listeners, broaden my reach and develop know how to ask questions and rudimentary relations,” says Baber. RoAne uses a “surf and turf” connect on a deeper level, points out approach to finding and maintaining Lederman. “I like to mine my existing database her critical connections. She surfs for hidden PowerPartners,” says the web to research individuals and Secondly, they have the ability to Selinger. “Then, I explore social relate to others who are shy. Instead their companies in order to prepare media sites like LinkedIn and of focusing on your own discomfort for face-to-face meetings and uses at events, think of how you can make Facebook to find out more about social media to reconnect with older others feel more at ease. Act as the the person and see what we have in contacts. However, she emphasizes “host” and invite others into the common—so I can begin building that the real connections happen conversation; in the process, you will a bond.” She also posts testimonials not in cyberspace but in face-to-face on LinkedIn and uses blogs and create a more relaxed situation for space (turf). yourself and others, says RoAne. other online forums to “good mouth” people. It’s important to master the skills of Network internally. By cultivating face-to-face networking in order to DeNucci thinks LinkedIn, Facebook relationships with people throughout build authentic, mutually beneficial your organization, you gain access to and Twitter are great ways to stay in relationships—but, continue to use new information. It puts you in the touch and fantastic complements to social networking in between to grapevine and lets you learn of new networking because, even with the opportunities for personal growth best intentions, it may be difficult increase familiarity and stay top of and advancement within your to connect face-to-face as often as mind. If you do all this, you are sure company. It gives you mentors and we wish. Social media allows us to gain invaluable resources and sounding boards outside of your own to continuously engage with our contacts that will help you achieve group. “Take advantage of meeting contacts. your career goals. ■

TAKE THIS NEWTWORKING QUIZ! Those interested in measuring their present skill at building relationships and learning what aspects of their networking acumen could use improvement, can visit www.contactscount.com and take a 40-item, online Networking Competency Assessment©. CAREER TIPS

84 GLOBAL FORUM OCTOBER 2011

CT1-Networking.indd 84 9/20/11 2:34 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

DIA 2011 Session Report: Pricing & Reimbursement

uccessful commercialization These markets have only so many of medicines in the emerging Session Chair: resources to spend on health care, S markets of Latin America Alberto Grignolo, PhD he continued, and they must know and AsiAsia depends on their inclusion PAREXEL Consulting they are receiving value for these in local reimbursement schemes at resources. In response, companies a good price. The DIA 2011 Annual Speakers: developing drugs for these markets Meeting session on Pharmaceutical John Brennick, MPA must ask and understand the answers Pricing & Reimbursement Policies Janssen Global Services, LLC to new types of questions: What type & Practices in Asia Pacific & of evidence are payers looking for? Latin America: Impact on Drug Raj Long, MA, MSc Are there specific outcome endpoints Development & Registration Strategy Novartis Pharma AG, they prefer in certain disease areas? (#226) first reviewed pharmaceutical Switzerland How can we generate this evidence in pricing and reimbursement our clinical development programs, (P&R) policy trends within these Alexandre Schiola, MD and report it in our registration trial critical emerging markets, and Bayer De Mexico, S.A. De C.V., data? These answers must change how then suggested a new model that Mexico regulatory, clinical, and commercial more fully integrates these P&R groups collaborate during drug considerations early (“upstream”) in convergence or else there will be development and registration, and drug development programs, and difficult days ahead.” how innovators/sponsors, regulators, thereby facilitates access to these and payers interact thereafter – two markets. Regulatory approval no longer means more emerging convergences, Alberto automatic market access. Specific noted. “I want to use the phrase ‘Drug safety, efficacy, pharmacoeconomic Development with Reimbursement (such as comparison to the cost of John Brennick delivered A Primer in Mind, ’ ” said Session Chair treatment with a local comparator), on Worldwide Market Access / Alberto Grignolo in his introductory and other data, are required for Reimbursement, describing the new remarks. Alberto presented data formulary/pricing listings in and increasingly powerful voice that illustrating how growth in these most Latin American nations. As has emerged from the overlapping,

“Pharmerging Markets” (as IMS managing health care resources harmonized interests of clinicians PROGRAM NOTES calls them) will largely drive the continues to grow more complex and (“How well does it work?”), regulators global pharmaceutical market by cost-conscious, health technology (“Does it work, and safely enough?”), 2014, using the DIA 2011 theme of assessment (HTA) organizations and payers (“Is the price worth it?”). convergence as perspective: “These in such countries as Argentina, Who are these payers, and what do are the markets that are going Brazil, Chile, Columbia, Mexico, and they want or need to make these to determine the growth of the Uruguay, have gained importance. decisions? In many countries, they’re pharmaceutical industry,” he said. “While these markets have potential considered the stewards for the health “Industry and other constituents for growth, they also have a lot of cost care of their constituencies, plus they need to pay attention to this containment,” Alberto explained. have other customers (such as

85 85

PN2-Pricing and Reimbursement.indd 85 9/20/11 5:50 PM members, stockholders, politicians, reliable water supply, 125 million of phase 3. But by integrating price governments, etc.) beyond these have no regular access to health considerations earlier, in tandem with constituencies. During pricing care, and 146 million lack basic dosing and comparator decisions negotiations, they want evidence that sanitary services. Nearly 25% of at the end of proof of concept or a product will deliver clinical value this population lives on less than at the beginning of phase 2, you – robust, believable evidence that it $2US a day and yet most health care create a new model that more clearly will prevent more expensive hospital expenditures – up to 80% in Mexico generates clinical evidence of the true stays or employee absenteeism, or will and Brazil – are out of pocket. Even value of the therapy, a model that Raj offset other health care costs. in Brazil, Latin America’s richest called “value proposition integrated nation, there remains a tremendous clinical development.” Next, John overviewed the asymmetry in access to health care for referencing and other P&R systems patients with private health insurance She offered some specific suggestions used by several different payers in and for those without. Throughout on how to build this new model: Europe, Latin America, and Asia. the region, health care needs are Seek out and consolidate the needs Many Latin American countries increasing, but few nations have the of patients, payers, and regulators, base their pricing on Brazil, which resources to spend more on health. specifically for your proposed therapy, identifies the lowest price in ten in development plans. Consider your reference countries and establishes Raj Long concluded the session by target market’s social and political that as maximum price for the exploring these P&R policies’ Impact environments, and local medical product patent life. Asia contains on Drug Development & Registration standards and (comparator) therapies. a wide range of reimbursement Strategy. She introduced the concept Understand the payer’s post- systems: In Taiwan, for example, new of “pricing vs. affordability” into these development needs, and simulate drugs supported by trials conducted market access discussions: At the them in your development. in Taiwan can receive as much as a bottom line, “access” really means “at 10% markup to reward research on an affordable price.” In our current, cost-constrained ethnic-specific efficacy and safety. environment, Raj concluded, you Raj proceeded to illustrate how don’t need to spend additional Alexandre Schiola presented incorporating pricing considerations resources on P&R decisions. But health care indicators, economics, in early drug development phases can WHEN you consider P&R in your systems, and case studies, as he lead to more efficient downstream drug development programs can overviewed Pharmaceutical Pricing generation of the specific efficacy be just as important as HOW & Reimbursement in Latin America. and comparative evidence that you consider it. In our current Clinical research professionals often payers look for in determining circumstances, P&R decisions cite the attraction of Latin America’s reimbursement. At present, most can no longer be just the work of enormous patient population, but drug development programs typically your commercialization or pricing it is not without its challenges: begin to consider pricing data around department, but must be the Out of approximately 569 million the time that safety and efficacy collective responsibility of your entire inhabitants, 61 million have no profiles are developed near the end development team. ■

Learn more about regulations and commercialization in emerging markets through DIA’s new online training series:

The Regulatory Landscape and Key Considerations for Product Development in Emerging Regions Online Training Series Begins October 26

Invest to Win in Emerging Markets: The Value of Integrated Regulatory and Commercial Intelligence Online Training Offering on November 16

Register for both of these online training opportunities and receive $100 off your registration.

For more information, or to register, visit the DIA website at www.diahome.org, select Training, Find an

PROGRAM NOTES Educational Offering, and search event ID 11472 and 11473

86 GLOBAL FORUM OCTOBER 2011

PN2-Pricing and Reimbursement.indd 86 9/20/11 5:50 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM Freda Lewis-Hall, M.D. Healthcare Businesswomen’s Association Woman of the Year Reflects on DIA 2011

reda Lewis-Hall, M.D., to the social responsibilities of health monitored and managed. Her term Chief Medical Officer and care leadership – especially in making on the PCORI Board of Directors F Executive Vice President, sure that people have the education lasts until 2014. Pfizer,Pfi er IInc, contributed to two panels and understanding to make the at the recent DIA 2011 47th Annual best health care decisions.” As HBA Global Forum recently had the Meeting, held in Chicago. Woman of the Year, Dr. Lewis-Hall privelege to talk to Dr. Lewis-Hall was profiled in the April 2011 issue of about her experiences at DIA On Monday, June 20, she served as Pharmaceutical Executive. 2011. Some excerpts from that a panelist during the session titled conversation are below. Comparative Effectiveness Research & Among her other professional Health Technology Assessment: How accomplishments and contributions, National Agencies are Addressing Dr. Lewis-Hall has served as a special the Challenge, which was chaired advisor on patient outreach and by Joshua S. Benner, DrSc, PharmD, education for minority Americans Research Director and Fellow, to the National Institutes of Mental Engleberg Center for Health Care Health. She serves on the boards of Reform, The Brookings Institution. The Institute of Medicine’s Forum This panel discussed the work of on Drug Discovery, Development, U.S. government-funded agencies in and Translation; The Foundation for the implementation of comparative the National Institutes of Health; effectiveness research (CER), as well The Harvard Medical School Board as other nations’ health technology of Fellows; the Society for Women’s assessment (HTA) policies and the Health Research; and the American What did your perspectives potential impact of CER and HTA Heart Association’s “Power to End as a physician caregiver and on the development and life-cycle Stroke” initiative. She is a Fellow of industry executive contribute to management of biopharmaceuticals the New York Academy of Medicine the panel discussion on compara- and medical devices in the US. and a Distinguished Fellow of the tive effectiveness research (CER) The following day, Dr. Lewis-Hall American Psychiatric Association. and health technology assessment participated in Paying for 21st Century (HTA), and to the Executive Innovations, an Executive Session In September 2010, Dr. Lewis- Session on Paying for 21st Century panel discussion chaired by Kenneth Hall was appointed to the Board Innovations? I. Kaitin, PhD, Director, Center for of Governors for the new Patient- the Study of Drug Development Centered Outcomes Research and Professor of Medicine, Tufts Institute (PCORI). Established by the First of all, let me say that

University School of Medicine. Patient Protection & Affordable Care your order is exactly right: I PROGRAM NOTES Act of 2010, PCORI is a nonprofit consider myself to be a physician In January, the Healthcare organization that assists patients, caregiver above all, and I stress in my Businesswomen’s Association named clinicians, purchasers and policy- role as an industry executive that the Freda Lewis-Hall 2011 Woman of the makers in making informed health interests of patients trump all others. Year. “Dr. Lewis-Hall sets the tone decisions by executing research It’s always a delight for me to bring for all of us with her unique abilities projects that provide high-quality, together these two perspectives and as a talented physician and leader,” relevant evidence on how diseases, to emphasize that this is the order in said HBA President Deborah Coogan disorders and other health conditions which I go about my daily work. I did Seltzer in announcing this award. can appropriately and effectively try to leverage both of those per- “She has a longstanding commitment be prevented, diagnosed, treated, spectives in the panel discussion – to 87

PN1-LewisHall.indd 87 9/19/11 5:03 PM stress that, in my career, whether it blinding trachoma in Africa?” The opportunity to go to the people who was in frontline patient care or answer is: “No, it’s not.” But it’s will be directly impacted by the through my current role as Pfizer’s absolutely the right thing to do, so outcomes of this research and ask Chief Medical Officer, I’ve seen CER that’s what we do. We can provide them what is important for them to and HTA from nearly every vantage example after example, both from the know and understand about diseases point. My comments added in my company I work at as well as from and treatments. experience not only as a physician industry as a whole. We make caregiver, but also as a patient myself decisions to move forward when the Expanding the definition of “stake- and as a caregiver for loved ones. I course of action may not be the best holder” beyond lip service to try to add that perspective as well. way forward from a financial point of patients and patient advocates, to view but is absolutely the right the inclusion of such individu- As a doctor, I’m always seeking well- human thing to do. Our focus is on als and groups as equal partners, researched evidence to guide the patients and the people that we serve. is a thrilling opportunity. choices that patients have to consid- That is what drives our decisions. I er, and that I, as their physician, need firmly believe that by putting patients As for DIA, the DIA Patient Ad- to be able to share to help them make first, success for all stakeholders, vocate Fellowship Program is just good choices. As a researcher, I have including our investors, will follow. one example of programs that to tell you that I’ve been consistently provide an opportunity for medi- stunned by the lack of evidence that During the executive session on af- cal industry leaders to meet with is available to both doctors and their fording – more to the point, who’s patient advocates to discuss how patients. The work that I’ve done going to pay for – innovation, I policy may affect drug discovery over the years has often focused on delivered an unpopular answer that and approval, as well as patient ac- what I’ll refer to as “special popula- sounded something like this: Science cess to new treatments. These kinds tions” – women, children, racial and has been asked to deliver landscape- of dialogs are critical to ensuring ethnic minorities, the elderly – and shifting innovations to improve we’re defining quality and value I’ve grown to recognize that if there’s health care. You can’t ask us to do from the patient perspective. a problem with a lack of data from that and, at the same time, use the an overall comparative standpoint, same old, archaic system for how it is an even bigger problem when people are going to access health Is there a message you’d like you get to the considerations for care. That can’t happen. We need to to deliver to DIA’s constitu- patients in these special groups. put the same innovation and creative ents on these subjects? thought that we’re putting into the Lastly, I work as an industry execu- science to advance health into the tive for a company that’s rooted in system to advance health care – and I believe that research – sci- science and innovation. So I look at this system includes how people ence – is really hitting its comparative effectiveness, in par- are going to access these therapies. stride, and that we’re going to be able ticular, to support the value propo- to answer some of the most vexing sition: How do we ensure the safe questions left surrounding disease in and effective and appropriate use From your perspective as a relatively short order. We’re picking of medicines? How do we get the physician, how can PCORI up the pace and we’ll be able to right medicine to the right patient at – and DIA – impact the quality deliver new therapies. I want us – col- the right time for the right reasons, and cost of health care for patients lectively as a health care industry, as and ensure that it’s used properly in the US? parties interested in health care – to when it gets there? That’s really the think as creatively as possible on what work that we do, beginning to end. the needs really are, and how we can With the Patient-Centered use everything available to us to Outcomes Research Institute answer these questions, and then How do you, as an industry we have a unique opportunity to ask, provide access to care to the people executive, manage the “What is ‘patient-centered’ really all who need it. What I want to under- balance between the financial and about?” Our work in this public- score is that we need innovation humanitarian aspects of that value private partnership is guided specifi- beyond the lab. We need innovation proposition? cally by patients, providers and other everywhere. Innovation should stakeholders. We’re expecting them encompass not just the “what” of to help us understand the important health care but the “whom,” the “how,” Industry executives find questions to be asked by this area of the “where” and the “when.” Every ourselves asking that same research and to help us answer them. dimension of health care—from how question all the time. There are issues This isn’t the bright scientist sitting we do it to how we finance it—should

PROGRAM NOTES like, “Is it profitable to make major around and thinking up the right be the focus of our creativity and the donations of medicines to get rid of research questions. This is an beneficiary of our great ideas. ■ 88 GLOBAL FORUM OCTOBER 2011

PN1-LewisHall.indd 88 9/19/11 5:03 PM DIA 2011 Presentations Online Until December 23

No matter where you live or work, full conference registrants can freely return to the educational content delivered at our recent DIA 2011 Annual Meeting in Chicago: All available DIA 2011 audio-synchronized PowerPoint presentations have been posted and will remain accessible online at no cost until December 23. One-day registrants will have access to all available presentations for the day you attended.

Even if you were unable to join us in Chicago, you can still purchase the complete conference set of available presentations for just $699, or one or more of our 18 meeting tracks for just $199 each. In addition, group discounts for full conference sets are available. Please contact [email protected] for more information.

To access or purchase these presentations, click on the DIA 2011 icon on our www.diahome.org home- page, or visit www.diahome.org/dia2011. You will need to enter your DIA User ID and password to verify your Annual Meeting registration status. If you’ve forgotten these login credentials, please use our DIA login reminder at https://www.diahome.org/DIAHome/Common/Templates/LoginReminder.aspx.

Please note: Continuing education credit is not available for archived presentations.

AN6-Presentations.indd 1 9/19/11 5:11 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 YOUR TOPIC, TIME & PLACE DIA IN-COMPANY TRAINING

hy expend your budget constraints, and increased is perennially strong interest in company’s budget on demands on employee time, in- our Clinical Statistics for Non- W expensive travel costs, company training allows you to Statisticians, Introduction to Good or on employee time out of the office, provide professional development Clinical Practices and Auditing, and when you can bring industry experts opportunities for your employees Regulatory Affairs courses, year after to your facility? As a leading provider in a more cost-effective manner. year.” of professional education and Additionally, because many courses training solutions, DIA offers a can be tailored, you can focus robust in-company training program on specific areas of need within DIA can also work with you to that provides a more cost-effective your organization. You may select outline the professional development way to train large numbers of content from multiple instructor- pathway for your staff, and create employees. DIA’s in-company led courses to create your own a curriculum and/or series of training program consists of the unique training experience for your educational opportunities that same quality instructor-led courses team, and the instructor will come foster continued growth within your we offer nationally; however, you can to your organization to teach your team and ultimately improve your also tailor these courses to meet the employees. This minimizes stress company’s performance. specific needs of your organization. on your organizational staff because they can remain connected with DIA understands each business colleagues during breaks; it also Although DIA’s in-company portfolio comes with its own unique eliminates the need for travel and focuses on the instructor coming to challenges, competitive situations, prolonged time out of the office and your organization, DIA also provides and corporate culture. But you can away from family. online learning opportunities align your training needs with your that can be tailored to meet the business goals and objectives by DIA offers four curricula in multiple educational and schedule demands working with DIA to jointly design disciplines: Clinical Research, of your employees. To learn how Clinical Safety & Pharmacovigilance, an in-company training experience DIA can help build your team and that meets your training goals Project Management, and Regulatory improve your company’s overall and fits within your budget and Affairs. “Our most popular In- timeframe. Company training courses vary performance, please contact Jessica from year to year,” explains DIA Kusma by telephone at 215-442-6182 Against an industry backdrop of In-Company Training Manager (US) or by email at Jessica.kusma@ turmoil in the global economy, Jessica Kusma. “Even so, there diahome.org. ■

Here’s what past participants say about DIA’s In-Company Training Program: Mention this ad “The instructor’s enthusiasm and knowledge made three full days and receive 10% go by smoothly, quickly, and effectively.” off your 2012 in- “This was the best GCP course I’ve ever taken. I wish the instructor could have stayed longer!” company offering if “The instructor’s knowledge of the subject matter was superior. We enjoyed having him and look forward to future in- scheduled by company training courses with him.” December 31, 2011.

ASSOCIATION NEWS ASSOCIATION “This was the first statistics course where I actually understood something – very effective!”

90

AN1-InCompanyTraining.indd 90 9/19/11 5:17 PM PRINT CSO DIRECTORY COMING FOR 2011 nen of the clinical research industry’s most the annual hard copy directory, which is then respectedr reference guides, the DIA delivered to all professionals with a full DIA O ContractC Services Organization (CSO) membership and others who work across every facet Directory compilesc company descriptions and contact of the discovery, development, and lifecycle information from hundreds of companies that provide management of pharmaceuticals, medical devices, and services for every phase of the clinical trial and drug related products. development process. Published online and in print, our annual directory delivers information about Don’t miss this opportunity to guarantee that your your services to industry professionals who use these company’s services are seen by our international, services every day. multidisciplinary DIA membership and other industry professionals around the world. Additional advertising Your company listing, consisting of your company opportunities are also available in the print edition. To name and contact information, narrative company learn more about these opportunities or to purchase description, and services you offer, hyperlinked to your your listing, please contact Michael Boucher, Influence Web site and e-mail contact address, appears in our Media LLC, at mboucher@influencem.com, or select online directory for one full year. In November, these “Publications: CSO Directory” from the left navigation online listings will be downloaded and printed into bar of our www.diahome.org website. ■

7/2+).'4/'%4(%24/ !$6!.#%0(!2-!#/6)'),!.#%

At Drug Safety Alliance, we focus on helping pharmaceutical, biotech, medical device and consumer health organizations mitigate risks while ensuring patient safety and product longevity. It’s a collaborative approach under a shared mission, providing peace of mind in a rapidly evolving industry.

www.drugsafetyalliance.com

AN4-CSO Directory.indd 1 9/20/11 1:05 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

FDAFDA PROCESSPROCESS DEMYSTIFIEDDEMYSTIFIED BYBY DIADIA COURSECOURSE OFFERINGSOFFERINGS

remors are felt in the halls not true, he says, and there is a team is the day they face an FDA of pharmaceutical lot of needless expense and worry Advisory Committee. T companies all around the expended by those in the field The challenge is daunting: Present country when an FDA drug of drug development because a convincing argument for approval application has been filed. Whether they either “don't follow or don’t in an hour, then answer questions for a new drug or the new use of an understand what the FDA wants.” from a panel of experts whose vote existing drug, the anxiety is still the The FDA protocol is very clear and could spell the success or failure of same. Will it be successful? Did we provided in a comprehensive, readily a product — even a company,” Taft miss something? Anything? Will we available regulation handbook writes. It is only after this intense, get a letter? Or worse, a phone call which is updated regularly with real-time hearing is over, can a from an FDA official demanding “guidances” that are non-binding collective sigh of relief be uttered. additional information? for the FDA but provide current How do you prepare for such a thinking in a particular research high-stakes event as a FDA Advisory Pharmaceutical companies, drug field. “Use guidances when preparing Council hearing or AdComm as it researchers and clinicians alike are an application because they is known in the industry? DIA will stymied by the beast known as the provide direction on situations that offer its first course on the topic FDA. For many involved in drug regulations did not anticipate but later this fall where the development production, the FDA remains an always comply with the regulations of AdComms and their current enigma and the review process can in your submission” in order to have processes will be discussed. Most paralyze even the most sophisticated the best shot at getting your drug importantly, instructor Taft will among them. Not necessary, says approved, D’Addamio recommends. George H. D’Addamio, PhD, who examine the best preparation specializes in the preparation of Even after a drug has successfully tactics a company can take: How clinical development documents navigated the arduous review do you craft an argument for and demystifies the FDA submission process, the final step before bringing approval (critical to the panel’s and review process in the DIA the drug to market can be just as understanding)? How do you prepare training course, Overview of Drug grueling. New FDAAA guidelines for the bevy of questions from the Development. require all drugs to undergo an FDA panel? How do you motivate your Advisory Council hearing and, as is team, stay on message and gain "One of the greatest misconceptions discussed in another article in this approval? All that, plus a breakdown about the FDA,” says D’Addamio, issue by Peter Taft, pharmaceutical of FDA lingo and how to understand “is that it is unreasonable and that companies still fear that part of the it and use it in your presentation. Go every time a product fails, either FDA approval process tremendously. to www.diahome.org for information in the review phase or at market, “One of the most stressful moments on these and other learning ■ REGULATORY UPDATES REGULATORY it is the FDA’s fault.” This is simply in the life of any drug or biologic opportunities.

92

RU2-Demystifying.indd 92 9/20/11 2:37 PM Q&A Dr. George D’Addamio, PhD President, PharmConsult, Inc.

What is the greatest misconception day, twice daily, etc.). These are the their physician thereby determining about the FDA? That it is conditions under which the drug is their contra-indications or risk factors “unreasonable.” Clinical trial studied during the clinical trial and for taking the drug accurately. applications have very specific the arena in which adverse events and inclusion and exclusion criteria serious adverse events are measured. Why do US drugs take so long to designed to keep homogeneity Once the drug is approved by the reach the market? There are not and excessive risk out of the study. FDA and distributed on the open enough patients to take a really deep There are a well-defined group of market, there is no control over look at rare events that occur from regulations that researchers simply how and/or why the medication is drug usage (i.e, a study may have need to follow in order to submit a dispensed by physicians to particular 10,000 participants for a medication successful FDA new or new use drug patients. Often times, the physicans that eventually could be used by application. are not prescribing as was done so millions). Our process builds in extra in the clinical trials, the patients are time for a broader scope time-wise Everytime a product fails, it is then not using the drug as studied for measuring adverse events in the perceived to be the FDA’s fault? and the results, therefore, are not context of use. Pharmacovigilance Why? Once a product is approved as intended. In addition, there is allows the medical researchers to by the FDA it is done so for a certain no way of determining if the patient evaluate the post-marketing effects of patient type with a specific disorder/ is complying with the physician’s approved drugs and is very important illness, at a specific dosage, for a prescribing guidelines or has because of this. specific timeframe of use (one a provided accurate medical history to

DID YOU KNOW?

UÊIn 2007, the biopharmaceutical UÊCost of new product development industry spent 80 billion USD in is estimated to be 1.2 billion USD research and development UÊFor every 10,000 compounds UÊApproximately 18% of domestic screened, 250 will advance to pre- sales are reinvested in R&D clinical trials, 5 will go on to clinical trials and ONE will be approved. UÊOutpatient prescription drugs But, each compound will cost in accounted for only 10% of national the billions to develop, whether it health care expenditures in 2006 advances or not UÊDespite this data, only 44% of UÊThe review time specified in FDA consumers have a favorable regulations for IND is 30 days REGULATORY UPDATES opinion of the pharmaceutical industry UÊThe review time specified in FDA regulations for NDA is 180 days UÊDrug development can take 10-15 years and patent life is 20 years UÊThe Bureau of Chemistry, the precursor to the FDA was founded in 1862 during the presidency of Abraham Lincoln

VOL 3 ISSUE 5 GLOBAL FORUM 93

RU2-Demystifying.indd 93 9/20/11 2:37 PM FDA: TIMELINE OF GROWTH

1862 Bureau of Chemistry formed under Abraham Lincoln, President

1906 Pure Food and Drugs Act founded as a result of Dr. Wiley’s Poison Squad

1938 Federal Food, Drug and Cosmetics Act was the first act to require drugs to be test for safety

1962 Kefauver-Harris Amendments formed the basis for the current IND drugs and required demonstration of efficacy and safety. First time formal FDA approvals were mandatory

1987 IND Rewrite Regulations ensured data integrity and protection of human participants via informed consent

1988 Expedited NDA Approval Process for Life-threatening illnesses was precipitated by the AIDS epidemic and starts reliance on post-marketing surveillance to assess safety

1992 Prescription Drug Use Fee Act (PDUFA) started fee collections for FDA applications to fund hiring of more NDA reviewers 1997 FDA Modernization Act (FDAMA) extended PDUFA and fast tracked drug approval, and expanded patient information access

2007 FDA Amendment Act of 2007 (FDAAA) required post-marketing studies and clinical trials with specific reporting requirements REGULATORY UPDATES REGULATORY

94 GLOBAL FORUM OCTOBER 2011

RU2-Demystifying.indd 94 9/20/11 2:37 PM OCTOBER 2011, VOL 3 ISSUE 5 GLOBAL FORUM

ŻIN MEMORIAM Ż PAUL MEIER Randomized Clinical Trial Pioneer

n August, Paul Meier, a a study and the best way together US statistician was the one who statisticians who has been convincing evidence of a treatment’s influenced US drug regulatory I creditedc with revolutionizing effects.” agencies and, hence, clinical the randomized ra clinical drug trial researchers throughout the US and protocol still in effect today, died Meier’s protocol differed from other countries, to insist on the at 87 in his Manhattan home from previous trials in that the drugs central importance of randomized complications of a stroke. Prior to received by patient participants evidence.” Peto praised Meier saying Dr. Meier’s advocacy of randomized under his system were randomly that, “That strategic decision half controlled clinical studies, drug assigned, so one group received the clinical trials results reflected a level standard treatment while the other a century ago has already saved of bias that unintentionally occurred group received the experimental millions of lives and those millions during research based on the treatment. This removed the choice should be attributed to Paul.” imprecision with which patient pools of who received which treatment were chosen. from the hands of the researchers, Another major contribution to and rendered both the trial groups medical statistics made by Meier, In the New York Times’ obituary identical in all ways except for the in association with Dr. Edward L. following Dr. Meier’s death, reporter drug they received. Today, the NIH Kaplan, is a formula used to estimate Dennis Hevesi explained that “Before has allocated a large portion of their patient survival rates. The method, randomization, the science of clinical budget to randomized drug trials called the Kaplan-Meier Estimator, trials was imprecise. Researchers, for and the FDA requires that all new originated in 1958 and has become example, would give a new treatment drugs undergo a randomized trial the universally recognized way to to patients who they thought might prior to approval and release to the measure duration of survival in benefit and compare the outcomes to marketplace. those of previous patients, who were studies. The paper that put forth this not treated, a method that could In an email to the New York Times, mathematical formula is the most introduce serious bias.” The new trial Dr. Richard Peto, a colleague of frequently quoted paper in research, design, advanced by Meier in the Meier’s and fellow randomization according to the Thomson Reuters mid-1950’s, was, according to Hevesi, researcher, wrote that Meier, Web of Knowledge website, and has “the most rigorous way to conduct “perhaps more than any other been cited more than 35,000 times. ■ REGULATORY UPDATES

95

RU1-in Memoriam.indd 95 9/20/11 1:05 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 DIA 2011:

o facilitate the electronic Terrie Reed, MSIE, first presented throughout the device lifecycle. It regulatoryr submission The State of Electronic Submissions will be applied and traced globally T process,p the FDA Centers for at CDRH: Focus on UDI & Data (not just in the US) through a UDI DrugDr g Evaluation E a & Research (CDER), Standards. Terrie started with a database internationally developed Biologics Evaluation & Research summary review of current CDRH by the Global Harmonization (CBER), and Devices & Radiological eSubmission initiatives, including Task Force. The UDI will facilitate Health (CDRH), continue to work Registration & Listing, Radiation medical device recalls, adverse toward an all-electronic submission Safety Reports & Correspondence, event reporting and postmarket (eSubmission), review, update, and and electronic Medical Device surveillance, and traceability for approval environment. During our Reporting (eMDR). Terrie further potential shortages and substitutions, recent DIA 2011 Annual Meeting, detailed the eMDR Controlled and could even feed into the representatives of these three product Vocabulary that standardizes Agency’s SENTINEL initiative. FDA centers plus other Agency leadership problem input codes for devices, will soon issue a notice of draft provided an update on The State of much like MedDRA® does for drug guidance on the UDI, Terrie noted. Electronic Submissions at CDER, reporting in Europe, and for the CBER & CDRH (session #362). impact of these problems on patients Terrie also asked attendees to think who use them. more strategically about data sharing and exchange. Data is consistently Session chair: Next, Terrie briefly reviewed shared within the regulated industry, Gary M. Gensinger, MBA the fundamental components but it’s time to expand this sharing Deputy Director, Office of and benefits of a Master Data across other government and Business Informatics, CDER Management Plan, which creates healthcare facilities. She referred to a framework for harmonized, DIA’s first Annual Meeting HIMSS Speakers: consistent data that uses a single Interoperability Showcases in the Terrie Reed, MSIE vocabulary and is governed by exhibit hall as an example of this new Associate Director, Informatics, a single plan or group. Also, it expanded vision for data exchange. CDRH identifies the agreed to, standard critical business data (such as item Michael B. Fauntleroy surveyed Michael B. Fauntleroy and event codes, manufacturer and the CBER Electronic Submissions Electronic Submissions device names, etc.) to be shared landscape. He began by reviewing Program Manager, CBER across systems, and it facilitates data the types of electronic submission quality, integration, and stewardship. types that CBER currently accepts: Virginia Hussong eCTD, eIND, and eBLA (roadmap), Team Leader, Electronic Terrie further examined one plus Structured Product Labeling Submission Support, Office of specific component of a Master (SPL). The number of electronic Business Informatics, CDER Data Management Plan, the Unique submissions the CBER receives Device Identifier (UDI), authorized continues to grow, with 12% more Mark A. Gray by the FDAAA of 2007. Similar to a eINDs and 11% more eBLAs received Director, Division of Regulatory drug’s unique identifier, the UDI is in 2010 than in 2009. CBER plans Review Support (CDER/OPI/ a unique, concatenating device and to accept pre-IND and pre-BLA OBI), FDA production identifier created and meeting materials through the

REGULATORY UPDATES REGULATORY maintained by the manufacturer Electronic Submissions Gateway

96

RU3-CDER.indd 96 9/19/11 5:29 PM CDER, CBER, CDRH & State of eSubmissions

(ESG) by the end of 2011. Michael through the ESG is about half of forthcoming version will include reminded attendees that the ESG one percent. Ginny then turned to two-way electronic interaction and will deliver your submission to your current electronic projects, which the ability to cross-reference and use reviewer in as little as ten minutes, include: An update of eCTD Module submitted documents, to enhance but submissions that are manually 1, implementation of new eCTD current RPS capabilities: Handling processed generally take 48 hours to validation codes and new viewer/ bundled, global, or grouped get there. validation software, and Regulated supplements; exchanging additional Product Submission (RPS), which submission metadata such as contact Next, he described the recently creates one standard exchange information, submission status, redesigned, enhanced CBER message that can be used for the and submission content/purpose; Electronic Document Room submission of any regulated product. and handling multi-component (EDR), which stores content documents, all according to ICH related to an application (not only The eCTD Module 1 update and regional (including Europe) the submission but related CBER will reorganize and update requirements. correspondence) plus other content Administrative Information to that may not relate to a specific include new submission types, Mark then explained that the system application (such as training submission numbering, and the has been constructed so that an materials). These enhancements ability to apply one submission applicant can build an eCTD lifecycle include full-text searching and a to multiple applications. Another that started using the eCTD3.2.x records management application important feature is that this upgrade specification and continues using for the schedule and disposition will allow the CDER Division of eCTDv4 – what you might call of official records. Michael also Drug Marketing, Advertising & the “migration” from v3 to v4. No described the eSubmitter pilot Communications (DDMAC) to applicants should be required to program currently underway in the accept eCTD submissions, too. FDA resubmit data in eCTDv4 that CBER Office of Blood Research & will issue Guidance Updates and was previously and successfully Review: eSubmitter is a software offer training workshops when submitted using v3. So if your application comprised of question they’re ready to release and company has not implemented and answer data capture forms which implement this update. eCTDv3 because you were waiting use business rule logic to capture Implementation of new validation for v4, don’t wait any longer – submission content and shape it into codes and software, which implement the eCTD and stop

.pdf or .xml format. It was initiated incorporates comments received submitting paper! REGULATORY UPDATES for small companies who don’t have from related tool vendors, is the manpower required to format currently scheduled for November eCTDv4 is already being tested, and validate electronic submissions. 2011. and will continue testing through August 2012. Subsequent activities Ginny Hussong’s presentation on To conclude this session, Mark Gray will include the development of The State of Electronic Submissions previewed the electronic Common implementation guides for using RPS at CDER began with her review Technical Version (eCTD) v4 (Next to create eCTD messages at both the of the eCTD and data submittal Major Version). Mark first explained ICH and regional levels. FDA’s target tools currently in use. She was that the eCTDv4 is a subset of implementation for accepting RPS- happy to report that the rate of RPS implemented specifically based eCTD submissions is the first rejections for submissions received for human pharmaceuticals. This quarter of 2014. ■

VOL 3 ISSUE 5 GLOBAL FORUM 97

RU3-CDER.indd 97 9/19/11 5:29 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 Searching for Answers and Relief: A Mother & Daughter’s View of the Clinical Trial Experience

nswersn start with research arteries were extremely narrow in medications to help move the bile anda from the very places; a lung transplant might be through her system and alleviate A beginning,b the Hahn family necessary. the itching, but nothing seemed to needed answers. an help. Alaina scratched till she bled The Hahns were beside themselves. and started getting thinner. By the In January, 1991 four-month-old “After the heart catheterization, time she entered elementary school Alaina Hahn was diagnosed with we just went out in the parking lot she was embarrassed to wear shorts Alagille Syndrome, a rare disorder and cried,” Cindy recalls. “It was all because her legs were constantly in which a person has fewer bile or just so unbelievable to us. We kept covered with Band-Aids. hepatic ducts inside the liver than thinking, ‘They can’t be talking about normal. The deficiency leads to a our child.’” “I was so itchy it was impossible to sit build up of bile in the liver and liver still and concentrate in school,” she damage. Alagille Syndrome can After all, their baby was beautiful remembers. “The kids were always likewise cause severe damage in the and perfect. Yes, she spit up a lot teasing me. ‘Why are you so small? heart, kidneys and blood vessels, of formula and she sometimes Why are you so skinny? Why are you abnormalities in the spine and eye, looked a bit yellow -- a passing always wiggling around and itching?’” and characteristic facial features. comment about Alaina’s coloring had In addition to jaundice caused by prompted Cindy to take her daughter Alaina was miserable and her the bile buildup, Alaina was also to the doctor in the first place -- but mother wanted answers. So, in 1998 diagnosed with a heart murmur. certainly the doctors’ concerns were Cindy enrolled Alaina, then eight, overblown. The Hahn’s supplemented in a study being run by Children’s After consulting with doctors at her meals with a thick concoction of Hospital of Philadelphia designed Seattle Children’s Hospital, that was yogurt, milk, eggs and fruit because to help researchers understand all the information Alaina’s mom, doctors said she needed the extra how pancreatic function affects the Cindy, had about Alagille Syndrome. nutrition, but the baby hadn’t been growth and nutritional needs of prescribed any medications and children with Alagille Syndrome. “They basically said, ‘We have a seemed healthy. Participation involved three trips to name for this disorder but we don’t Philadelphia, but only one invasive know what it means,’ ” says Cindy. Then, on a morning in 1992, Cindy procedure: Alaina would have to “They didn’t have any idea about went to get her daughter out of her have a nasogastric tube inserted from life expectancy and, although they crib and found her covered in blood. her nose to her small intestine during said she might eventually need a Horrified, she discovered Alaina had the first clinic visit. liver transplant, they also said that scratched her ankles raw. When she it would only fix the liver, but not changed Alaina’s diaper, Cindy found Watching the procedure was torture everything else associated with the her stool was cream colored. for Cindy, who felt frustrated and syndrome.” powerless. Alaina gagged repeatedly Suddenly, Alagille Syndrome seemed as researchers struggled to direct the Doctors’ pronouncements became very real. tube to the right spot in her intestine. increasingly dire. When Alaina was 18 months old, doctors performed The build-up of bile in Alaina’s Fortunately, most of the study

PATIENT PERSPECTIVE PATIENT a cardiac catheterization procedure. blood was causing her skin to itch involved more mundane This showed Alaina’s pulmonary unrelentingly. Her doctor prescribed requirements. Cindy had to keep 98

PP1-Hahn.indd 98 9/19/11 5:37 PM a meticulous food log and collect “The ostomy companies don’t make She’s not cured: doctors continue to Alaina’s stool. “It wasn’t enough products for biliary stomas because monitor her liver function closely to say Alaina had five ounces of so few people have the surgery and and her bilirubin has begun to inch macaroni and cheese,” she says. “The the bile kept dissolving the adhesive up. Consequently, Alaina and Cindy researchers had to know what brand on Alaina’s ostomy bag,” Cindy says. continue to watch for promising it was and what type of milk I used Alaina was having to change her trials. Alaina hopes to participate and whether I made it with butter or ostomy bag multiple times a day and in a natural history study being margarine.” couldn’t be sure the adhesive would conducted by the Childhood Liver make it through recess. Ultimately, Disease Research and Education Although participation was a after a lot of trial and error and Network aimed at collecting data hassle, Cindy was excited to meet helpful guidance from one of the to facilitate a better understanding leading experts in the field and glad ostomy companies, they found a of Alagille Syndrome and other that she and Alaina were helping urostomy pouch that fit the bill. liver disorders. Cindy, as president scientists better understand Alagille and CEO of the Alagille Syndrome Syndrome. In the months following the surgery, Alliance, is working to promote Alaina’s itching not only eased, she additional research. But Alaina continued to suffer from unrelenting itching. In Both Alaina and her mom 2002, when Cindy heard about know that neither Alagille a surgical trial being conducted Syndrome nor science stands at Children’s Memorial Hospital still. Alagille Syndrome is in Chicago, she knew she had insidious. Cindy notes, “New to give 11-year-old Alaina the things crop up all the time. option of participating. You feel like things are going OK and then boom something The study was designed to happens.” understand the effects of partial external biliary diversion on The only answers, she knows, growth and itching in children will come from research. But with Alagille Syndrome researchers need to share who suffered from constant, those answers – even if they debilitating itching and did are only partial—more readily. not respond to any medical Cindy laments that what she’s therapies. Alaina would have learned about the outcomes to undergo surgery in which from both studies in which doctors would remove a six-inch has Alaina participated, she section of her small intestine and has found out on her own. use it to create a conduit from No one has ever notified her her gall bladder to an ostomy when a paper on the research pouch attached to her abdomen. has been published. “It’s very For the rest of her life she would frustrating not to know what have to wear an ostomy pouch to the outcome of a trial was,” collect her bile and there was no she says. “Participants and guarantee that the operation would began to put on weight and grow. their families want to know.” alleviate her itching. Undaunted At the time of the surgery Alaina’s

by the risks, Alaina was the first growth had stalled. She measured After all, they’re the ones for who PATIENT PERSPECTIVE participant to sign up for the trial. only 4’7” and weighed just 60 answers matter most. ■ pounds. In the wake of the surgery, The results, Cindy says, were nothing she began growing and gaining short of miraculous. Within 24-hours weight. of the operation Alaina’s itching This story is from a series of articles began to abate. For the first time in Today, Alaina is a 20-year-old college created by CISCRP as part of their nearly a decade, she had relief. student at the University of Oregon. educational awareness campaign to She tires easily and does best if she increase public understanding that But now she faced a new challenge: gets at least 10 hours of sleep at those who volunteer to participate finding an ostomy bag suited for her night; but worries about a potential in clinical trials are genuine needs. lung transplant have subsided. “Medical Heroes.”

VOL 3 ISSUE 5 GLOBAL FORUM 99

PP1-Hahn.indd 99 9/19/11 5:37 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 DIA PUTS THE PATIENT PERSPECTIVE IN THE CENTER OF IT ALL

My DIA pediatric study design. Of note was with representatives of CROs, IT the presentation by Barry Magnum, companies and other businesses Patient PharmD (Duke University Medical and organizations, I snuck in a free Center) in Monday’s session entitled, neck massage, posed for a caricature, Fellowship “Risk Assessment Process for savored a smoothie or two, and Experience Pediatric Protocol Development.” entered for a chance to win iPods, His practical perspective to pediatric iPads, and other items. One of my research and common sense favorite giveaways was a blue pen questions that would be obvious to topped by a bobbing crazy-haired guy Cindy L. Hahn a 2011 DIA Patient any parent – Can a child swallow who laughs hysterically when pressed. Fellow is the President & CEO those pills? How does that drug of Alagille Syndrome Alliance taste? Do you need that much blood? I would participate in the DIA in Tualatin, Oregon. She can be –may be easily overlooked by the Patient Fellowship Program again reached at 503.885.0455 or investigator, and could make the in a heartbeat. It was fantastic to be [email protected]. difference between a successful and a a part of the inaugural year and to failed trial. help shape the experience for future Attending the 2011 DIA Annual Fellows. I thank DIA wholeheartedly Meeting as a Patient Fellow was an On Tuesday, I shared my daughter’s and wish future Fellows an experi- awesome opportunity on numerous story, gained new insights from co- ence equally as incredible to mine. levels. panelists, and was encouraged by the multitude of audience questions DIA Puts The Patient Fellowship Program in the “Voice of the Patient” session. plucked me from Oregon, thousands Organized by CISCRP (Center for the Patient of miles away from the political and Information & Study on Clinical regulatory hub of Washington DC, Research Participation), this panel Perspective and gave me the opportunity to was designed to help professionals in the Center network with 14 other Fellows from improve study protocols by across the country. It was inspiring keeping the patient’s experience of it all to exchange ideas with individuals in mind. It was well attended and representing a wide spectrum of enthusiastically received, and I felt Lorren Sandt is the Executive Director patient organizations, and the chance honored to be chosen as a speaker. of the Caring Ambassadors Program, to interact with and learn from them Inc. located in Oregon City, OR. She was truly energizing. From start to finish, including our can be reached at 503-632-9032 or final Patient Advocate Breakfast on [email protected]. The Patient Fellowship Forum Thursday morning, DIA leadership on Sunday was an eye-opening was readily accessible and inviting. Though truly excited at being chosen introduction to patient advocacy President Richard Day, Program to receive the Patient Fellowship opportunities in a variety of forums. I Chairperson Kenneth Getz, incoming Award at the DIA Annual Meeting, it was especially engaged by the Patient President Yves Juillet, Worldwide was upon attendance at the conference Representative Program at the FDA, Executive Director Paul Pomerantz, that I realized the real gift I had which offers an avenue for patients and others, completely embraced the been given. Because, it was not until and family members directly affected initiative to involve patient advocates I was in Chicago, immersed in the by a serious disease to contribute in DIA. They were visible, engaging, numerous workshops, networking their unique perspective to product and genuinely intrigued by our with fellow advocates, exploring all or therapy review. thoughts and opinions. the possibilities at the meeting, that I sensed a different paradigm. Because I am particularly interested Amidst it all, I found time to

PATIENT FELLOWS PATIENT in pediatric diseases, I attended circulate through the exhibit area, In my experiences, patient advocates several subsequent sessions on which was great fun. Besides talking are invited to events only because 100

PF-Patient Fellows.indd 100 9/19/11 5:39 PM DIA 2011 WAS OUR FIRST ANNUAL MEETING TO OFFER PATIENT FELLOWSHIPS FOR REPRESENTATIVES OF PATIENT ADVOCACY GROUPS. THREE PATIENT FELLOWS REFLECT UPON THEIR DIA 2011 EXPERIENCE IN THE FOLLOWING ARTICLES.

someone thinks it is a nice thing to development for chronic, ultra-orphan creative convergence between patient do; they are rarely truly an integral autoimmune diseases. Ms. Stuart groups and the drug industry with its part of a conference of this magnitude. lives in Sacramento, CA. She has a law opportunities and hope. The Patient At DIA, the Patient Advocacy Fellows degree and is a certified mediator. Fellowship Group was highlighted and were integrated into the entire event. encouraged to participate fully. From the Board Chairs (past and The International Pemphigus present) to the event organizers, DIA Pemphigoid Foundation (IPPF) Tuesday’s Forum focused on the really put the patient perspective participated in the DIA’s first Patient “Voice of the Patient” and DIA where it belongs – in the center of Fellowship Program, meant to enhance attendees got a real taste of patients’ it all. the participation of patient advocacy perspectives on clinical research. We groups at DIA in order to develop, discussed dis-incentives to patients As a patient advocate, it was strengthen and support patient to participate, such as scary media fascinating to learn about the group collaboration with health care stories, uncertainty about how the enormous complexity as well as the policy makers, medical professionals, process works, lawyers and legalese in number of companies and regulatory industry representatives and academia. complicated forms, fear from family agencies that are involved in members, fear that they might not get developing and taking to market a The IPPF was one of 15 patient a “real” medicine, and the time and/or new therapy or medical device. This organizations selected out of over 50 expense involved. insight will help us when we are applicants to receive a grant for all working with patients frustrated by attendance costs. I attended along And yet, everywhere I turned I heard the lack of, or price of, new therapies with CEOs and other representatives patients speaking out about how much or medical care. of patient groups such as the they had gained from participating Myasthenia Gravis Foundation and the in trials. In the most dramatic cases The Patient Fellowship Program Pancreatic Cancer Action Network. I heard stories of some who got was a fantastic experience and one The goal for everyone was to try to better medical care than they could that I hope many more advocates strategize ways that we can bridge the have afforded and some who used will be invited to participate in at gap between what patients hope and treatments they otherwise wouldn’t future meetings. The networking fear about clinical trials. have been allowed to receive. was amazing. It is great to step out of our focused perception of a DIA and our liaison, Donna Mayer, Many of our Patient Fellows were certain disease, and instead meet had everything thoroughly prepared included on panels and I spoke other advocates and health care for our group. Our smaller cohort on Wednesday regarding patients’ professionals, and learn from each stayed at the Palmer House, my experiences with clinical trials. On a other how we can better serve our favorite Chicago hotel, where I more mundane, but extra powerful patients. Thank you DIA. hadn’t been since graduating from level, participants talked about how law school many years ago! On good it made them feel to know DIA Sunday we participated in a training that they were improving science and networking day in preparation and, therefore, improving hope for Enhances for our involvement in the larger anyone who comes after them– a DIA conference. We also worked in true sense of their efforts on behalf PATIENT FELLOWS Patient groups with university and industry of a wider community. Through Dia’s Voice researchers to discuss how they might efforts to include actual patients improve things for patients who are and patient advocates, highlight the participating in clinical trials. opportunities for collaboration, and provide us training and resources Molly Stuart is CEO of an health Monday’s Opening Plenary session to make the most of our connection advocacy non-profit, working to focusing on the Convergence of opportunities, DIA has truly set us promote research, awareness and Science, Medicine and Health was the all up to better hear the “Voice of the support for drug and medical perfect mirror to our group’s sense of Patient.” ■

VOL 3 ISSUE 5 GLOBAL FORUM 101

PF-Patient Fellows.indd 101 9/19/11 5:39 PM GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

COMPUTERIZED SYSTEMS IN CLINICAL RESEARCH CURRENT DATA QUALITY AND DATA INTEGRITY CONCEPTS

Reviewed by R. L. Chamberlain, Ph.D.

omputerizedo Systems The answers to these questions in Clinical Research – need to be documented and will “C CurrentC Data Quality and contribute to the quality and Data Integrity Integ Concepts,” known integrity of the data. throughout DIA as The Peach book, was prepared as a follow-up to the Red Computerized Systems in Clinical Apple II book entitled, “Computerized Research Systems Used in Non-clinical The Peach discusses the steps

Research.” These books are both COMPUTERIZED involved in the conduct of a clinical SYSTEMS IN Current Data intended to help those working with CLINICAL Quality and Data trial and addresses the information computerized systems to be RESEARCH Integrity Concepts that is generated and has to be A continuation of the Red Apple effort in the more compliant and to increase the clinical arena and designated as “Peach” managed at each step. In most

quality of the data and, therefore, Published by cases, a computerized system is the results of clinical and non-clinical used to manage this information. 800 Enterprise Road, Suite 200 © Copyright 2011 Drug Information Association research. Horsham, PA 19044, USA ISBN 978-1-4507-7152-8 When talking about the quality and Data Quality and Data Integrity integrity of the data, it is important The emphasis today is often on the example, was it a sitting or standing to understand that there are two computerized system and there is a blood pressure? did the subject fast aspects to that. The first is the tendency to not pay enough attention before the blood sample was taken? quality of the value of the data as to the processes of observing and was discussed above; and, the collecting the data that will be When the data is observed, such second is the quality of the entered in the computer system. questions can arise; a few of them are computerized systems used to The Peach book covers the conduct store and manage that data after of clinical trials and, in particular, t
Is the procedure for observing the value is obtained. focuses on the quality and the the data documented? integrity of the data. The Peach covers both of these t
Was the person performing the topics. It introduces the reader to The data collection process starts observation trained? the concepts of quality, integrity, and with a medical person either risk. It applies these principles to observing or, more often, measuring t
Are there records of that both the data and the computerized a “value” for the subject. For example, training? systems. the subject has a blood pressure; the subject has a cholesterol level; and/ t
Was an instrument used to make The quality of the data can be or, the subject has some other value the observation? summarized by looking at the that needs to be observed. Once that ALCOA characteristics. The value is determined, the value itself t
Does the instrument need quality of the computerized system has certain other characteristics calibration or regular is addressed by applying

BOOK REVIEW that need to be managed. For maintenance? Computerized Systems

102

BR2-Peach.indd 102 9/19/11 5:42 PM BOOK REVIEW 103 9/19/11 5:43 PM

GLOBAL FORUM GLOBAL 5 3 ISSUE VOL ■ is is clinical n iiiiiiiiiiiiii i ddddddddddddddddd ved in n edededed v ol lvlv vvv ooooooooooooo nvnvnvnvnvnvnvnvnvnvnnvnnnn vo edata R. L. Chamberlain, Ph.D., a member Forum of the Global Editorial Board also contributed and of the Peachto the compilation book. can be reach at [email protected]. He Conclusion all involved in clinical at If you are research involved in not and are data, the only recording but also observing data, the Peach the then should be a required reference. You can purchase your own copy of Computerized Systems in Clinical Research: Currently Data You Click through the im- Quality and Data Integrity Concepts through our DIA online marketplace. homepage, or select “Publications: age of the book cover on the bottom of our www.diahome.org will need to to make your purchase. You Other Products & Services” from the left navigation bar, have forgotten your login with your DIA username and password to access your account. If you username or password, please use our website login reminder (https://www.diahome.org/DIA- Home/Common/Templates/LoginReminder.aspx). Electronic Medical Records electronic of The implementation medical (EMR) records systems in hospitals take some could The uselessons Peach. from the of private medical in records clinical research is a growing topic of discussion. recording Simply medical record a person’s electronically is only a small partclinical of conducting quality the research; however, recording and integrity of that process has impact on the a large results of clinical research. Validation – Part 11 principles – Validation thoseto systems. facedAnyone with managing medical on the information can principles use the in computer Peach. the BR2-Peach.indd 103 GLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5 DIA Members on the Move

DIA is committed to improving the numerous professional organizations Rheumatology in the US, a Fellow of professional performance of our including the American Pharmacists the American College of Physicians members and volunteers through our Association, the American Society of and the American College of educational and networking forums. Health-System Pharmacists, the Rheumatology, and is a member of Please join us in congratulating the Pennsylvania Pharmacists multiple professional societies in the following DIA members for their Association, and the Pennsylvania US and abroad.Professionals Society recent professional accomplishments: Society of Health-System and the American Academy of Pharmacists, and currently serves on Neurology. Dr. Surinder Kher has been the Board of Directors of Christian appointed Chief Executive Officer, Pharmacists Fellowship Rebecca Daniels Kush, PhD, was Asia, for Ecron Acunova (India). International. Dr. Hussar has also appointed to represent the research Dr. Kher served as a member of the Board of community on the HIT Standards previously served Trustees for the American Committee, a federal advisory com as Senior Vice Pharmacists Association, on the mittee that makes President of Board of Directors of World Vision, recommendations Clinical and and is a Past President of the on standards, Regulatory Pennsylvania Pharmacists implementation Operations of Association and of DIA. He earned specifications, and Vanthys. Dr. Kher his BS, MS, and PhD in Pharmacy, certification earned his all at the Philadelphia College of criteria, to the medical degree from the Medical Pharmacy and Science. National Coordi- College, Srinagar, India, and nator for Health practiced medicine for six years Tomas S. Bocanegra, MD, has been IT. Dr. Kush is a Founder and the before entering industry. He also appointed Executive Vice President current President and CEO of the serves as Chair of the National of Development for Pozen, Inc. Dr. Clinical Data Interchange Standards Clinical Trials Taskforce of the Bocanegra previously served as Consortium (CDISC). She has more Federation of the Indian Chamber of Senior Vice President, than 25 years of clinical research Commerce and Industries. Development, experience through working with the for Daiichi US National Institutes of Health, Daniel A. Hussar, PhD, was named Sankyo Pharma academia, and pharmaceutical 2012-13 Honorary President of the Development.He companies in the US and Japan. Dr. American Pharmacists Association. obtained his MD Kush previously served on the DIA Dr. Hussar serves degree from, and Board of Directors, and helped estab- as the Remington did his internal lish the DIA eClincial SIAC. She Professor of medicine earned her PhD in Physiology and Pharmacy at the training at, Pharmacology from the University of Philadelphia Cayetano Heredia University in California (UCSD) School of Medi- College of Lima (Peru), and completed his cine in La Jolla (CA). ■ Pharmacy at the fellowship in rheumatology at the University of the University of South Florida College

MEMBERS ON THE MOVE Sciences in of Medicine. Dr. Bocanegra is Board Philadelphia. He is a member of Certified in Internal Medicine and 104

MOM-members on the move.indd 104 9/19/11 5:45 PM Dr. Rick Turner, Editor-in-Chief of the Drug Information Journal, recently attended the 2nd DIA DIA President Featured Japan Cardiac Safety Meeting, held in Tokyo on September 5th Interview with Pharma IQ and 6th. While in Japan he took the opportunity to meet with Key Opinion Leaders and regulators from the Japanese PMDA. One of his meetings was with Professor n July 21, Pharma IQ posted a video interview Yuji Kumagai, Kitasato University with Dr. Yves Juillet, DIA President, who spoke to Hospital East, and Executive Direc- O tor, Kitasato Academic Research Pharma IQ correspondent Andrea Charles about Organization (KitARO). Dr. Turner the top three regulations impacting the pharmaceutical invited Professor Kumagai to write an Expert Commentary for industry in 2011 – 2012. In this interview, recorded at DIA's the Journal, and to participate in several DIA-related activities in the 47th Annual Meeting in Chicago, Dr. Juillet discusses DIA's future. ■ top priorities in the next twelve months, why convergence is so important in the pharmaceutical industry, the impact of convergence on competition, and an overview of the role that patients play in their own health care. Watch it online at http://www.pharma-iq.com/regulatory-legal/videos/. ■ MEMBERS ON THE MOVE

ON THE MOVE? LET US KNOW If you’re an active DIA member and would like to share your professional or career news with other members in our Global Forum, please send your announcement (and high-resolution digital photograph, if you have one) to [email protected]. All submissions are subject to DIA editorial review and approval. Please remember to keep your DIA member profile current by logging into “My DIA” and updating your contact information to reflect your new job title, employer, or email address, too.

VOL 3 ISSUE 5 GLOBAL FORUM 105

MOM-members on the move.indd 105 9/19/11 5:45 PM MARKETPLACEGLOBAL FORUM OCTOBER 2011, VOL 3 ISSUE 5

Local Touch, Global Reach Conducting study visits in the patient’s home for:      U Faster patient recruitment U Better compliance      U Higher retention rates    email: [email protected]    R   Tel: +1 847 282 3280 www.globalcarect.com

The HHS Supply Service Center is an operating division of the Department of Health and Human Services offering pharmaceuticals, Global Patient Enrollment Solutions Empowering patients and driving sites to medical supplies, logistical ÊÊUÊ*>̈i˜ÌÊ,iVÀՈ̓i˜Ì produce clean & complete clinical data support and clinical trial services to other government ÊÊUÊ*>̈i˜ÌÊ,iÌi˜Ìˆœ˜ facilities in the U.S. and ÊÊUÊ-ˆÌiÊ-iiV̈œ˜ throughout the world. ÊÊUÊ ˜Àœ“i˜ÌÊi>ÈLˆˆÌÞ HHS Supply Service Center ÓÇÓÊ °ÊÀœ˜ÌÊ-ÌÀiiÌ]Ê ÜÜÜ°ˆ˜Vˆ˜ˆÝ°Vœ“Ê Building # 14 Phone: (800) 642-0263 Ste. 500 ˆ˜vœJˆ˜Vˆ˜ˆÝ°Vœ“ Perry Point, MD 21902 Fax: (410) 642-2047 7ˆ“ˆ˜}̜˜]Ê ÊÓn{ä£ ­™£ä®ÊÎÎӇÓÈnÓ 215-609-4378 www.greenphire.com http://sscweb.psc.gov

Nova Language Services is a full service translation provider to the international health sciences sector. We offer a professional personal service at Introducing competitive rates. The future of EDC...available today We are ISO 9001:2008 and  A cloud-based, next-generation eClinical solution UNE-EN 15038:2006 accredited  Quickly and easily build your own studies  A low cost, software-as-a-service (SaaS) solution innovation at work Schedule an iMedNet Demo www.nova-transnet.com [email protected]  (866) 258-2735  mednetstudy.com Tel: +44 (0) 1908 262 808

RWD’s infoMaestro™ Integrated Medical

Communications Mobilize your trial to improve recruitment and Solutions 3.0 retention with PCM TRIALS’ own Certified Australian Clinical Research Mobile Research Nurses (CMRN). CMRNs take Sites & CRO Services Our document assembly solution, based your trial to the subject and can complete assessments, source documentation, drug on SharePoint 2010, continues to be administration, specimen collection and Contact: Julie Mellowes processing with the same quality as on-site visits. the leader in enterprise-class medical [email protected] information management solutions. www.pcmtrials.com www.pretium.com.au MARKETPLACE

106

Market Place.October2.indd 106 9/21/11 12:24 PM Trust Sharp to be your single source for contract packaging services.

[email protected] www.sharpcorporation.com

THE GLOBAL REGULATORY LANDSCAPE AT YOUR FINGERTIPS go.thomsonreuters.com/request_info

©2011 Thomson Reuters. All rights reserved.

MSN Clinical Research Staffi ng: Making the Right Match, Every Time. 877.605.2500

!"#!$"%"!! CLINICAL RESEARCH &' MSNClinicalResearch.com

Empowering patients and driving sites to EastHORN Clinical Services in produce clean & complete clinical data CEE Headquarters rease patient satisfaction ve patient protocol compliance rease patient retention EastHORN Clinical Services in CEE Tel.: +420 244 462 241 rry risk 140 00 Praha 4 Fax: +420 244 462 271 Czech Republic 215-609-4378 www.greenphire.com [email protected] MARKETPLACE

Full-service CRO serving the pharmaceutical and biotechnology industries in the areas of clinical operation, data management, biostatistics, medical writing, and regulatory submissions.

725 Concord Avenue Cambridge, MA 02138 [email protected] Phone: 617-844-0223 www.PROMETRIKA.com

VOL 3 ISSUE 5 GLOBAL FORUM 107

Market Place.October2.indd 107 9/21/11 12:24 PM Join today and take advantage of DIA member benefits!

GAIN VALUABLE INFORMATION. DIA’s outstanding resources include the scholarly, peer-reviewed Drug Information Journal, as well as the DIA Global Forum, Global Regulatory Affairs Digest, and DIA Dispatch.

NETWORK AND BUILD PROFESSIONAL RELATIONSHIPS. Attend a DIA conference or training course, join a Special Interest Area Community (SIAC), gain access to our new DIA ConneX Professional Networking Community. DIA ConneX is a members- only professional networking community featuring easy-to-use collaboration and communication tools.

DEVELOP YOUR CAREER. Speak at a meeting, develop an abstract, lead a committee, accumulate CE credits.

Join at www.diahome.org/membership.

Market Place.October2.indd 108 9/21/11 12:24 PM Network with Professional Colleagues Anywhere Anytime!

DIA ConneX You

DIA’s new members-only social networking-style website is a vital resource for professionals like you looking to connect with others in your

field and improve your Thousands of your colleagues will be part job performance. of DIA ConneX, so don’t get left behind.

How Can DIA ConneX Help You? • Get answers to on-the-job questions • Access shared resources such as white papers and articles • Network with thousands of your colleagues worldwide

Get connected at www.diahome.org/DIAconnex.

!!"#%  , ,  GFCovers and Spines.oct.indd 3 9/20/11 3:11 PM Your Language. Our Focus. Corporate Translations: The preferred supplier of translations to the life science industry.

- Translation - Multilingual Desktop Publishing - ISO 9001:2008 Certified - Linguistic Validation - Translation Memory Databases - EN 15038:2006 Certified - Harmonization - Certifications of Accuracy - Job Status Tracking - Back Translations - Design and Printing - Secure Document Libraries - Website Localization - Audio Video Voiceovers - 24/7 Customer Service

77 Hartland St. East Hartford, CT 06108 Tel: 860-727-6000 Fax: 860-727-6001 www.corptransinc.com

CTiGFCovers 2010 DIAand GlobalSpines.oct.indd Forum AD 4 February indd 1 9/20/111/21/11 3:11 2:14 PM PM Do not print rule

GFCovers and Spines.oct.indd 5 9/20/11 3:12 PM