October 2009

Center for Clinical and Translational Science

e-Newsletter

Center News New Certificate Program in Clinical and Translational Science Graduates First Class By Angela Slattery In September 2008, a new Certificate Program in Clinical and Translational Science began at . Eighteen students from across campus participated in the inaugural class. In June 2009, all of the program’s students graduated and received a Certificate in Clinical and Translational Science from the university. The Certificate Program, which is sponsored by the Center for 2009 Inaugural Certificate in Clinical and Translational Science Class Clinical and Translational Science or his own hypothetical human subjects The protocols that were submitted (CCTS), was developed in collaboration protocol, including an informed consent in fulfillment of the requirement of with students and postdoctoral fellows form. To further familiarize the students the course were of exceptionally high to provide trainees with an introduction with the protocol review process, the caliber and offered insights into the to the principles and practices of clinical students then functioned as a mock IRB, clinical research interests of the talented and translational research. reviewing each of the protocols and group of investigators who enrolled in The Certificate Program is a one year offering suggestions to insure the optimal the program. Dr. Barry Coller, director program that consists of two courses. design and the greatest protection of the of the Certificate Program stated, Each student was required to create her human subjects that would participate. (continued on page 2)

CCTS and Clinical Directors Network Successfully Complete First Collaborative Project By Angela Slattery

In the fall of 2008, through the history phenotyping system. The goal 3) identifing patients whose laboratory Advisory Committee on Community of this initial project was to validate data and bleeding symptoms are Engagement and Recruitment (ACCER), the instrument. The eventual goal is discordant for future gene-gene and gene Clinical Scholar Dr. Andreas Mauer to provide the system to all authorized environment studies, and 4) assessing the was introduced to Dr. Jonathan Tobin, investigators with Internet access so that medically optimal and most cost-effective President and CEO of the Clinical they can have the opportunity to collect way of deciding whether to order an Directors Network (CDN). CDN is a bleeding history data in a standardized extensive laboratory evaluation. not-for-profit network that supports way and store the information in a single, Dr. Mauer obtained approval to enroll community-based health centers, uniform database. This database would 500 normal healthy participants in this including their patients, practitioners, aggregate deindentified data obtained by study from the Institutional Review and other affiliated organizations. many different investigators and would Board (IRB) and Advisory Committee Community health centers work with be freely accessible to investigators for Clinical and Translational Science CDN to assist with projects and facilitate worldwide. Potential applications of the (ACCTS). CDN was an ideal partner community engagement. system include: 1) improving diagnosis for this project because it could assist in of bleeding disorders, 2) identifing the Dr. Mauer and his mentor, Dr. Barry recruiting participants from community fewest number of questions needed to Coller, were interested in developing settings and their participation would exclude the presence of a significant and validating a Web-based bleeding broaden the diversity of the population bleeding disorder with high probability, (continued on page 2)

1 New Certificate Program in Clinical and Translational Science Graduates First Class (continued from page 1)

“I am extremely impressed with the University and to demonstrate scientific/ scores for the Certificate in Clinical scientific and medical sophistication technical methods that are currently and Translational Science program as a of the projects and the techniques employed to address critical problems whole, 100% of the responders stated proposed; we are continuing to assess in human biology. Another purpose they would recommend the program whether some of these protocols might for the course was to familiarize the to their peers and felt that the program be performed in our hospital. This is an students with the Rockefeller University should continue to be offered to the exciting possibility for us.” personnel available to aid them in Rockefeller community. One interesting applying these cutting edge technologies. indication of the impact of the program The first course, Introduction to Clinical The final project for the course had the is that two of the students decided to and Translational Science, was offered students return to the protocols they had alter their career paths and apply for in fall 2008. It was twelve weeks long developed in the Introduction to Clinical admission to medical school. and consisted of two 90-minute lectures and Translational Science course and per week. The first lecture of each week In August of this year, Dr. Coller enhance the protocols by adding new described an important element in reviewed the course materials, student techniques such as bioimaging, high clinical and translational science (e.g., projects, and evaluations for the throughput screening, or gene targeting biostatistical considerations, human Certificate in Clinical and Translational that would augment the research design subjects protection, study design, etc.). Science Program with Dean Sid and facilitate their ability to test their The second lecture of each week was a Strickland and Assistant Dean Emily hypotheses. scientific presentation by a Rockefeller Harms. Based on the rigor of the University investigator explaining her Both courses received high evaluation courses, the quality of instruction, and or his research, emphasizing the element marks by the students, with 100% of the level of participation required, the taught at the beginning of the week. the students reporting that they would Dean’s Office decided that both courses recommend the courses to others, will now be offered for credit. CCTS is The second course in the program, nearly 75% of the students stating planning to offer the Certificate Program Introduction to Scientific Techniques the course changed their views about in alternate academic years based on in Clinical and Translational Science, clinical and translational research, and the assessment of likely enrollment and began in March 2009. Led by Drs. Sarah approximately 67% of the students faculty availability. The next Certificate Schlesinger and James Krueger, the goal stating that the course made them more Program is scheduled to begin in the fall of this course was to introduce students likely to conduct clinical or translational of 2010. to core resources available at Rockefeller research. In terms of the evaluation

CCTS and Clinical Directors Network Successfully Complete First Collaborative Project (continued from page 1)

studied. Drs. Coller and Mauer visited and interviewing patients, as well as on Thrombosis and Hemostasis meeting the Jersey City site together, met with educating the staff at the sites about the in Boston. Dr. Tobin, Dr. Mauer, and Dr. the staff, and learned from them about project. The time from study approval to Coller are working together on future the bleeding (hemostasis) problems study completion was approximately 10 collaborations. Dr. Mauer stated that, they face in their practice. Dr. Coller months; the Clinical Research Support “Dr. Tobin has been extremely helpful provided a lecture on hemostasis for Office (CRSO) recruitment program, with so many aspects of this project. I primary care physicians and described with the outstanding assistance of the look forward to future collaborations the goals of the project. Ultimately, CDN staff, made this accomplishment with Dr. Tobin and CDN.” from the 500 total participants in the possible. study, 365 were seen at Rockefeller In addition to CDN’s role in assisting University Hospital, 75 were seen at If you would like to contact Dr. Tobin to with participant recruitment, the Metropolitan Health Center in Jersey discuss whether your project may benefit from City, NJ and 60 were seen at Newark project benefited enormously from Dr. collaborating with CDN, you can contact him Community Health Center in Newark, Tobin’s expertise in study design and at [email protected] or call 212-382- NJ. Dr. Mauer oversaw the project and statistical approaches. Data from the 0699 ext. 234. Dr. Chamanara Khalida from CDN study were presented by Dr. Mauer in played an important role in recruiting July 2009 at the International Society

2 Clinical Scholars Program Graduates First Class of Master’s Degree in Clinical and Translational Research By Angela Slattery and Jennifer Spada

In June of this year, the Clinical Scholars program had four graduates who were the first to receive the new Master’s Degree in Clinical and Translational Research. The KL2 Clinical Scholars program, which is supported in part by the Rockefeller University Clinical and Translational Science Award (CTSA), is a training experience designed to prepare physician-scientists and select doctoral level PhD investigators for independent careers in clinical and patient-oriented translational research.

Dr. Marina Caskey, Dr. Edgar Charles, Left to right: Dr. Barry Coller, Dr. Edgar Charles, Dr. Marina Caskey, Dr. Allegra Grossman, and Dr. Lisa Dr. Lisa Neff, and Dr. Allegra Grossman Neff were honored at a graduation dinner celebration, surrounded by program, Dr. Caskey will continue whether vitamin D repletion improves other Clinical Scholars, mentors, and her work on the HIV-1 vaccine in Dr. insulin resistance. Dr. Grossman is administrative staff. Each graduating Steinman’s laboratory. currently a Senior Medical Scientist at scholar was acknowledged by her or Amgen, where she is working on Phase his mentor and presented with her or Former Chief Clinical Scholar Dr. I studies in the areas of osteoporosis and his degree. Dr. Coller, the director of the Edgar Charles’ interest in Hepatitis C diabetes. Center for Clinical and Translational virus (HCV) began during his NYU Science (CCTS), congratulated the first fellowship where he was responsible for Before joining the Clinical Scholars class of scholars on their achievements the care of many patients suffering from Program, Dr. Lisa Neff completed and their commitment to use the full HIV/HCV co-infection. His interests in fellowships in Endocrinology and power of the scientific method to improve viral pathogenesis and immunology led Clinical Nutrition at Tufts-New England human health and alleviate suffering him to the Laboratory of Virology and Medical Center and the USDA Human from disease. Dr. Sarah Schlesinger, Infectious Disease under the direction of Nutrition Research Center on Aging at co-director of the Clinical Scholars Dr. Charles Rice and Dr. Lynn Dustin. Tufts University. In Dr. Jan Breslow’s Program within the CCTS stated, “It Dr. Charles’ research is focused on the Laboratory of Biochemical Genetics and has been inspiring to watch our ideas mechanisms by which HCV infection Metabolism, Dr. Neff’s research focused for the Clinical Scholars program grow leads to B cell dysregulation. Dr. Charles on identifying effective nutritional into reality. I am most impressed by the received a prestigious NIH K08 award interventions for obesity and the talent and commitment of our graduates. from the National Institute of Allergy and metabolic syndrome. She successfully Each of them is a remarkable young Infectious Disease (NIAID) to support completed both a randomized metabolic physician/scientist with an important his research under the mentorship of diet study and a longitudinal weight contribution to make. I believe that Drs. Rice and Dustin. He will continue management intervention study the Clinical Scholars Program has his research on HCV with a view toward during her time in the program. The given them the tools they need to move the development of novel therapies. preliminary data from her metabolic diet forward and make a difference.” study suggests that clinically significant Shortly after she began her Endocrinology improvements in insulin resistance, Dr. Marina Caskey trained in Infectious Fellowship at Weill Cornell Medical inflammation, and other obesity-related Diseases at Weill Cornell Medical Center, College, Dr. Allegra Grossman developed derangements can be achieved through and after completing her fellowship, a strong interest in diabetes and dietary changes, even in the absence of joined the laboratory of Dr. Ralph metabolism. As a result, she was eager to weight loss. Plans are being made to Steinman. As a Clinical Scholar, Dr. join Dr. Markus Stoffel’s Laboratory of launch a new fully-powered clinical Caskey studied the immune responses Metabolic Diseases to study fundamental trial building on these results. In the elicited by a novel HIV-1 vaccine in aspects of diabetes. As a Clinical Scholar, fall of 2009, Dr. Neff will join the which a monoclonal antibody delivered Dr. Grossman conducted studies on the Comprehensive Center on Obesity at the antigen to the dendritic cells for relation of obesity with frequency of Northwestern University and will serve processing and immune stimulation. meals and expression of the important as an Assistant Professor in the Division She has also worked to bring this novel transcription factor FOXA2 in adipose of Endocrinology. She will continue to candidate HIV vaccine into Phase I tissue of human subjects with obesity/ study and treat individuals with obesity clinical development at the CCTS. insulin resistance. Additionally, she and related metabolic derangements. Upon completing the Clinical Scholars developed her own study to investigate

3 Integrated Research Information System (iRIS) Update By Donna Brassil The Center for Clinical and Translational Protocol Submission Sign-Off Request the now paperless Conflict of Interest Science (CCTS) utilizes the electronic (COI) form. Both of these are essential Before a study is officially accepted Integrated Research Information System components of the IRB submission by iRIS, Key Study Personnel will (iRIS), which offers many components process. If any member of the study receive an email from ruhstudies@ that are advantageous to the investigators, team does not sign-off on the study, mail.rockefeller.edu with a subject line coordinators, other research staff, the study will not be submitted to the stating: Protocol Submission Sign-Off Institutional Review Board (IRB) respective review boards. Request. Completing the sign-off is an members, and the members of Advisory important step in the process and needs One great advantage of the electronic Committee for Clinical and Translational to be completed before the study enters submission system is that each KSP can Science (ACCTS). This issue will highlight the review process. This ensures that all view all study submission documents the advantages of being designated one of study personnel have seen and support and sign off on the study regardless of the Key Study Personnel (KSP) in iRIS. the pending protocol. Personnel should where they are located as long as they What are KSP? log onto the iRIS Submission System have internet access and have logged at https://clinfo10.rockefeller.edu/. The into the University’s Virtual Private For research studies, Key Study Personnel user ID and password are identical to Network (VPN). (KSP) are Rockefeller University those used for the Rockefeller University faculty and staff named on a clinical email system. After logging into iRIS, If you have any questions about iRIS, feel free to contact Ross Gillman (212) 327-8930; research study. They may be a Principal KSP can view all submitted documents Investigator, co-Investigator, Nurse Ummey Johra at (212) 327-7877; or Donna related to the study. At the same time Brassil at (212) 327-7886. Practitioner, Coordinator, Bionutritionist, while in iRIS, KSP are asked to complete Lab Technician, etc. Center Achieves Community Engagement Milestones By Rhonda Kost, MD

In April 2009, Dr. Kenneth Olden, at the Harvard School of Public Health. Dr. Daniel Blumenthal, Professor and Founding and Acting Dean of the Dr. Olden has defined the goal of CUNY’s Chair of the Department of Community new City University of School of Public Health as “to train Health and Preventive Medicine at (CUNY) School of Public Health, interdisciplinary urban public health Morehouse School of Medicine served sited at Hunter College, joined the researchers and practitioners capable as a consultant to CCTS under the Advisory Committee on Community of working across all levels of analysis, auspices of a Duke University CTSA Engagement and Recruitment (ACCER) disciplines, and social sectors -- such as consortium-wide project termed the as an advisor to, and collaborator health, education, the environment, and Community Engagement Consultative with, the Rockefeller University Center criminal justice -- to address complex Service (CECS). Dr. Blumenthal has for Clinical and Translational Science urban public health problems.” served as a consultant to the World (CCTS). ACCER, a subcommittee of Health Organization in Geneva; a Dr. Olden and the ACCER Board, the Advisory Committee for Clinical VISTA Volunteer physician in Lee (consisting of Mr. Joseph Bonner, Dr. and Translational Science (ACCTS), County, Arkansas; as an Epidemic Barry Coller, Dr. Peter Holt, Dr. Bonnie is responsible for the implementation Intelligence Service Officer with the Kaiser, Dr. Rhonda Kost, Ms. Maija of the Community Engagement Key Centers for Disease Control in Atlanta; Neville, and Dr. Jonathan Tobin), Function at Rockefeller. Dr. Olden and as a medical epidemiologist have begun developing plans to foster brings a wide breadth and depth of with the World Health Organization interdisciplinary collaborations that experience in science, public policy, and Smallpox Eradication Program in India partner traditional population-focused community engagement to his leadership and Somalia. Dr. Blumenthal visited public health concerns, including of the new School of Public Health the Rockefeller campus on May 20, health disparities, with biological and and to Rockefeller. Dr. Olden served 2009 and, in addition to providing mechanistically focused research on the as Director of the National Institute his consultation, delivered a Clinical molecular basis of stress and its impact of Environmental Health Sciences and Research Seminar, entitled: “Community on health risk. Coupling these disciplines the National Toxicology Program from Partnerships for Translational Research.” holds great potential for synergy in 1991-2005, where he was recognized The Rockefeller team described the addressing public health challenges internationally for his leadership. More current program to Dr. Blumenthal and accelerating the dissemination of recently, he was a Yerby Visiting Professor research findings into practice. (continued on page 5)

4 Center Successfully Applies for Four American Recovery and Reinvestment Act of 2009 (ARRA) Administrative Supplements By Maija Neville

On March 19, 2009 the National Center for Research Resources (NCCR) issued a request for Administrative Supplements to institutions and organizations with validate a methodology by comparing 3. Administrative Supplement to Advance active NIH Research Grants. This request its results to those from traditional Translational (T1 & T2) Research, Knut was based on the American Recovery approaches; (2) to conduct a proof of Wittkowski, secondary PI. To Advance and Reinvestment Act of 2009 (ARRA), principle analysis to explore a recent Translational (T1 & T2) Research by which was signed into law on February finding from ongoing research under increasing accuracy and accelerating 17, 2009 with the goal of promoting job the parent CTSA award which suggests analyses and dissemination of results, creation and economic development, that genetic factors may determine why two critical enhancements with long- along with accelerating the pace and psoriasis affects primarily the skin in some term implications for the use of the achievement of scientific research. patients, while others develop psoriatic Rockefeller-developed programs µStat Supplements could be submitted under arthritis; and (3) to accelerate sharing of and WISDOM as resources for clinical an NIH CTSA parent award. The goal of technology through rapid dissemination and translational research will be made. each supplement was to advance either of the results, Web-based documentation (1) CCTS will partner with industry to the NCRR Pilot Project Mechanism, of the analyses as case studies for the use move WISDOM another step towards the CTSA Consortium Strategic Goals, of the novel technology and development becoming a comprehensive support Collaborative Community Engagement of training material in collaboration with system for clinical and translational Research, Science Education and neighboring CTSA institutions in the scientists by making the meta database Dissemination, Collaborative and area. already used for the REDCap link a Basic and Translational Research, or resource shared with a graphical user 2. Administrative Supplement to Advance Research Workforce Development and interface to assist and provide help Translational (T1 & T2) Research, Agata Dissemination. Of the Supplements with specifying statistical analyses to be Smogorzewksa, secondary PI. Using the submitted by the Rockefeller University performed on the µStat Web server. (2) A Bleeding History Phenotyping System as Center for Clinical and Translational full time software engineer will be hired a prototype of a comprehensive patient Science (CCTS), four were recommended to provide technical assistance to clinical phenotyping instrument, this submission for funding on July 15, 2009. If awarded and translational researchers while proposed the creation of a comprehensive, at the requested budgets, they will result enhancing the capacity, stability, and ontology-driven phenotyping system and in $2,234,770 in additional total funding functionality of the grid, in general, and database for Fanconi anemia (FA). Work over two years. Five new staff members automating the iterative resubmission of stemming from this proposal will create will be hired to conduct the studies. A interim results as the number of factors a uniform phenotyping ontology based brief description of the supplements analyzed increases. After the 2-year on a comprehensive Fanconi Anemia recommended for funding are provided period, WISDOM will facilitate clinical Phenotyping Questionnaire (FAPQ) below. and translational research as a coherent that will be designed and peer-reviewed user interface with intelligent, knowledge- 1. Administrative Supplement for by experts in the field. Information will based help for both REDCap as a data Enhancing NCRR Pilot Project be used to generate a Fanconi anemia entry system and µ-stat as an innovative Mechanism, Knut Wittkowski, secondary phenotyping database (FAPD), which will statistics server. To accelerate further PI. This Pilot Project aims at using the be accessible to physicians and researchers development, it will have been ported NCBI CASP database of Genotypes and worldwide through a secure Web-based to the industry standard Java and have Phenotypes (dbGAP): (1) to empirically interface. (continued on page 9)

Center Achieves Community Engagement Milestones (continued from page 4) through a series of meetings with faculty, around which to build the consultation. be “highly likely” to continue to be ACCER members, Clinical Scholars, and Rockefeller selected: 1) how to design successful in achieving our stated goals, collaborators, including Dr. Kenneth flexible projects that incorporate the and in executing the plan of action. Olden and Dr. Jonathan Tobin, President community, and 2) building long term He noted that the CCTS’s “strategic and CEO of Clinical Directors Network, relationships with community partners. alliances with partners that have deep a community-based research network. connections to the community” was After reviewing all the materials and From a list of 30 practices endorsed by an extremely appropriate approach for conducting his analysis, Dr. Blumenthal the CECS workgroup, Rockefeller was Rockefeller. judged the Rockefeller program to asked to focus on 1-2 best practices

5 Meet the Scholar: Swaroop Pendyala, M.D. By Jennifer Spada Dr. Swaroop Pendyala received his medical degree from Christian Medical College, India in 1997. After completing his degree he spent time working as an acute care physician internationally, first in England and then in Jamaica. He began his residency in Internal Medicine at the University of Texas in Galveston, which he completed at St. Luke’s-Roosevelt Hospital of Columbia University, New York in 2007.

Dr. Pendyala initially became interested in medical research while working under Dr. William Mitch during his first year of residency at the University of Texas. Under the guidance of Dr. Mitch, his research involved understanding the role of phosphatidyl 3-kinase (PI3K) as the major signaling pathway in controlling contribute to the increased risk of colon University, Dr. Pendyala stated “The muscle mass in different catabolic cancer with obesity.” Clinical Scholars program has been medical conditions. After moving to amazing, especially in helping me to New York for his third year of residency, Dr. Pendyala is currently working on understand and learn the process of he worked on projects to understand two studies at Rockefeller University conducting translational research. the role of bone marrow-derived cells in Hospital. The first, which was funded by a Going through the rigor of good clinical the pathogenesis of chronic pancreatitis pilot grant from the CTSA, is investigating practice and attending Institutional and pancreatic cancer with Dr. Timothy the presence of inflammation in the Review Board meetings has given me Wang at Columbia University. During colorectal epithelium of obese women the confidence and training to conduct his time at Columbia he met Dr. Peter and the effects of weight loss by dietary translational research. Dr. Barry Coller Holt, a Senior Research Associate in intervention on the inflammation. Thus, has been a great source of knowledge the Laboratory of Biochemical Genetics this study is testing whether the increased and support in understanding the and Metabolism at the Rockefeller inflammation associated with obesity process of becoming a successful University, who introduced him to the provides a direct link to increased risk researcher. Additionally, Drs. Holt and Clinical Scholars program. At that time of malignancy. Preliminary results have Breslow have been remarkable mentors, he wanted to join a research lab to gain shown improvement in inflammatory as they have experience as preeminent experience in translational research in markers in the colorectal mucosa after translational researchers.” gastroenterology. weight loss by dietary intervention. His second study is exploring the ways When asked about his future, Dr. In 2007, Dr. Pendyala was accepted that a “Western style” diet increases the Pendyala said, “I will be starting into Dr. Jan Breslow’s Laboratory of risk of colorectal carcinogenesis. “The my gastroenterology fellowship at Biochemical Genetics and Metabolism Western style diet is a major risk factor Columbia University’s St. Luke’s- as a Clinical Scholar under the for colorectal carcinogenesis, but there Roosevelt Hospital. I will be applying for mentorship of Drs. Breslow and Holt is very limited information on how it further grant support for larger clinical to investigate the mechanisms involved promotes carcinogenesis; this study is studies based on the initial information in increased risk of colorectal cancer in aimed at trying to gain insights into the obtained from the studies conducted here obese individuals. Dr. Pendyala stated, earliest changes in different molecular at Rockefeller University Hospital. My “Forty -two percent of all colon cancers pathways in the colorectal epithelium. career plan is to focus on understanding are diagnosed in obese individuals. With We hope that by understanding these the molecular mechanisms of sporadic a quarter of the adults in the United early changes we will be able to direct colorectal cancer in normal and obese States being obese and nearly two thirds future studies to preventive strategies individuals by conducting translational of the adults being overweight the that target these specific pathways.” research studies. I believe that my training incidence of these cancers in the future in the Clinical Scholars program has will undoubtedly increase. We still do When asked to discuss his experience provided me with the skills to achieve not understand the mechanisms that as a Clinical Scholar at Rockefeller academic success!”

6 ~ Rockefeller University Hospital Centennial Celebration ~ Discoveries Advancing Medicine

As part of the centennial celebration of the Rockefeller University Hospital, Dr. Elizabeth Hanson has led a project to create a permanent record of more than 100 medical advances that have come from Rockefeller faculty. To share this wealth of exciting information, we will highlight one of these Discoveries Advancing Medicine in each future e-Newsletter. We start by featuring the remarkable translational research contribution by Louise Pearce and her colleagues.

Barry Coller, MD

Louise Pearce and the First Drug for African Sleeping Sickness By Elizabeth Hanson, PhD Tryparsimide was derived from arsenic. honorary degrees, Pearce also served In 1909 , in Germany, had as president of the Women’s Medical developed an arsenic-derived drug called College of Pennsylvania from 1946 to Salvarsan, which was the first effective 1951. treatment for syphilis. Since Ehrlich had also found that related arsenic compounds could kill trypanosomes, , director of the Rockefeller Selected Publications Institute, directed two chemists, Walter Jacobs and , to Pearce L. Tryparsamide treatment of African Sleeping Sickness. Science, 1925, 61:90-92 develop new arsenic formulations for treating trypanosomiasis in humans. Pearce L and Rivers TM. Effect of a Flexner enlisted two members of his filterable virus (Virus III) on the growth and own laboratory, Wade Hampton Brown malignancy of a transplantable neoplasm of the rabbit. J Exp Med, 1927, 46: 81-99 and Louise Pearce, to study the disease, http://www.jem.org/cgi/reprint/46/1/81 and test the experimental drugs, in animal models. When the four scientists Pearce L. The Treatment of Human Trypanosomiasis with Tryparsamide. A Critical determined that Tryparsamide was the Review. Monograph no. 23. New York: most promising drug, Pearce traveled to Rockefeller Institute for Medical Research, Africa to conduct human trials. 1930 In 1920 Louise Pearce (1885-1959) traveled to the Belgian Congo (now Louise Pearce received the AB from Casey AE, Rosahn PD, and Pearce L. The association of blood cell factors with the Democratic Republic of the Congo) in 1907 and the MD from the transplantability of the Brown-Pearce tumor. to field test a new drug against Cancer Res, 1942, 2: 284-289 trypanosomiasis, or African sleeping School of Medicine in 1912. That sickness. This fatal disease, caused by a year she took a research position at blood parasite, was epidemic. Working the Rockefeller Institute under Simon Further Reading in a clinic in the country’s capital, Flexner, the Institute’s director, and she was promoted to associate member in Bediner E. Louise Pearce: A “magic bullet” for Pearce developed a protocol for testing African Sleeping Sickness. Hospital Practice, 1923. Pearce remained at Rockefeller the the drug’s safety, effectiveness, and 1992, 27: 207-221 optimum dosage. Called Tryparsamide, rest of her career. Much of her work was Corner, GW. A History of the Rockefeller the new treatment cured about 80 devoted to developing animal models for the study of human cancers. Of Institute, 1901-1953. (New York: Rockefeller percent of patients, although high doses Institute Press, 1964), 144-148 given for severe cases had the side effect the researchers involved in developing Grinstein LS, Biermann CA and Rose RK, of partial or complete loss of vision. Tryparsamide, Pearce was the most celebrated: she was awarded the Belgian eds. Women in the Biological Sciences: A This achievement received immediate Bibliographic Sourcebook (Westport, CT: Order of the Crown in 1921 and the international recognition. For decades Greenwood Press), 1997, 384-390 Tryparsamide remained the standard King Leopold II Prize in 1953. The treatment for trypanosomiasis. recipient of many additional awards and

7 The Clinical Research Support Office Post-Approval Audit Program PART II: Documenting Enrollment, and a New and Improved Informed Consent Template By Rhonda G. Kost, MD

In the past three years, no audit findings of completion by the participant at the There can be subtleties to the Enrollment clinical studies at Rockefeller University time of the study visit, preferably before Note. It may not be possible to satisfy have identified significant risks to the investigator or participant has left all four elements of the Enrollment participant safety, or serious violations of the clinic. This insures that the errors documentation listed above on the subjects’ rights. The audits did, however, are identified when the signatories are same day. Regarding eligibility, for identify instances of omissions of tests or still available to correct their entries in instance, if informed consent is signed visits, and incomplete documentation. real time. The investigator’s signature at a given visit, but not all inclusion/ These lapses can be addressed by should be the final sign-off of the form exclusion criteria can be satisfied until process improvement and increased as checked and complete. test results return at a subsequent time, attention to detail. In this article, we will then the documentation of Enrollment review the required documentation of New Informed Consent and HIPAA would consist of two notes, one written participant enrollment, which includes a Templates to document items 2-4 above, and fully executed Informed Consent Form, In response to our audit findings that a subsequent note written to verify completed HIPAA form, and a well- participants are asked to provide that inclusion/exclusion criteria were designed Enrollment Note. duplicate contact information several satisfied. In documenting that all of the participant’s questions were answered, Informed Consent and HIPAA forms times during the enrollment process, including when completing the HIPAA it is recommended that a summary Among the most common audit findings form, we consulted the Office of General statement of the nature of the questions around the process of enrollment are Counsel and IRB to review whether the the participant asked be included (e.g., irregularities in the completion of the contact information section of the HIPAA “the participant requested and was given Informed Consent Form. A properly form was in fact required. As a result of clarification about the visit schedule completed Informed Consent Form is these reviews, the contact information and schedule of compensation.”) It is executed with: 1) the correct, current field has been eliminated from the not, however, necessary to document IRB-approved version of the form as HIPPA form. Similarly, in response to every question. It is best to avoid listed on-line; 2) all sections completed, audit findings, and in collaboration with judgments about the participant’s including the Sample-Storage and the Office of General Counsel and IRB, comprehension such as “the participant Future-Use section (more below); 3) we have rewritten the Sample-Storage now understands,” unless a formal signatures on the correct line from the and Future-Use section of the Informed assessment of comprehension was made. participant him/herself (not a spouse or Consent form template, making it much Rather a statement of fact, such as “the friend, even if the spouse or friend has shorter and simpler. Both of these new participant stated that the explanation better handwriting), except where a legal forms should be available for use for was clear.” guardian, parent, or proxy is indicated; November or December submissions to The signatures on the Informed Consent 4) current date recorded at the time of the the IRB. must always include the date, entered by signing, on the correct line, by the person the person signing. In establishing clearly signing the document; 5) any corrections Enrollment Notes that Informed Consent was signed before made by the person who made the Documentation of eligibility and any study procedures began, for instance original entry, with a single line through informed consent, both of which are when study procedures begin on the same the original entry, dated, and with initials required by Good Clinical Practices day that Informed Consent is signed, the of the corrector next to the correction. (GCP) and federal regulations (46 record should include notation of the Finally, no ad lib additions or deletions CFR 46.117 and 21 CFR 50.27), is time that the Informed Consent Form may be made to the content of an IRB- captured by Rockefeller University was signed, and precede the time that approved consent form; for example, no IRB Procedures (Section 6.1) in the any procedures are documented to have circling, cross-outs, underlining or write- requirement for an Enrollment Note. begun. Finally, the regulations requires in words for emphasis should appear on The Enrollment Note should document: that a copy of the ICF be given to the the form as they invalidate the form as 1) the eligibility of the participant for participant, not just offered, even if the IRB-approved. Among HIPAA forms, the protocol, 2) that the subject had a participant declines it. You can explain the most common lapse is omission of chance to ask questions and have them to the participant that they are required the contact information section. answered prior to signing the ICF, 3) to accept it, but not keep it. One effective way assure correct that the ICF was signed prior to the An Enrollment Note Template/ documentation is to assign a research subject undergoing any study-related Checklist can structure and facilitate the team member the task of thoroughly procedures, and 4) that a copy of the documentation of each of the required reviewing the forms for correct signed Informed Consent Form (ICF) was given to the subject. (continued on page 9)

8 Center Successfully Applies for Four American Recovery and Reinvestment Act of 2009 (ARRA) Administrative Supplements (continued from page 5) an innovative and easily expandable for DNA, RNA, and protein sequencing full advantage of knowing what it takes help system to facilitate training and is generating vast amounts of data from to draw valid scientific conclusions dissemination. scientific experiments. Therefore, it is of from such data. This course will look great value to the researchers responsible at the subcategories of bioinformatics 4. Administrative Supplement for for such experiments to understand the including genomics, protein structure Research Workforce Development tools and techniques that are available to and interaction networks, metabolomics, and Dissemination, Edward Barbour, analyze this vital data. As in many areas natural language processing, and secondary PI. This supplement proposes of rapidly advancing technology, many simulation using complex systems. The to create a comprehensive course in educational programs are not able to course will also expose the researcher the area of Applied Bioinformatics keep up with the advanced pace of this to currently available bioinformatics for the further education of clinical educational need. This submission will fill tools including open source and leading researchers. The field of bioinformatics, that gap by creating a Web-based course third party tools, as well as the low level which applies information technology to that will contain numerous examples components used to build such tools. molecular biology data, is being elevated and exercises, giving the researcher the to a prominent role as newer equipment

The Clinical Research Support Office Post-Approval Audit Program PART II: Documenting Enrollment, and a New and Improved Informed Consent Template (continued from page 8) elements. During the conduct of audits of available to help research teams achieve system can be a helpful resource as well. active studies, auditors routinely verify compliance, and are always available to Taking advantage of the support of that the elements of an Enrollment Note answer any questions or help solve any the Facilitation Office, iRIS workflow, has been properly documented for every problems that arise for investigators and and post-audit recommendations from participant. The Facilitation Office is their staff. the CRSO, research teams can develop available to help investigators construct routine practices that make regulatory Workflow, Tools, and Habits such templates before starting the study. compliance a straightforward and If deficiencies in the Enrollment Note Coordinators from the Facilitation automatic part of daily study conduct. are detected on audit, the auditor will office are available to help research staff assist the investigator in amending the members develop tools to ensure the record as part of a Corrective Plan of completion of protocol-related activities In the next issue: Documenting, Reporting, Action. As always, the Clinical Research and appropriate scheduling of study and Avoiding Protocol Deviations and Support Office (CRSO) (x7709) and visits and procedures; worksheets Violations Facilitation staff members (x7886) are created through the iRIS electronic

Rockefeller University Hospital Summer, 2009 Photo Credit: Karen Smith 9