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Public Workshop: Safety Assessment for Investigational New Drug Safety Reporting

1777 F St NW Conference Center • Washington, DC

March 8, 2018

Biographies

Robert Baker Robert Baker is a VP of Eli Lilly and Company and leads several groups within its Medicines Development Unit: -Global Patient Safety, overseeing Pharmacovigilance, Benefit-Risk management, and product safety strategy and assessment. -Clinical Development Design Hub. This newly created organization will serve as a center of expertise consulting on all clinical program designs and with assistance from molecule teams will produce all clinical protocols and clinical trial packages. -Clinical Pharmacology Medical/Design Group. Robert supervises the physicians and design teams within Clinical Pharmacology, responsible for exploratory medicine, SAD/MAD trials, and biopharmacology studies. Robert has been at Lilly for 18 years in various roles across Drug Discovery, Drug Safety, and Medical Affairs. Prior to joining Lilly he was an Academic Psychiatrist studying schizophrenia and substance abuse. Robert completed medical school at Northwestern University and psychiatry training at the University of Pittsburgh.

Amit Bhattacharyya Amit Bhattacharyya, PhD, is the Vice President of Biometrics at ACI Clinical. ACI Clinical, based in Bala Cynwyd, PA, is a niche service provider, specializing in oversight and guidance of clinical programs, data and endpoints through independently managed Safety Expert Committees, including full-service Endpoint Adjudication Committees, Data (Safety) Monitoring Committees, and Safety Assessment Committees. Dr. Bhattacharyya is a thought leader in Drug Safety area, and currently serves in leadership roles for American Statistical Association (ASA) Biopharmaceutical Section’s Safety Working group. Prior to joining ACI, he spent more than two decades at GSK in various global statistical leadership roles in discovery, preclinical safety, clinical development and Real-World Evidence research. Amit is also well known in the statistics community for his senior leadership roles in national and international statistics societies over the last 15 years. He has presented in many conferences on statistical, safety and statistical leadership issues. Dr. Bhattacharyya earned his PhD in Statistics from the University of Maryland.

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Erin Bohula

Erin Bohula, MD, DPhil is an Associate Physician in Cardiovascular Medicine at Brigham and Women's Hospital, an Instructor of Medicine at Harvard Medical School, and an Investigator at the TIMI Study Group. Dr. Bohula earned her Doctor of Philosophy (D.Phil.) in Molecular Biology from Oxford University on a Rhodes Scholarship and her medical degree (M.D.) from Harvard Medical School. She completed her internal medicine residency and fellowships in cardiovascular medicine and critical care medicine at Brigham and Women's Hospital. She is board certified in internal medicine, cardiology, and critical care medicine. In her role as a TIMI Study Group Investigator, Dr. Bohula studies pharmacologic interventions for

atherosclerotic cardiovascular disease. As a cardiac intensivist and researcher, she is interested in innovative therapies and devices for critically-ill cardiovascular patients. In addition to her scientific and trial responsibilities, Dr. Bohula is an active member of the clinical staff at Brigham and Women's hospital and attends in the Cardiology Critical Care Unit and inpatient General Cardiology Service.

Anand P. Chokkalingam Anand is Director of Epidemiology at Gilead Sciences, where he heads the Epidemiology unit for Gilead’s liver disease portfolio. His team leads post-authorization/post-marketing studies around the globe and applies pharmaco-epidemiology methods to real world data. Anand is also an Associate Adjunct Professor of Epidemiology at the UC Berkeley School of Public Health. He came to Gilead in 2013 after eight years on faculty at UC Berkeley, and has previously worked for several biotech and molecular diagnostics companies including Syva/Syntex, Celera, Tethys, and Roche Molecular Systems. He has a B.A. in Biochemistry from UC Berkeley and both an M.S. in Preventive Medicine and a Ph.D. in Epidemiology from the University of Maryland Baltimore, and he completed a post-doctoral fellowship in Cancer Epidemiology at the U.S. National Cancer Institute’s Division of Cancer Epidemiology and Genetics.

Jacqueline Corrigan-Curay Jacqueline Corrigan-Curay, J.D., M.D., serves as Director of CDER’s Office of Medical Policy (OMP). She leads the development, coordination, and implementation of medical policy programs and strategic initiatives. She works collaboratively with other CDER program areas, FDA centers, and stakeholders on enhancing policies to improve drug development and regulatory review processes. OMP is comprised of the Office of Prescription Drug Promotion (OPDP) and the Office of Medical Policy Initiatives (OMPI). OPDP oversees the regulation of prescription drug promotion and advertising. OMPI provides oversight and direction for new and ongoing policy initiatives in broad-based medical and clinical policy areas. Prior to joining FDA, she served as supervisory medical officer with the Immediate Office of the Director, National Heart, Lung

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and Blood Institute (NHLBI), at National Institute of Health’s (NIH) where she focused on developing policies and procedures to enhance the clinical trial enterprise. She also served as the Director of the Office of Biotechnology Activities (OBA), Office of Science Policy at NIH, where she was executive secretary of the NIH Recombinant DNA Advisory Committee. She has held positions as an attending physician with the VA Medical Center, a policy analyst with the Congressional Office of Technology Assessment, and a practicing attorney in Washington, D.C. Dr. Corrigan-Curay earned her law degree from Harvard Law School, her medical degree from University of Maryland School of Medicine, and a bachelor’s degree in history of science from Harvard/Radcliffe College in Cambridge, MA. She completed her training in internal medicine at Georgetown University Medical Center, where she also served as a clinical assistant professor of medicine. She continues to practice internal medicine part-time at the Veterans Affairs Medical Center in Washington, D.C.

Gerald Dal Pan

Gerald J. Dal Pan, MD, MHS, currently serves as the Director of the Office of Surveillance and Epidemiology in FDA’s Center for Drug Evaluation and Research, where since 2005 he has been responsible for the Center’s programs in adverse event surveillance and analysis, pharmacoepidemiology, risk management, and medication error prevention. In this capacity, he is involved in both the premarket and postmarket regulation of drugs and therapeutic biologics, and in the implementation of the drug safety provisions of the Food and Drug Administration Amendments Act and other initiatives. He is a member of the World Health Organization Advisory Committee on the Safety of Medicinal Products, and has served on working groups of the Council of International Organization of Medical Sciences (CIOMS) and the International Conference on Harmonisation (ICH). He received his MD from Columbia University College of Physicians and Surgeons and his Master of Health Science in Clinical Epidemiology from the Johns Hopkins University School of Hygiene and Public Health. He completed residency training in Internal Medicine at the Hospital of the University of Pennsylvania and in Neurology at the Johns Hopkins Hospital. He is board certified in both Internal Medicine and Neurology. He joined FDA in 2000 as a medical reviewer in the Center’s Office of New Drugs. Before working at FDA, he was a full-time faculty member in the Department of Neurology at Johns Hopkins and worked in the pharmaceutical industry.

Adrian Dana Dr Adrian Dana is the VP of Global Patient Safety and Risk Management at Alnylam, a leader in the development of RNAi therapeutics. In this role, she is building an innovative safety organization to support the development of this new therapeutic class. Her past positions include VP, Safety Science Oncology at Genentech/Roche, and 10 years at Merck in Clinical Safety and Risk Management. Her experience includes multiple therapeutic areas encompassing vaccines, infectious diseases and oncology. During her time in industry she has contributedto the filings and ultimate approval for more than 9 new vaccines and drugs. Adrian is a pediatric infectious diseases specialist and was in academic clinical practice prior to joining industry.

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Gregory Daniel

Dr. Gregory Daniel, PhD, MPH, is the Deputy Director of the Duke-Robert J. Margolis, MD Center for Health Policy and a Clinical Professor in Duke's Fuqua School of Business. Dr. Daniel directs the DC-based office of the Center and leads the Center's pharmaceutical and medical device policy portfolio, which includes developing policy and data strategies for improving development and access to innovative pharmaceutical and medical device technologies. This includes post-market evidence development to support increased value, improving regulatory science and drug development tools, optimizing biomedical innovation, and supporting drug and device value-based payment reform. Dr. Daniel is also Adjunct Associate Professor in the Division of Pharmaceutical Outcomes and Policy at the

UNC Eshelman School of Pharmacy. Previously, he was Managing Director for Evidence Development & Biomedical Innovation in the Center for Health Policy and Fellow in Economic Studies at the Brookings Institution and Vice President, Government and Academic Research at HealthCore (an Anthem, Inc. company). In addition to health and pharmaceutical policy, Dr. Daniel’s research expertise includes real world evidence (RWE) development utilizing electronic health data in the areas of health outcomes and pharmacoeconomics, comparative effectiveness, and drug safety and pharmacoepidemiology. Dr. Daniel received a PhD in pharmaceutical economics, policy and outcomes from the University of Arizona, as well as an MPH, MS, and BS in Pharmacy all from The Ohio State University.

David L. DeMets David L. DeMets, PhD is currently the Emeritus Max Halperin Professor of Biostatistics and former Chair of the Department of Biostatistics and Medical Informatics at the University of Wisconsin – Madison He has co-authored numerous papers on statistical methods and four texts on clinical trials, two specifically on data monitoring. He has served on many NIH and industry-sponsored data monitoring committees for clinical trials in diverse disciplines as well as a FDA panel member. He served on the Board of Directors of the American Statistical Association, as well as having been President of the Society for Clinical Trials and the Eastern North American Region (ENAR) of the Biometric Society. In addition, he was Elected Fellow of the International Statistics Institute, the American Statistical Association, the Association for the Advancement of Science, the Society for Clinical Trials and the American Medical Informatics Association. In 2013, he was elected as a member of the Institute of Medicine/National Academy of Medicine.

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Thomas R. Fleming Thomas R. Fleming, PhD, is Professor and former Chair of the Department of Biostatistics at the University of Washington in Seattle, Member of the Fred Hutchinson Cancer Research Center, and the former Director of the Statistical Center for HIV/AIDS Prevention Trial Network, NIAID. Dr. Fleming received his BA in 1972 from the University of St. Thomas and his MA in 1974 and PhD in 1976 from the University of Maryland, College Park. Dr Fleming has authored or coauthored several books and more than 250 research articles in peer-reviewed journals, many regarding the development of state of the art methods for the design, conduct and analysis of clinical trials, and many others reporting the results of landmark trials, including the 2011 publication in NEJM on prevention of transmission of HIV. This research, on which he was senior author, was recognized by Science Magazine to be the scientific “Breakthrough of the Year”. He has chaired or served on Data Monitoring Committees for more than 100 clinical trials. He is a Special Government Employee for the FDA, and for 30 years he has served as a regular member of several FDA Advisory Committees and as an invited voting member on more than 100 occasions. Dr Fleming has received numerous awards. He is recipient of the Outstanding Teaching Award, School of Public Health from the University of Washington, and the FDA Commissioner’s Special Citation Award for Extraordinary Contribution to the Agency. He is the 2007 Greenberg Lecturer at University of North Carolina, the 2009 Distinguished Lecturer at the School of Public Health at the University of Washington and, in 2011, the Ross Prentice Endowed Professor of Biostatistical Collaboration. In 2012, he was elected to membership in the Institute of Medicine of the National Academies.

Chris Granger

Christopher Granger is Professor of Medicine, Professor in the School of Nursing, and Director of the Cardiac Intensive Care Unit at Duke University. His primary research interests are in the coordination of large randomized clinical trials in heart disease and in implementation projects to apply optimal treatments. These projects include the Reperfusion of Acute MI in Carolina Emergency Departments (RACE) projects, North Carolina state-wide programs to improve care for acute myocardial infarction and cardiac arrest, and IMPACT-AF, a randomized trial to improve the care of atrial fibrillation in low and middle income countries. He is co-PI of the Sentinel IMPACT-AFib randomized trial testing patient education to improve anticoagulation care. He has co-authored more than 600 peer-reviewed

manuscripts and is a Thomson Reuters Highly Cited Researcher, reserved for the top 1% of cited researchers. He currently serves on three American College of Cardiology/ American Heart Association Guideline Committees. He received an honorary degree at the Carol Davila University in Bucharest Romania. He serves on editorial boards of the American Heart Journal, Journal of the American College of Cardiology and the European Heart Journal, among many others. He is co-author of the Fundamentals of Clinical Trials, a major textbook of clinical trials. He advises the FDA and serves the National Heart Lung and Blood Institute on a number of committees, including the Board of External Experts.

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Asif Haque Asif Haque, MD, is currently a Director in Patient Safety at Astra Zeneca Pharmaceuticals in the Cardio Vascular Renal & Metabolism TA. He is a pediatrician by training with a focus in Neonatalogy. He has experience working in multiple therapeutic areas and has led multiple global submissions as safety lead. He is also working at developing best practices for early detection, identification, management & mitigation of Drug Induced Liver Injury and best in practices for pharmacovigilance & clinical trial methodology.

Barbara Hendrickson

Barbara Hendrickson, MD is the Immunology Therapeutic Area Head in Pharmacovigilance and Patient Safety at AbbVie. She is a subspecialist in Pediatrics and Infectious Diseases and has over 14 years of pharmaceutical industry experience. Prior to joining industry, Dr. Hendrickson was in academic medicine for over 15 years, where she conducted clinical and basic laboratory research. At AbbVie, she has been co-leading the Safety Assessment Committee pilot project and the Safety Statistics Excellence Program initiatives.

Lisa LaVange

Lisa LaVange, PhD, is Professor and Associate Chair of the Department of Biostatistics in the Gillings School of Global Public Health at the University of North Carolina at Chapel Hill. She is also director of the department’s Collaborative Studies Coordinating Center (CSCC), overseeing faculty, staff, and students involved in large-scale clinical trials and epidemiological studies coordinated by the center. From 2011 to 2017, Dr. LaVange was director of the Office of Biostatistics in the United States Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER). There, she oversaw more than 200 statisticians and other staff members involved in the development and application of statistical methodology for drug regulation. She was a leader in developing and assessing the effectiveness and appropriateness of innovative statistical methods intended to accelerate the process from drug discovery to clinical trials to FDA approval and patients’ benefit, with a particular focus on rare diseases. Prior to her government and academic experience, she spent 16 years in non-profit research and 10 years in the pharmaceutical industry. Dr. LaVange is an elected fellow of the American Statistical Association (ASA) and is the 2018 ASA President.

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Mark Levenson

Mark Levenson is the Director of the Division of Biometrics 7 in the Office of Biostatistics/Office of Translational Sciences/Center for Drug Evaluation and Research of FDA. At FDA, he has been the primary reviewer or secondary reviewer on many major pre-market and post-market drug safety problems. He has contributed to the methodology of the application of meta-analysis and propensity score analysis to the regulatory setting. He is active in CDER’s efforts in the Sentinel Initiative, reducing prescription opioid abuse, and real-world evidence.

Elissa Malkin Elissa Malkin, DO, MPH is a Medical Director in Pharmacovigilance at BioMarin Pharmaceutical where she currently supports an investigational gene therapy candidate for hemophilia. She is a Family Practice trained physician who also completed a Preventive Medicine residency and a Masters in Public Health. Prior to transitioning into Pharmacovigilance at BioMarin, Elissa spent 15 years on the clinical side of drug development with a focus on global health, infectious disease and vaccine clinical trials at the National Institutes of Health, the PATH Malaria Vaccine Initiative and MedImmune.

Mary Nilsson Mary received a MS degree in statistics from Iowa State University in 1989. She has been employed at Lilly since 1989 and is currently a research advisor in the Safety Analytics group within the Statistical Sciences function. She consults with compound teams on safety analysis planning for Phase 2-3 studies and integrated submission documents. Her primary interests include analyses of adverse event data, analyses of laboratory data, statistical analysis plans, and collection and analysis of suicide-related events. Additionally, she co-leads a PhUSE Standard Analyses and Code Sharing Working Group involved with creating cross-industry recommendations for standard analyses and displays for data common across therapeutic areas with associated reusable code.

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Ajay Singh

Ajay Singh is a nephrologist by training and currently serves as a team leader in the Safety Evaluation and Risk Management group at GlaxoSmithKline.

Mat Soukup, Ph.D. Following his educational endeavors in statistics at the University of Minnesota-Morris and the University of Virginia, Mat joined FDA/CDER in September 2004. His first 6 years were spent reviewing dermatology and dental products before joining the Division of Biometrics 7 as Team Lead and later as Deputy Division Director. In these roles, Mat is involved in the quantitative assessment of safety covering a spectrum of statistical issues ranging from retrospective assessment of safety signals to prospective design of safety outcome trials.

Mary Ross Southworth Mary Ross Southworth is the Deputy Director for Safety in the Division of Cardiovascular and Renal Drug Products in the Center for Drug Evaluation and Research at FDA. Her responsibilities include managing safety activities in the division such as NDA safety review, safety labeling and communications, review of postmarketing safety studies and REMS. Previously, she was a safety reviewer in the Office of Surveillance and Epidemiology at FDA. She received a Bachelor of Pharmacy Degree from the Virginia Commonwealth University/Medical College of Virginia and went on to obtain a PharmD degree from the University of Toledo.

Peter P. Stein Peter P. Stein, M.D., Deputy Director, Office of New Drugs (OND), Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA). Peter earned his medical degree from University of Pennsylvania and trained at Yale-New Haven Hospital in internal medicine, and in endocrinology and metabolism. He was on faculty at Yale in the Section of Endocrinology and served as the associate program director for the Primary Care Residency Program. Subsequently, Peter was the section chief for endocrinology and the program director for internal medicine residency program at the Medical College of Georgia. Peter joined Bristol-Myers Squibb in 1999, subsequently

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working at Merck, Janssen, and finishing his career in industry at Merck as Vice-president for late-stage development in Diabetes and Endocrinology. During his industry career, Peter led development programs for several currently approved diabetes medications, and has worked on a wide range of programs from discovery through early and late clinical development. He is a clinical associate professor at the Robert Wood Johnson Medical School, where he maintained a practice in endocrinology for many years. Peter joined FDA in late 2016 as the Deputy Director, Office of New Drugs, CDER.

Ann Strauss Ann Strauss, MB BCh (Wits), DA (SA) is currently an Associate Vice President (AVP) and Therapeutic Area Lead Clinical Safety and Risk Management (CSRM) Merck Research Laboratories. Ann provides senior clinical safety and pharmacovigilance oversight to programs in the following areas: CV, Endocrine, Respiratory, Immunology, Neuroscience, and Women’s Health. She started her industry career in 1997 as a Training Associate at Glaxo Wellcome in South Africa and then joined MSD South Africa as a Medical Advisor in 1999. She moved to MRL in PA in 2001 as an Associate Director, Worldwide Product Safety and Epidemiology, and then progressed within the safety organization to Associate Director (2003) and Director (2006) in Clinical Risk Management and Safety Surveillance. In 2006, Ann moved to Wyeth in the role of Therapeutic Area Head and Senior Director, Medical Pharmacovigilance, initially supporting vaccines and anti-infectives and later neuroscience and GI products. Ann returned to Merck in January 2015 from her most recent position for the past five years as a Senior Director, Pharmacovigilance and Risk Management at Shire. Ann received her medical degree from the University of Witwatersrand in Johannesburg, South Africa, and her Postgraduate Diploma in Anaesthetics from the College of Medicine of South Africa.

Robert Temple Robert Temple has been Deputy Center Director for Clinical Science at FDA’s Center for Drug Evaluation and Research since 2009, participating in the direction of the Center’s operations. He is also Acting Deputy Director of the Office of Drug Evaluation I (ODE-I). ODE-I is responsible for the regulation of cardio-renal, neuropharmacologic, and psychopharmacologic drug products. Dr. Temple served as Director, Office of Medical Policy from 1999-2009. The Office of Medical Policy is responsible for regulation of promotion through the Office of Prescription Drug Products (formerly, Division of Drug Marketing, Advertising, and Communication) and for assessing quality of clinical trials. Dr. Temple has a long-standing interest in the design and conduct of clinical trials and has written extensively on this subject, especially on choice of control group in clinical trials, evaluation of active control and non-inferiority trials, trials to evaluate dose-response, and trials using “enrichment” designs.

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Bill Wang Dr. William (Bill) Wang is executive director, clinical safety statistics, in the department of Biostatistics and Research Decision Sciences (BARDS), Merck Research Laboratories. He has over 25 years of experience in the pharmaceutical industry, with expertise and research publications in statistical design, analysis, clinical data management and their technology enablement. During his 18-year tenure at Merck, he has supported regulatory filings in multiple therapeutic areas and established the BARDS Asia Pacific operation. Since 2012, he has served on the DIA’s Global Community Leadership Council (CLC). He was a recipient of the DIA global inspire/connector award in 2017. He is currently co-chairing an American Statistical Association (ASA) safety working group, and a deputy topics-leader in the ICH E17 working group on multi-regional clinical trials.

Janet Wittes

Janet Wittes, PhD is President of Statistics Collaborative, Inc. which she founded in 1990. Previously, she was Chief, Biostatistics Research Branch, National Heart, Lung, & Blood Institute (1983–89). Her 2006 monograph, “Statistical Monitoring of Clinical Trials – A Unified Approach” by Proschan, Lan, and Wittes, deals with sequential trials. Her research has focused on design of randomized clinical trials, capture recapture methods in epidemiology, and sample size recalculation. She has served on a variety of advisory committees and data monitoring committees for government (NHLBI, the VA, NEI, and NCI) and industry. For the FDA, she has been a regular member of the Circulatory Devices Advisory Panel and has served as

an ad hoc member of several other panels. Currently, she is a regular member of the Gene Therapy Advisory Committee. She was formerly Editor in Chief of Controlled Clinical Trials (1994-98).

Salim Yusuf Salim Yusuf, D.Phil, FRCPC is a Distinguished University Professor of Medicine at McMaster University, Director of the Population Health Research Institute, and is Chief Scientist at Hamilton Health Sciences. He holds a Heart and Stroke Foundation Research Chair, was a Senior Scientist of the Canadian Institutes of Health Research (1999-2004), and has received (among others) the Lifetime Research Achievement award of the Canadian Cardiovascular Society, the Paul Wood Silver Medal of the British Cardiac Society, the European Society of Cardiology gold medal, the American Heart Association Clinical Research Award, and over 35 other international and national awards for research, induction into the Royal Society of Canada and Canadian Medical Hall of Fame, and appointment as an Officer of the Order of Canada. He has led over 50 major international studies in over 100 countries and several of these have changed medical practice. He has published over 1000 articles in refereed journals, was the second most cited researcher in the world for 2011 and has the 17th highest H factor in history. He is the immediate Past President of the World Heart Federation, where he has

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been initiating an Emerging Leaders program in 100 countries with the aim of halving the CVD burden globally within a generation.

Funding for this conference was made possible in part by a cooperative agreement from the U.S. Food and Drug Administration Center for Drug Evaluation and Research. The views expressed in written conference materials or publications and by speakers and moderators do not

necessarily reflect the official policies of the Department of Health and Human Services nor does mention of trade names, commercial practices, or organizations imply endorsements by the U.S. Government.