Training Initiative

The Frontier Science ISC is hosting and participating in a training initiative for training Independent Data Monitoring Committee (IDMC) Members and Statistical Data Analysis Centers (SDAC).

Proposal

This initiative proposes to provide a process to train the current and next generation of clinical trialists involved in medical research or in biostatistics so they may serve effectively as members of an independent data monitoring committee (IDMC), whether government or industry sponsored, or provide statistical data analysis center (SDAC) support to these committees. Two parallel courses are planned, one tailored for potential IDMC members and a separate session for those wanting to provide statistical support as SDACs to the IDMCs. The SDACs may be separate standalone units or part of a larger randomized clinical trial (RCT) organization.

Background

Over the past five decades as the role of the RCT has appropriately evolved to become the gold standard for evaluation of new pharmaceuticals, devices, procedures and behavioral interventions, so has the role of the IDMC, also referred to as the Data & Safety Monitoring Board (DSMB). The IDMC/DSMB process, which was recommended by the Greenberg Report (ref), was implemented in the early primary and secondary prevention trials sponsored by the National Heart, Lung and Blood Institute (NHLBI). Accompanying the growth of the use of IDMCs in the past 25 years has been the increased use of an independent SDAC which provides interim reports for the IDMC. These reports allow the IDMC to fulfill its role to insure patient safety by monitoring the progress of the RCT as well as reviewing interim unblinded safety data frequently and interim unblinded efficacy data periodically. Based on review of the totality of the evidence, including the emerging unblinded data, the IDMC may recommend changes in the RCT or perhaps early termination if the data show evidence of harm or overwhelming evidence of benefit. This activity has been extensively described in the literature (refs EFD, DFF, DeMets/Penn paper, etc.) as well as the topic of recent meetings or forums (ref CTTI, DCRI Think Tank, ASA Biopharm Mtg).

The growth of usage of IDMCs has been substantial, perhaps in the several hundred or even thousands of trials registered in clinicaltrials.gov (ref Califf et al). Despite this enormous growth, the number of clinical and statistical scientists trained to be members of IDMCs and statistical groups with expertise and experience in providing SDAC-type support to IDMCs has lagged seriously behind. The Clinical Trial Transformation Initiative (CTTI) surveyed the state of activity and training by contacting current DMC members, RCT sponsors, SDAC groups and regulatory agencies regarding the level of participation in IDMCs and SDACs. While variations in practice were reported, there were also many commonalities (ref Calis, Bain et al). One outstanding result of their survey is that few of the current IDMC members had received any formal training for this crucial role. Even those with IDMC experience expressed the desire to have access to some formal training. The literature and forums mentioned above have all called for an organized training program to fill this growing gap. This conclusion is not new as this discussion has gone on for several years, yet no formal training program has emerged except for a couple of online presentations (ref NIH, Neaton-DeMets) and an occasional short course at professional meetings such as the Society for Clinical Trials or the American Heart Association annual meetings.

As part of the Clinical Trials Transformation Initiative (CTTI) DMC project, several of us who participated gave brief presentations of the attached material at the 2016 Society for Clinical Trial (SCT) annual meeting and the 2016 American Heart Association (AHA) annual meeting. A similar presentation was made at the American Statistical Association (ASA) BioPharm conference this past October of 2017 in Washington, DC. At that meeting on the state of IDMCs, participants in the audience supported the idea that there exists a gap between the supply of trained IDMC members and demand. We were challenged to lead the effort to take action in an organized sustainable approach.

In 2000-2001, Frontier Science Technology & Research Foundation offered a two day training meeting, one in Florida and another in the Philadelphia area. The first meeting in St Petersburg, Florida was held at a hotel convenient to the airport. Attendance was adequate but the lesson learned was that this was neither convenient nor cost efficient for a sponsor to send more than one or two individuals. Thus, the next offering was chosen to be in a neighborhood convenient to industry. Unfortunately, the second meeting in Philadelphia, PA area was 10 days after 9/11 and most of those who had signed up had to cancel due to travel restrictions by sponsors. Still, the course was successfully presented. After that attempt, Frontier Science did not make any further attempts to train future DMC members. Stimulated by the recent CTTI IDMC project, Frontier Science is again quite enthusiastic about hosting this training effort but adopting a slightly different approach.

While Frontier would host the training session and provide logistics, a broader team of experts from around the country, not just Frontier affiliated staff, would be organized to provide the IDMC & SDAC training. We envision several possible venues for these training sessions: 1) as part of a professional meeting similar to the approach taken at SCT and AHA; 2) on the front end or back end of a professional meeting; 3) in the geographical neighborhood of industry like Frontier did in 2001 in Philadelphia; or 4) in-house to a sponsor as many others have done periodically.

Our concept is that if a group, organization or sponsor wanted IDMC or SDAC training, Frontier Science would call upon 3-4 members of this small pool of faculty with IDMC expertise to provide a short course with topics to be suggested below but in keeping with the CTTI IDMC and other publications such as the FDA guidance document on IDMCs and the text by Ellenberg, Fleming & DeMets.

Training Faculty

Frontier Science will host an effort by a team to create such a training forum for both IDMCs and SDACs. Serving as a facilitator of such a training program as well as providing IDMC and SDAC experience of our own, we have reached out to a few selected individuals with DMC experience and related publications, both clinical and statistical, and some SDACs with known expertise and experience in providing state of the art interim IDMC reports to organize a training program, calling up this pool of individuals for specific offerings. These offerings could focus on being a member of an IDMC and best practices for SDACs.

IDMC Faculty

Raymond Bain, PhD, Merch Research Laboratories (MRL)

Prior to joining Merck in 1999, Ray Bain was Co-Director and Research Professor at the George Washington University (GWU) Biostatistics Center (1986-1999), and Coordinating Center Principle Investigator for multiple NIH sponsored clinical trials including SDAC responsibilities for NIH- and industry-sponsored trials. Also, he has been an IDMC member for government- and industry-sponsored trials. Since 2001, he has served as the Head of the MRL- BARDS (Biostatistics and Research Decision Sciences) organization with oversight for the design, execution and analysis of Merck-sponsored clinical trials including Merck-sponsorship of IDMCs. Currently, he is a member of multiple IDMCs for NIH-sponsored trials. From 2014 through 2017 he was a team co-leader (industry representative) for the Clinical Trials Transformation Initiative (CTTI) IDMC project. He is a fellow of the SCT and ASA.

Thomas Cook, PhD, University of Wisconsin Madison

Thomas Cook received his PhD from the University of Wisconsin, Madison in 1993 and now is Senior Scientist Biostatistician at the SDAC in the Department of Biostatistics and Medical Informatics. A primary area of interest is the design, monitoring and analysis of controlled clinical trials. Specific interests include methods for adjusting sample sizes/recruitment rates in order to maintain study power as trials unfold and interim data becomes available. He has made available software with which to facilitate such decisions for trials with survival endpoints. Another issue in the interim monitoring of clinical trials with survival endpoints is the incompleteness of interim data, specifically those attributed to delays in reporting potential primary events as well as to delays in the adjudication of reported events. He has developed methods for accounting for delays in adjudication.

Another specific interest is the production of data monitoring reports. Data monitoring reports must be produced in a timely fashion, often with large numbers of variables which must be presented in various formats. Furthermore, data monitoring committees must be able to digest the information presented quickly and accurately in order to make timely decisions regarding the conduct of the trial. The most efficient mode of presentation is usually graphical and computer software has been created to efficiently analyze large amounts of accumulating data and create useful reports.

David DeMets, PhD, University of Wisconsin Madison

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. He also was a member of FDA advisory panels in the Center for Drugs Evaluation and Research (CDER) and the Center for Devices and Radiological Health (CDRH). 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 President of 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. He received his PhD in biostatistics in 1970 from the University of Minnesota. In 2013 he was elected as a member of the Institute of Medicine of the National Academies.

Susan Ellenberg, PhD, University of Pennsylvania

Dr. Ellenberg is Professor of Biostatistics, Department of Biostatistics and Epidemiology, with a secondary appointment in the Department of Medical Ethics and Health Policy. She serves as senior statistician for several multicenter clinical trials and directs the Biostatistics Core of the Penn Center for AIDS Research. She chairs the organizing committee for the annual Penn conference on statistical issues in clinical trials. She also served for many years as Associate Dean for Clinical Research in the Perelman School of Medicine. From 1993 to 2004 she served as Director, Office of Biostatistics and Epidemiology in the Center for Biologics Evaluation and Research (CBER) at the U.S. Food and Drug Administration; prior to that she served as the first Chief of the Biostatistics Research Branch in the Division of AIDS, NIAID (1988-1993), and served in the Biometric Research Branch in the Cancer Therapy Evaluation Program, NCI (1982-1988). She has served on numerous data monitoring committees for federally- and industry-funded clinical trials.

Dr. Ellenberg is a Fellow of the American Statistical Association, the Society for Clinical Trials, and the American Association for the Advancement of Science, and is an elected member of the International Statistical Institute. Her book, Data Monitoring Committees in Clinical Trials: A Practical Perspective, co-authored with Drs. Thomas Fleming and David DeMets, was named Wiley Europe Statistics Book of the Year for 2002; now in its second edition.

Scott Evans, PhD, George Washington University Biostatistics Center

Scott Evans, PhD, Director of the Biostatistics Center and Professor in the Department of Epidemiology and Biostatistics at George Washington University, is the Director of the Statistical and Data Management Center (SDMC) for the Antibacterial Resistance Leadership Group (ARLG). He is a member of the Board of Directors for the American Statistical Association (ASA) and the Society for Clinical Trials (SCT), an FDA Advisory Committee, and the Steering Committee of the Clinical Trials Transformation Initiative (CTTI). Dr. Evans has served on numerous DSMBs for government and industry-sponsored clinical trials including as Chair of the DSMBs for the Adolescent Trials Network (ATN) and for a clinical trial of microbial restoration in Clostridium difficile associated disease (CDAD), an .urgent. hazard level pathogen. He has been the Director of multiple SDACs that prepare reports for DSMBs and has taught short courses on DSMBs at professional meetings such as the SCT.

Thomas Fleming, PhD, University of Washington

Dr. Fleming is Professor of the Department of Biostatistics, Member of the Fred Hutchinson Cancer Research Center and the former Director of the Statistical Center for HIV/AIDS Prevention Trial Network, NIAID. He 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 more than 25 years he has served as a regular member of several FDA Advisory Committees or as an invited voting member. 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. In 2012 he was elected to membership in the Institute of Medicine of the National Academies

Christopher Granger, MD, Duke University Medical Center

Dr. Granger is Professor of Medicine at the Duke University Medical Center. Dr. Granger graduated from University of Connecticut School of Medicine in 1984. His primary research interest is in conduct and methodology of large randomized clinical trials in heart disease. He has led a number of large international clinical studies in heart attacks, unstable angina, heart failure, and atrial fibrillation. He has lead clinical studies of blood thinners and coronary intervention for heart attacks, stroke prevention in atrial fibrillation, and prevention of heart attack for patients with coronary artery disease. He serves as the Chairman of the American Heart Association “Mission: Lifeline” program to improve heart attack care nationally as well as the American College of Cardiology/American Heart Association guideline committee for heart attack care. He works with the National Institutes of Health and the Federal Drug Administration on evaluation of heart disease and of new drugs. He has developed tools to predict which patients are at risk for death, heart attack, and need for hospitalization. He has served on many IDMCs as well as being the chair for several of them.

Charles Hennekens, MD/DrPH, Florida Atlantic University

Currently Dr. Hennekens serves as the first Sir Richard Doll Professor at the Charles E. Schmidt College of Medicine at Florida Atlantic University. From 1975 to 1999 he was on the faculty in the Harvard Medical School and the School of Public Health. He was formerly the first John Snow Professor of Medicine and first Eugene Braunwald Professor of Medicine at Harvard Medical School. He received his MD in 1967 from Cornell and his DrPH in epidemiology from the Harvard School of Public Health in 1975. He has published 900 papers on his observational studies and clinical trial research for cardiovascular disease and cancer. He has made seminal research discoveries on aspirin in the treatment and prevention of cardiovascular disease as well as on statins and angiotensin converting enzyme inhibitors. He is a Fellow of the American College of Preventive Medicine (FACPM) and the American College of Cardiology (FACC) and has won many other prestigious awards including the James T. and Sara Freis Prize for Improving Health and Alton Ochsner Award Relating Smoking and Disease. He currently serves as Chair of 8 IDMCs and a member of 2.

James Neaton, PhD, University of Minnesota

Jim Neaton is Professor in the Division of Biostatistics at the University of Minnesota School of Public Health. Having served his Public Health Service appointment at the NIH 1970-1972, he returned to the University of Minnesota in 1973 to join in the data coordinating center for Multiple Risk Factor Intervention Trial (MRFIT) and ultimately became its Director. He went on to successfully lead the data coordinating center for several other important cardiovascular trials sponsored by the NIH as well as by industry, and a major data coordinating center for the study of AIDS and possible interventions and treatments. He provided leadership in the SMART and START trials in HIV infected patients, two of the three major breakthrough studies in HIV research. He leads a large network called INSIGHT that conducts international trials of HIV and influenza treatments, and conducts observational studies of C. difficile infection and influenza. He also leads research on Ebola in West Africa that includes clinical trials of vaccines and treatments, and a large cohort study of Ebola survivors and their close contacts.

He served as editor in chief of the Journal of Controlled Clinical Trials (1999-2003) and by being President of the Society for Clinical Trials (2006-2007). In addition, he has served on the FDA Cardiovascular and Renal Drugs Advisory Committee, 2007- 2011, and the FDA Endocrinology and Metabolic Drugs Advisory Committee, 2014-Present.

Marc Pfeffer, MD/PhD, Harvard University

Marc Pfeffer, MD/PhD is the Victor J. Dzau Professor of Medicine at Harvard Medical School and a cardiovascular medicine specialist at Brigham and Women’s Hospital (BWH). Dr. Pfeffer received his medical degree from University of Oklahoma College of Medicine in 1976. Dr. Pfeffer is board certified in internal medicine, cardiovascular disease, and advanced heart failure and transplant cardiology.

Dr. Pfeffer, along with Dr. Janice Pfeffer and Dr. Eugene Braunwald, is credited with introducing the concept that angiotensin-converting enzyme inhibitors (ACEIs) could mitigate adverse ventricular remodeling following myocardial infarction and that would result in increased survival and other clinical benefits. His general clinical interests include cardiovascular disease, congestive heart failure, coronary artery disease and valvular heart disease. The author of over 450 peer-reviewed publications, Dr. Pfeffer is the recipient of the Clinical Research Prize and the James Herrick Award, both from the American Heart Association.

He has served as the principal investigator for numerous trials including ELIXA and numerous DMCs.

Stuart Pocock, PhD, London School of Hygiene and Tropical Medicine

Stuart J. Pocock is Professor of Medical Statistics at the London School of Hygiene and Tropical Medicine.

His primary research interest concerns clinical trials, both as regards methodological developments and applied collaboration in major trials. He also has interests in observational epidemiology especially pharmaco-epidemiology. His particular methodological areas of expertise include: standards for the statistical reporting of trials and epidemiological studies, the statistical ethical and organisational principles for data monitoring including early stopping guidelines, the presentation of time-to-event (survival) data, the pros and cons of non-inferiority trials, problems of multiplicity in trial reporting, eg, subgroup analyses, multiple outcomes and covariate adjustment, the development of prognostic risk scores, and the use/interpretation of meta-analyses.

Professor Pocock runs a statistical centre for the design, conduct, analysis and reporting of major clinical trials, especially in cardiovascular diseases. He is also a consultant statistician for a wider range of clinical trials in which expert statistical advice is needed, and serves as a statistical member of many trial data monitoring and steering committees.

He collaborates internationally especially with the Centro Nacional de Investigaciones Cardiovasculares in Madrid, and the Cardiovascular Research Foundation and Mount Sinai School of Medicine in New York. He is a frequent lecturer on a variety of clinical trials issues.

He is Member of the Advisory Board of Trials, author of the textbook Clinical Trials: A Practical Approach, and Member of the International Advisory Board of The Lancet.

Professor Pocock has published over 300 articles in peer-reviewed journals.

Frank Rockhold, ScM, PhD, Duke University

Frank Rockhold is Professor of Biostatistics at Duke University and a member of the Duke Clinical Research Institute. Prior to joining the Duke faculty, Frank’s career included senior research positions at Lilly Research Laboratories, Merck Research Laboratories and GlaxoSmithKline, where he recently retired as Senior Vice President of Global Clinical Safety and Pharmacovigilance. He has been a leader in the scientific community in promoting data disclosure and transparency in clinical research. He has served on 10 IDMCs, chairing 3 of them. He sponsored >100 IDMCs while at GSK and approved all charters and wrote all charter templates. Frank is past president of the Society for Clinical Trials. He is a member of the PCORI Advisory Panel on Clinical Trials and is on the board of the Frontier Science and Technology Research Foundation. He holds a PhD in Biostatistics from the Medical College of Virginia. He is a Fellow of both the American Statistical Association and the Society for Clinical Trials.

Jean Rouleau, MD, Montreal University

Dr. Rouleau is past Dean of the University of Montreal’s Faculty of Medicine and practices cardiology at the Montreal Heart Institute. He has also served as a member of the Canadian Institute for Health Research (CIHR) Governing Council since 2005. A respected cardiologist and world-famous researcher, Dr. Rouleau previously taught at the University of Toronto and served as Director of the Cardiac Program and the cardiology departments at Toronto’s University Health Network (UNH) and at Mount Sinai Hospital. He earned his M.D. degree from the University of Ottawa, and completed his clinical training at McGill University followed by postdoctoral research in San Francisco.

Steven Snapinn, PhD, Amgen

Steven Snapinn is Vice President of Global Biostatistical Science at Amgen for the past 14 years. This department provides biostatistical and statistical programming support to all phases of Amgen’s drug development programs. Prior to Amgen, for 20 years, Steve was Senior Director of Biostatistics at Merck. Dr. Snapinn received his Ph.D. from the University of North Carolina at Chapel Hill in 1983. He is former editor of Statistics in Biopharmaceutical Research and is a fellow of the American Statistical Association. He has approximately 100 publications in the statistical and medical literature.

Janet Wittes, PhD, Statistics Collaborative

Janet Wittes, PhD, founded Statistics Collaborative, Inc. (SCI) in 1990. She is a Fellow of the American Statistical Association, the Society for Clinical Trials (SCT), and the American Association for the Advancement of Science, and an elected member of the International Statistical Institute. She was President of the International Biometric Society Eastern North American Region in 1995, and on the Board of Directors 1990-1998, and President 2001 for the SCT. Formerly Editor-in-Chief of Controlled Clinical Trials, the official journal of the SCT, she is an Associate Editor of SCT’s current journal, Clinical Trials. She co-authored monograph on group sequential trials (Proschan M, Lan K, Wittes J. Statistical Monitoring of Clinical Trials: A Unified Approach. New York: Springer, 2006.). She is a member of a many Data Monitoring Committees (DMCs) for randomized clinical trials with industry or government sponsors. She chairs the DMCs for several large multi-center trials sponsored by the National Institutes of Health (NIH). She is a current member of the Food and Drug Administration (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee. She previously served a four-year term as a member of the Circulatory System Devices Panel (1999-2003) and has been a member of several ad hoc FDA Advisory Panels. She received her Ph.D. in Statistics from Harvard University in 1970.

SDAC Training Leaders

Kevin Buhr, PhD, University of Wisconsin, Madison

Kevin Buhr, PhD, Senior Scientist. Kevin is the Director of the University of Wisconsin Statistical Data Analysis Center and has spent the past decade providing independent statistical support to Data Monitoring Committees for industry-sponsored Phase 2 and 3 clinical trials. He has led statistical reporting teams for 15 clinical trial programs involving approximately 50 trials and 120,000 patients. He also teaches courses and workshops for clinicians on the topic of good practices for clinical study design, and he collaborates with academic researchers in clinical and veterinary departments at the University. He earned his PhD in Statistics at the University of Wisconsin.

Jamie Hoel, MS, Frontier Science, Madison

Jamie Hoel joined Frontier Science in 2004. He received a Master of Science in Biostatistics from the University of Minnesota (2004). He served as a Biostatistician at Frontier Science until 2015 when he was appointed Associate Director of the Madison office. In 2018 he was appointed Director of the Madison office. He has served as lead statistician and provided biostatistical support and direction in a wide range of disease areas for SDACs supporting IDMCs, including but not limited to Relapsing Multiple Sclerosis, Secondary Hyperparathyroidism, Atrial Fibrillation, Atrial Flutter, Acute Decompensated Heart Failure, Dyslipidemia, Breast Cancer, Clostridium Difficile-Associated Diarrhea, Diabetes, Insomnia, Pulmonary Arterial Hypertension, and Menke’s Disease.

David Kerr, MS, Axio, Seattle

David Kerr has worked at Axio Research in Seattle for the past 22 years and is the Director of DMC Services. David has provided statistical support as the Independent Statistician for the SDAC for more than 100 IDMCs covering 150 individual clinical trials and attended 500 DMC meetings. He has presented on IDMC methods and procedures at Joint Statistical Meetings (JSM) and SCT, and also has made regular visits to industry sponsors to train on the IDMC process.

Janelle Rhorer, MS, Statistics Collaborative, Washington DC

For more than 15 years Ms. Rhorer has supported Data Monitoring Committees (DMCs) as the independent reporting statistician. In this role, she has developed interim analysis plans, drafted DMC charters, managed teams of programmers, and written and presented interim monitoring reports to DMCs for large, multi-center Phase 2 and 3 clinical trials including oncology, cardiovascular diseases, influenza, ophthalmologic diseases, rare neuromuscular disorders, and psychiatric disorders. Several of these projects have been in support of a single DMC overseeing multi-study development programs.

Training Forums

Specific training offerings could take place in various forums. For example, training courses on specific topics might take place in conjunction with an annual professional meeting such as the American Heart Association (AHA), the American Society for Clinical Oncology (ASCO) or the American Diabetes Association (ADA), either 1) as an independent offering or 2) as part of their continuing medical education (CME) efforts. Training offering could also be presented 3) on site at major pharmaceutical or device companies or 4) offered separately but in a convenient geographic location (e.g., the Philadelphia area).

Administrative Support

The Frontier Science Madison Office has agreed to host or facilitate these training opportunities to help with travel logistics, meeting organization and advertisement on behalf of the IDMC training faculty and SDAC teams.

Registration fees would cover faculty travel expenses and meeting costs. As a public service and a commitment to training the next generation, no honoraria for faculty are provided.

Training Curriculum

While inter-related, two basic training modules will be offered, one focused on IDMC membership and a second on the SDAC report generation and IDMC statistical support.

IDMC Training Session

  • Topic 1: Why are we here? Background on the IDMC development
  • Topic 2: What does a sponsor need to know about IDMCs and SDACs
    • Government vs Industry variations
    • Maintaining sponsor independence of IDMC and SDAC
    • To whom does the IDMC report?
  • Topic 3: Basic Responsibilities of IDMCs and their membership
    • Review of protocol and data collection process
    • Review of IDMC Report Content and SDAC role
    • Review of statistical analysis plan
  • Topic 4: IDMC Charters and Member Contracts
    • Need for flexibility in Charters
    • Contracts addressing COI and Indemnification
  • Topic 5: Chairing an IDMC
  • Topic 6: Statistical Monitoring Methods 101
    • Group sequential methods
    • Conditional power and futility
    • Alpha allocation across multiple hypotheses
  • Topic 7: What IDMCs Should Know about SDACs
  • Topic 8: Case Studies Review (eg DeMets et al: a case studies approach)
  • Topic 9: IDMC Simulation: a presentation of the series of IDMC reports for a particular trial, and issues/recommendations made by the DMC for each meeting/using 2-3 completed trials

SDAC Training Session

  • Understanding the role of the IDMC and its relation to
    • the independent statistician and
    • the SDAC
  • Confidentiality of
    • Data Reports and
    • IDMC Deliberations
    • Raw data including ancillary data
    • Updates on other sponsor trials
  • Understanding the protocol and data collection/case report forms
  • Participation in the IDMC Charter development
  • Data transfer from data management organizations to the SDAC
    • frequency
    • completeness
    • validation
  • Development of an SAP tailored to the needs of the IDMC
  • Internal validation of interim analyses
  • Content of an IDMC report
    • The open report
    • The closed report
  • Presentation style with emphasis on graphics
  • SDAC interactions with IDMC during meetings & IDMC Chair overall
  • Need for flexibility to respond to IDMC needs
  • How to structure contracts between the SDAC and the Sponsor
  • Which SDAC members should attend the IDMC meetings?
  • Relationship between IDMC, Sponsor, Executive Committee, CRO
  • Who should talk to whom?
  • Meeting Logistics
    • Taking Minutes of IDMC meeting
    • Organizing TC & Web Conferences
    • Securely sending out interim IDMC Reports
    • Working with sponsor on travel logistics if appropriate
  • Internal SDAC staff training

Some References

  • Ellenberg S, Fleming T and DeMets D: Data Monitoring Committees in Clinical Trials: A Practical Perspective. John Wiley & Sons, Ltd., West Sussex, England, 2002.
  • DeMets DL, Friedman L, Furberg CD. Data Monitoring in Clinical Trials: A Case Studies Approach. Springer Science+Business Media, New York, NY, 2005.
  • Evans S , Ting N; Fundamental Concepts for New Clinical Trialists, Chapman and Hall, CRC Press, Sept 25, 2015.
  • Herson J, Data and Safety Monitoring Committees in Clinical Trials, Second Edition (Chapman & Hall/CRC Biostatistics Series) 2nd Edition.
  • Lewis R, Calis K & DeMets DL, Enhancing the Scientific Integrity and Safety of Clinical Trials: Recommendations for Data Monitoring Committees from the Clinical Trials Transformation Initiative, JAMA, Dec 13 2016.
  • Pocock, Stuart (1983). Clinical Trials: A Practical Approach. Wiley-Blackwell. ISBN 978-0-471-90155-6.
  • Pitt, Bertram; Julian, Desmond Gareth; Pocock, Stuart J., eds. (1997). Clinical Trials in Cardiology. W. B. Saunders. ISBN 978-0-7020-2156.
  • Calis K, Archdeacon P, Bain R, Forrest A, Perlmutter J, DeMets D, Understanding the Functions and Operations of Data Monitoring Committees: Survey and Focus Group Findings to Clinical Trials: Journal of the Society for Clinical Trials, 2017, Vol 14: 59-66.
  • Calis K, Archdeacon P, Bain R, DeMets D, Donohue M, Elzarrad MK, Forest A, McEachern J, Pencina M, Perlmutter J, Lewis R, Recommendations for Data Monitoring Committees from the Clinical Trials Transformation Initiative, Clinical Trials, 2017 Vol 14, 342-348.
  • Fleming T, DeMets D et al, Data Monitoring Committees: Promoting Best Practices to Address Emerging Challenges, Journal of the Society for Clinical Trials, 2017, p1-9.
  • DeMets DL & Ellenberg S, Data monitoring committees: expect the unexpected, NEJM, 2016;375:1365-71.
  • Herson J. Data monitoring boards in the pharmaceutical industry. Statist Med 1993; 12:555-561.
  • Wittes J. Behind closed doors: the data monitoring board in randomized clinical trials. Statist Med 1993; 12:419-424.
  • Ref: Buhr KA, Downs M, Rhorer J, Bechhofer R, Wittes J. Reports to Independent Data Monitoring Committees: An Appeal for Clarity, Completeness, and Comprehensibility. Therapeutic Innovation & Regulatory Science. 2017 Nov 13. https://doi.org/10.1177/2168479017739268.
  • Pocock S, Wilhelmsen L, Dickstein K, Francis G, Wittes J, The data monitoring experience in the MOXCON trial European Heart Journal, Volume 25, Issue 22, 1 November 2004, Pages 1974.1978, https://doi.org/10.1016/j.ehj.2004.09.015.
  • Pocock S & Furberg C, Procedures of Data and Safety Monitoring Committees. American Heart Journal 141(2):289-94. March 2001. DOI: 10.1067/mhj.2001.113082.
  • Pocock S, McMurray J & Collier T, Making sense of statistics in clinical trial reports Part 1 of a 4 part series, J American College of Cardiology, Vol 66, No 22, 2015.