Data And Safety Monitoring Committees In Clinical Trials

Focusing on the practical clinical and statistical issues that arise in pharmaceutical industry trials, this book summarizes the author’s experience in serving on many data monitoring committees (DMCs) and in heading up a contract research organization that provided statistical support to nearly seventy-five DMCs. It explains the difference in DMC operations between the pharmaceutical industry and National Institutes of Health (NIH)-sponsored trials. Leading you through the types of reports for adverse events and lab values, the author presents the statistical requirements of data monitoring committees and gives advice on how statisticians can best interact with physician members of these committees. He also shows how physicians think differently about safety data than statisticians, proving that both views are needed.

A key function during clinical trials is the Data Safety Monitoring Board (DSMB). The board is composed of several experts who review the investigational trial and receive unblinded data from the clinical investigator as well as the study sponsor. The unblinded data can be reviewed to determine if an adverse event is relevant to the study. The DSMB has the authority, if necessary, to stop the study at an appropriate juncture. There are two modules that present the concept of the DSMB, with specific detail related to investigational studies where the establishment of the DSMB is warranted. The key factor of reviewing an adverse event at an investigational site allows the DSMB to assess the risks in the study. The DSMB is established by charter detailing the scope of the board's authority, the composition of its members, how often the board will meet, and the types of meetings the board will conduct. In addition, the board must be grounded in the design types of studies so they are appreciative of the way the investigational trial will be conducted. Module B continues with different phases of clinical trials, with a key discussion of the study types where a DSMB is mandated. the board must also be aware of the FDA's recall system since it may affect the ongoing investigational trial. The review continues with the types of meetings undertaken by the DSMB, to include information obtained from the Department of Defense Research Monitor who may be a DSMB voting member. The module then reviews the specific actions the DSMB may take during the study, with practical recommendations the board should consider during its meetings. A critical aspect of the board's responsibility is its communication with the institutional review board (IRB (whether a specific IRB or a multiplicity of different IRBs. While the IRB does not receive unblinded data, the DSMB only receives unblinded data, so that communication with the IRB, by necessity, is restricted to data that can be shared with the IRB. However, if the DSMB stops a study, the IRB must be notified immediately so that the study's approval can be withdrawn. The scope of the duties of the DSMB is to provide the members with key data so as to protect the study subjects and ensure the trial is conducted in an optimal manner.

The authoritative guide for Data Monitoring Committees—fully revised and updated The number of clinical trials sponsored by government agencies and pharmaceutical companies has grown in recent years, prompting an increased need for interim monitoring of data on safety and efficacy. Data Monitoring Committees (DMCs) are an essential component of many clinical trials, safeguarding trial participants and protecting the credibility and validity of the study. Data Monitoring Committees in Clinical Trials: A Practical Perspective, 2nd Edition offers practical advice for those managing and conducting clinical trials and serving on Data Monitoring Committees, providing a practical overview of the establishment, purpose, and responsibilities of these committees. Examination of topics such as the composition and independence of DMCs, statistical, philosophical and ethical considerations, and determining when a DMC is needed, presents readers with a comprehensive foundational knowledge of clinical trial oversight. Providing recent examples to illustrate DMC principles, this fully-updated guide reflects current developments and practices in clinical trial oversight and offers expanded coverage of emerging issues and challenges in the field. This new second edition covers the most current information on DMC policies, issues in monitoring trials using new designs, and recent trial publications relevant to DMC decision-making. • Presents practical advice for those managing and conducting clinical trials and serving on Data Monitoring Committees • Illustrates the types of challenging issues Data Monitoring Committees face in practical situations • Provides updated and expanded coverage of topics including regulatory and funding agency guidelines and trial designs and their associated demands and limitations • Includes a new chapter addressing legal issues that affect DMC members and discusses general litigation concerns relevant to clinical research • Expands treatment of current journal publications addressing DMC issues Data Monitoring Committees in Clinical Trials: A Practical Perspective, 2nd Edition is a must-have text for anyone engaged in DMC activities as well as trial sponsors, clinical trial researchers, regulatory and bioethics professionals, and those associated with clinical trials in academic, government and industry settings.

­The authoritative guide for Data Monitoring Committees—fully revised and updated The number of clinical trials sponsored by government agencies and pharmaceutical companies has grown in recent years, prompting an increased need for interim monitoring of data on safety and efficacy. Data Monitoring Committees (DMCs) are an essential component of many clinical trials, safeguarding trial participants and protecting the credibility and validity of the study. Data Monitoring Committees in Clinical Trials: A Practical Perspective, 2nd Edition offers practical advice for those managing and conducting clinical trials and serving on Data Monitoring Committees, providing a practical overview of the establishment, purpose, and responsibilities of these committees. Examination of topics such as the composition and independence of DMCs, statistical, philosophical and ethical considerations, and determining when a DMC is needed, presents readers with a comprehensive foundational knowledge of clinical trial oversight. Providing recent examples to illustrate DMC principles, this fully-updated guide reflects current developments and practices in clinical trial oversight and offers expanded coverage of emerging issues and challenges in the field. This new second edition covers the most current information on DMC policies, issues in monitoring trials using new designs, and recent trial publications relevant to DMC decision-making. • Presents practical advice for those managing and conducting clinical trials and serving on Data Monitoring Committees • Illustrates the types of challenging issues Data Monitoring Committees face in practical situations • Provides updated and expanded coverage of topics including regulatory and funding agency guidelines and trial designs and their associated demands and limitations • Includes a new chapter addressing legal issues that affect DMC members and discusses general litigation concerns relevant to clinical research • Expands treatment of current journal publications addressing DMC issues Data Monitoring Committees in Clinical Trials: A Practical Perspective, 2nd Edition is a must-have text for anyone engaged in DMC activities as well as trial sponsors, clinical trial researchers, regulatory and bioethics professionals, and those associated with clinical trials in academic, government and industry settings.

From the authors of "Fundamentals of Clinical Trials" which has sold over 15,000 copies world wide since its publication in 1998. No competition yet as the text does not focus on how to do clinical trials but on very specific situations that can be encountered during the process.

Praise for the first edition: "Given the author’s years of experience as a statistician and as a founder of the first DMC in pharmaceutical industry trials, I highly recommend this book—not only for experts because of its cogent and organized presentation, but more importantly for young investigators who are seeking information about the logistical and philosophical aspects of a DMC." -S. T. Ounpraseuth, The American Statistician ? In the first edition of this well-regarded book, the author provided a groundbreaking and definitive guide to best practices in pharmaceutical industry data monitoring committees (DMCs). Maintaining all the material from the first edition and adding substantial new material, Data and Safety Monitoring Committees in Clinical Trials, Second Edition is ideal for training professionals to serve on their first DMC as well as for experienced clinical and biostatistical DMC members, sponsor and regulatory agency staff. The second edition guides the reader through newly emerging DMC responsibilities brought about by regulations emphasizing risk vs benefit and the emergence of risk-based monitoring. It also provides the reader with many new statistical methods, clinical trial designs and clinical terminology that have emerged since the first edition. The references have been updated and the very popular end-of-chapter Q&A section has been supplemented with many new experiences since the first edition. ? New to the Second Edition: Presents statistical methods, tables, listings and graphs appropriate for safety review, efficacy analysis and risk vs benefit analysis, SPERT and PRISMA initiatives. Newly added interim analysis for efficacy and futility section. DMC responsibilities in SUSARs (Serious Unexpected Serious Adverse Reactions), basket trials, umbrella trials, dynamic treatment strategies /SMART trials, pragmatic trials, biosimilar trials, companion diagnostics, etc. DMC responsibilities for data quality and fraud detection (Fraud Recovery Plan) Use of patient reported outcomes of safety Use of meta analysis and data outside the trial New ideas for training and compensation of DMC members ? Jay Herson is Senior Associate, Biostatistics, Johns Hopkins Bloomberg School of Public Health where he teaches courses on clinical trials and drug development based on his many years experience in clinical trials in academia and the pharmaceutical industry. ? ? ? ? ? ? ? ? ? ? ? ? ?

When 18-year-old Jesse Gelsinger died in a gene transfer study at the University of Pennsylvania, the national spotlight focused on the procedures used to ensure research participants' safety and their capacity to safeguard the well-being of those who volunteer for research studies. Responsible Research outlines a three-pronged approach to ensure the protection of every participant through the establishment of effective Human Research Participant Protection Programs (HRPPPs). The approach includes: Improved research review processes, Recognition and integration of research participants' contributions to the system, and Vigilant maintenance of HRPPP performance. Issues addressed in the book include the need for in-depth, complimentary reviews of science, ethics, and conflict of interest reviews; desired qualifications for investigators and reviewers; the process of informed consent; federal and institutional oversight; and the role of accreditation. Recommendations for areas of key interest include suggestions for legislative approaches, compensation for research-related injury, and the refocusing of the mission of institutional review boards. Responsible Research will be important to anyone interested in the issues that are relevant to the practice of using human subjects as research participants, but especially so to policy makers, research administrators, investigators, and research sponsorsâ€"but also including volunteers who may agree to serve as research participants.

A key function during clinical trials is the Data Safety Monitoring Board (DSMB). The board is composed of several experts who review the investigational trial and receive unblinded data from the clinical investigator as well as the study sponsor. The unblinded data can be reviewed to determine if an adverse event is relevant to the study. The DSMB has the authority, if necessary, to stop the study at an appropriate juncture. There are two modules that present the concept of the DSMB, with specific detail related to investigational studies where the establishment of the DSMB is warranted. The key factor of reviewing an adverse event at an investigational site allows the DSMB to assess the risks in the study. The DSMB is established by charter detailing the scope of the board's authority, the composition of its members, how often the board will meet, and the types of meetings the board will conduct. In addition, the board must be grounded in the design types of studies so they are appreciative of the way the investigational trial will be conducted. Module B continues with different phases of clinical trials, with a key discussion of the study types where a DSMB is mandated. the board must also be aware of the FDA's recall system since it may affect the ongoing investigational trial. The review continues with the types of meetings undertaken by the DSMB, to include information obtained from the Department of Defense Research Monitor who may be a DSMB voting member. The module then reviews the specific actions the DSMB may take during the study, with practical recommendations the board should consider during its meetings. A critical aspect of the board's responsibility is its communication with the institutional review board (IRB (whether a specific IRB or a multiplicity of different IRBs. While the IRB does not receive unblinded data, the DSMB only receives unblinded data, so that communication with the IRB, by necessity, is restricted to data that can be shared with the IRB. However, if the DSMB stops a study, the IRB must be notified immediately so that the study's approval can be withdrawn. The scope of the duties of the DSMB is to provide the members with key data so as to protect the study subjects and ensure the trial is conducted in an optimal manner.