Data Monitoring Committees in Clinical Trials

Name: Data Monitoring Committees in Clinical Trials | A Practical Perspective
Brand: Wiley
Price: 102.99 EUR
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A Practical Perspective

Susan S. Ellenberg Thomas R. Fleming David DeMets(Autor*in)

Wiley (Verlag)

2. Auflage

Erschienen am 14. Januar 2019

496 Seiten

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Beschreibung

-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.

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Inhalt

Cover
Title Page
Copyright
Contents
Preface to the Second Edition
Preface to the First Edition
Chapter 1 Introduction
1.1 Motivation
1.2 History of data monitoring committees in government-sponsored trials
1.3 Data monitoring committees in trials sponsored by the pharmaceutical industry
1.4 Statistical methods for interim monitoring
1.5 When are data monitoring committees needed?
1.6 Models for data monitoring committees
1.7 Where we are today
1.8 Fundamental principles of data monitoring
References
Chapter 2 Responsibilities of the Data Monitoring Committee and Motivating Illustrations
2.1 Fundamental charges
2.2 Specific tasks of the data monitoring committee
2.2.1 Initial review
2.2.1.1 Review of the study protocol
2.2.1.2 Review of procedures to ensure quality of study conduct
2.2.2 Evaluating the quality of ongoing study conduct
2.2.3 Assessing safety and efficacy data
2.2.3.1 Termination due to favorable benefit-to-risk
2.2.3.2 Termination due to unfavorable benefit-to-risk
2.2.3.3 Termination due to inability to answer trial questions
2.2.3.4 Continuation of ongoing clinical trials
2.2.3.5 Consideration of the overall picture: primary and secondary analyses
2.2.3.6 Modifying sample sizes based on ongoing assessment of event rates
2.2.4 Reviewing the final results
2.3 The data monitoring committee charter
References
Chapter 3 Composition of a Data Monitoring Committee
3.1 Introduction
3.2 Required areas of expertise
3.3 Other relevant characteristics of committee members
3.4 Committee size
3.5 Selecting the committee chair
3.6 Responsibility for appointing committee members
3.7 Representation of other study components on the committee
3.8 Preparation for service on a committee
References
Chapter 4 Independence of the Data Monitoring Committee: Avoiding Conflicts of Interest
4.1 Introduction
4.2 Rationale for independence
4.3 Financial independence
4.3.1 Commercial sponsors
4.3.2 Government sponsors
4.3.3 Academic investigators
4.4 Intellectual independence
4.5 Emotional conflicts
4.6 Best practices to address challenges to the DMC's independence
4.6.1 Adequate training/experience in the DMC process
4.6.2 Indemnification of DMC members
4.6.3 Maintaining confidentiality of interim data
4.6.4 Flexibility of procedures
4.6.5 DMC meeting format
4.6.6 Creating independent relationships and reducing conflicts of interest
4.6.7 Adequately informative DMC reports
4.7 Summary
References
Chapter 5 Confidentiality Issues Relating to the Data Monitoring Committee
5.1 Rationale
5.2 Limits of confidentiality
5.2.1 Interim analysis reports
5.2.2 Access to aggregate data on efficacy and safety outcomes
5.2.3 Providing access to interim data on a "need-to-know" basis
5.2.4 Settings and procedures allowing broader unblinding of safety data
5.2.5 Consequences of unblinding interim data for regulatory review in ongoing trials
5.2.6 Some illustrations of broader unblinding
5.2.7 The steering committee and maintaining confidentiality
5.2.8 Indirect challenges to confidentiality
5.3 The need for the DMC to review unblinded data
5.4 Conclusions: consensus regarding confidentiality
References
Chapter 6 Data Monitoring Committee Meetings
6.1 Introduction
6.2 Specific objectives and timing of meetings
6.2.1 Organizational meeting
6.2.2 Early safety/trial integrity reviews
6.2.3 Formal interim efficacy analyses
6.2.4 End-of-trial debriefing
6.3 Preparation of meeting reports
6.3.1 Currentness of data in the report
6.3.2 Inclusion of unadjudicated data
6.4 Format for meetings
6.4.1 The initial closed session
6.4.2 The open session
6.4.3 The final closed session
6.4.4 Various formats for holding the open and closed sessions
6.4.5 Meeting duration and venue
6.5 DMC meeting minutes and the DMC recommendations
6.5.1 The DMC recommendations, the open minutes, and the closed minutes
6.5.2 The level of detail
6.5.3 The authorship of the minutes and the sign-off by committee members
References
Chapter 7 Data Monitoring Committee Interactions with Other Trial Components or Related Groups
7.1 Introduction
7.2 Study sponsors
7.2.1 Industry sponsors
7.2.2 Government sponsors
7.3 Study steering committee/principal investigator
7.4 Study investigators
7.5 Trial statisticians and statistical centers
7.5.1 The independent statistical center
7.5.2 Ensuring optimal data presentations
7.6 Institutional review boards
7.7 Regulatory agencies
7.8 Study participants and/or advocacy groups
7.9 Other data monitoring committees
References
Chapter 8 Statistical, Philosophical, and Ethical Issues in Data Monitoring
8.1 The need for statistical approaches to monitoring accumulating data
8.2 Overview of statistical methods
8.2.1 Group sequential methods
8.2.1.1 Some group sequential boundaries for establishing benefit
8.2.1.2 Group sequential alpha spending functions
8.2.1.3 Some group sequential boundaries when early results are unfavorable
8.2.2 Triangular boundaries
8.2.3 Stochastic curtailment/conditional power
8.2.4 Bayesian monitoring
8.2.5 The general approach to sequential stopping boundaries
8.2.6 Software packages for sequential clinical trial designs
8.2.7 Adaptive clinical trial designs
8.3 Protocol specification of the monitoring plan
8.4 Other statistical considerations in monitoring trial data
8.4.1 Primary versus secondary endpoints
8.4.2 Short-term versus long-term treatment effects
8.4.3 Results in subgroups
8.4.4 Taking external information into account
8.4.5 Evaluating safety in the context of evidence about efficacy: role of boundaries
8.4.6 Ensuring proper robustness when defining boundaries for establishing benefit
8.5 Ethical considerations
8.5.1 Early termination philosophies
8.5.1.1 Responding to early beneficial trends
8.5.1.2 Responding to early unfavorable trends
8.5.1.3 Responding to unexpected safety concerns
8.5.2 Other ethical considerations
References
Chapter 9 Determining When a Data Monitoring Committee is Needed
9.1 Introduction
9.2 Typical settings for an independent data monitoring committee
9.3 Other settings in which an independent data monitoring committee may be valuable
9.3.1 Early trials of high-risk treatments
9.3.2 Trials in vulnerable populations
9.3.3 Trials with potentially large public health impact
9.4 An alternative monitoring approach: the internal monitoring committee
9.5 A decision model assessing need for an independent DMC or an internal monitoring committee
9.6 Settings with little need for an independent or internal monitoring committee
9.7 Summary
References
Chapter 10 Regulatory Considerations for the Operation of Data Monitoring Committees
10.1 Introduction
10.2 Data monitoring committees in government regulations
10.3 Regulatory guidance
10.3.1 US Food and Drug Administration
10.3.2 International regulatory guidance
10.3.2.1 European Union
10.3.2.2 International Conference on Harmonization
10.3.2.3 The World Health Organization
10.4 Regulatory approaches relevant to data monitoring committee operation: the US FDA
10.5 Policies of funding agencies regarding DMC operations
10.5.1 National Institutes of Health
10.5.2 Other federal agencies
10.5.3 Funding agencies outside the US
10.6 Involvement of fda staff in data monitoring committee deliberations
10.7 Examples of regulatory authority interaction with data monitoring committees
References
Chapter 11 Legal Considerations for DMCs
11.1 DMC indemnification
11.1.1 Motivating examples
11.1.2 Emergence of DMCs and heightened awareness of their existence
11.1.3 Further motivation for indemnification to protect the DMC
11.1.4 Some specific concerns from current experiences with indemnification
11.1.5 Potential solutions to indemnification issues
11.1.6 Confidential disclosure agreement (CDA)
11.1.7 Summary of indemnification, liability, and contracting issues
11.2 Balancing legal and ethical responsibilities: a need for a mediator?
11.2.1 A case study: the setting of Actimmune in patients with idiopathic pulmonary fibrosis
11.2.2 IMMUNE response AIDS clinical trial
References
Appendix A The Data Monitoring Committee Charter
Appendix B Performance Standards Document
Statistics in Practice
Index
EULA

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