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Data Monitoring Committees in Clinical Trials: A Practical Perspective 2nd edition [Kõva köide]

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(University of Pennsylvania), (University of Washington), (University of Wisconsin-Madison)
  • Formaat: Hardback, 496 pages, kõrgus x laius x paksus: 229x160x28 mm, kaal: 726 g
  • Sari: Statistics in Practice
  • Ilmumisaeg: 22-Mar-2019
  • Kirjastus: John Wiley & Sons Inc
  • ISBN-10: 1119512654
  • ISBN-13: 9781119512653
Teised raamatud teemal:
Data Monitoring Committees in Clinical Trials: A Practical Perspective 2nd editionSuurem pilt
  • Formaat: Hardback, 496 pages, kõrgus x laius x paksus: 229x160x28 mm, kaal: 726 g
  • Sari: Statistics in Practice
  • Ilmumisaeg: 22-Mar-2019
  • Kirjastus: John Wiley & Sons Inc
  • ISBN-10: 1119512654
  • ISBN-13: 9781119512653
Teised raamatud teemal:
Püsilink: https://www.kriso.ee/db/9781119512653.html
Märksõnad:
­The authoritative guide for Data Monitoring Committeesfully 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.
Preface to the Second Edition xiii
Preface to the First Edition xv
1 Introduction
1(34)
1.1 Motivation
1(7)
1.2 History of data monitoring committees in government-sponsored trials
8(7)
1.3 Data monitoring committees in trials sponsored by the pharmaceutical industry
15(3)
1.4 Statistical methods for interim monitoring
18(3)
1.5 When are data monitoring committees needed?
21(1)
1.6 Models for data monitoring committees
22(2)
1.7 Where we are today
24(1)
1.8 Fundamental principles of data monitoring
25(2)
References
27(8)
2 Responsibilities of the Data Monitoring Committee and Motivating Illustrations
35(54)
2.1 Fundamental charges
36(3)
2.2 Specific tasks of the data monitoring committee
39(44)
2.2.1 Initial review
40(1)
2.2.1.1 Review of the study protocol
40(5)
2.2.1.2 Review of procedures to ensure quality of study conduct
45(2)
2.2.2 Evaluating the quality of ongoing study conduct
47(9)
2.2.3 Assessing safety and efficacy data
56(2)
2.2.3.1 Termination due to favorable benefit-to-risk
58(5)
2.2.3.2 Termination due to unfavorable benefit-to-risk
63(2)
2.2.3.3 Termination due to inability to answer trial questions
65(3)
2.2.3.4 Continuation of ongoing clinical trials
68(4)
2.2.3.5 Consideration of the overall picture: primary and secondary analyses
72(4)
2.2.3.6 Modifying sample sizes based on ongoing assessment of event rates
76(4)
2.2.4 Reviewing the final results
80(3)
2.3 The data monitoring committee charter
83(1)
References
84(5)
3 Composition of a Data Monitoring Committee
89(24)
3.1 Introduction
89(1)
3.2 Required areas of expertise
90(6)
3.3 Other relevant characteristics of committee members
96(2)
3.4 Committee size
98(4)
3.5 Selecting the committee chair
102(1)
3.6 Responsibility for appointing committee members
102(2)
3.7 Representation of other study components on the committee
104(2)
3.8 Preparation for service on a committee
106(3)
References
109(4)
4 Independence of the Data Monitoring Committee: Avoiding Conflicts of Interest
113(34)
4.1 Introduction
113(1)
4.2 Rationale for independence
114(2)
4.3 Financial independence
116(9)
4.3.1 Commercial sponsors
117(1)
4.3.2 Government sponsors
118(1)
4.3.3 Academic investigators
118(7)
4.4 Intellectual independence
125(7)
4.5 Emotional conflicts
131
4.6 Best practices to address challenges to the DMC's independence
132(11)
4.6.1 Adequate training/experience in the DMC process
133(2)
4.6.2 Indemnification of DMC members
135(1)
4.6.3 Maintaining confidentiality of interim data
136(2)
4.6.4 Flexibility of procedures
138(1)
4.6.5 DMC meeting format
139(2)
4.6.6 Creating independent relationships and reducing conflicts of interest
141(1)
4.6.7 Adequately informative DMC reports
142(1)
4.7 Summary
143(1)
References
144(3)
5 Confidentiality Issues Relating to the Data Monitoring Committee
147(56)
5.1 Rationale
147(12)
5.2 Limits of confidentiality
159(31)
5.2.1 Interim analysis reports
159(2)
5.2.2 Access to aggregate data on efficacy and safety outcomes
161(3)
5.2.3 Providing access to interim data on a "need-to-know" basis
164(2)
5.2.4 Settings and procedures allowing broader unblinding of safety data
166(2)
5.2.5 Consequences of unblinding interim data for regulatory review in ongoing trials
168(7)
5.2.6 Some illustrations of broader unblinding
175(12)
5.2.7 The steering committee and maintaining confidentiality
187(2)
5.2.8 Indirect challenges to confidentiality
189(1)
5.3 The need for the DMC to review unblinded data
190(5)
5.4 Conclusions: consensus regarding confidentiality
195(3)
References
198(5)
6 Data Monitoring Committee Meetings
203(34)
6.1 Introduction
203(1)
6.2 Specific objectives and timing of meetings
204(10)
6.2.1 Organizational meeting
205(3)
6.2.2 Early safety/trial integrity reviews
208(4)
6.2.3 Formal interim efficacy analyses
212(1)
6.2.4 End-of-trial debriefing
213(1)
6.3 Preparation of meeting reports
214(7)
6.3.1 Currentness of data in the report
217(3)
6.3.2 Inclusion of unadjudicated data
220(1)
6.4 Format for meetings
221(9)
6.4.1 The initial closed session
223(1)
6.4.2 The open session
224(3)
6.4.3 The final closed session
227(1)
6.4.4 Various formats for holding the open and closed sessions
227(2)
6.4.5 Meeting duration and venue
229(1)
6.5 DMC meeting minutes and the DMC recommendations
230(5)
6.5.1 The DMC recommendations, the open minutes, and the closed minutes
230(2)
6.5.2 The level of detail
232(1)
6.5.3 The authorship of the minutes and the sign-off by committee members
233(2)
References
235(2)
7 Data Monitoring Committee Interactions with Other Trial Components or Related Groups
237(28)
7.1 Introduction
238(1)
7.2 Study sponsors
238(5)
7.2.1 Industry sponsors
239(2)
7.2.2 Government sponsors
241(2)
7.3 Study steering committee/principal investigator
243(4)
7.4 Study investigators
247(1)
7.5 Trial statisticians and statistical centers
247(6)
7.5.1 The independent statistical center
248(5)
7.5.2 Ensuring optimal data presentations
253(1)
7.6 Institutional review boards
253(3)
7.7 Regulatory agencies
256(1)
7.8 Study participants and/or advocacy groups
257(2)
7.9 Other data monitoring committees
259(3)
References
262(3)
8 Statistical, Philosophical, and Ethical Issues in Data Monitoring
265(70)
8.1 The need for statistical approaches to monitoring accumulating data
266(4)
8.2 Overview of statistical methods
270(29)
8.2.1 Group sequential methods
271(2)
8.2.1.1 Some group sequential boundaries for establishing benefit
273(4)
8.2.1.2 Group sequential alpha spending functions
277(3)
8.2.1.3 Some group sequential boundaries when early results are unfavorable
280(4)
8.2.2 Triangular boundaries
284(2)
8.2.3 Stochastic curtailment/conditional power
286(4)
8.2.4 Bayesian monitoring
290(3)
8.2.5 The general approach to sequential stopping boundaries
293(1)
8.2.6 Software packages for sequential clinical trial designs
294(1)
8.2.7 Adaptive clinical trial designs
294(5)
8.3 Protocol specification of the monitoring plan
299(1)
8.4 Other statistical considerations in monitoring trial data
300(13)
8.4.1 Primary versus secondary endpoints
300(2)
8.4.2 Short-term versus long-term treatment effects
302(1)
8.4.3 Results in subgroups
303(4)
8.4.4 Taking external information into account
307(2)
8.4.5 Evaluating safety in the context of evidence about efficacy: role of boundaries
309(2)
8.4.6 Ensuring proper robustness when defining boundaries for establishing benefit
311(2)
8.5 Ethical considerations
313(22)
8.5.1 Early termination philosophies
313(1)
8.5.1.1 Responding to early beneficial trends
314(4)
8.5.1.2 Responding to early unfavorable trends
318(6)
8.5.1.3 Responding to unexpected safety concerns
324(1)
8.5.2 Other ethical considerations
325(1)
References
326(9)
9 Determining When a Data Monitoring Committee is Needed
335(20)
9.1 Introduction
336(1)
9.2 Typical settings for an independent data monitoring committee
336(3)
9.3 Other settings in which an independent data monitoring committee may be valuable
339(3)
9.3.1 Early trials of high-risk treatments
339(1)
9.3.2 Trials in vulnerable populations
340(1)
9.3.3 Trials with potentially large public health impact
341(1)
9.4 An alternative monitoring approach: the internal monitoring committee
342(4)
9.5 A decision model assessing need for an independent DMC or an internal monitoring committee
346(5)
9.6 Settings with little need for an independent, or internal monitoring committee
351(1)
9.7 Summary
352(3)
References
353(2)
10 Regulatory Considerations for the Operation of Data Monitoring Committees
355(28)
10.1 Introduction
356(1)
10.2 Data monitoring committees in government regulations
356(1)
10.3 Regulatory guidance
357(7)
10.3.1 US Food and Drug Administration
357(3)
10.3.2 International regulatory guidance
360(1)
10.3.2.1 European Union
360(1)
10.3.2.2 International Conference on Harmonization
361(2)
10.3.2.3 The World Health Organization
363(1)
10.4 Regulatory approaches relevant to data monitoring committee operation: the US FDA
364(3)
10.5 Policies of funding agencies regarding DMC operations
367(1)
10.5.1 National Institutes of Health
367(2)
10.5.2 Other federal agencies
369(1)
10.5.3 Funding agencies outside the US
369(1)
10.6 Involvement of FDA staff in data monitoring committee deliberations
370(2)
10.7 Examples of regulatory authority interaction with data monitoring committees
372(7)
References
379(4)
11 Legal Considerations for DMCs
383(28)
11.1 DMC indemnification
383(17)
11.1.1 Motivating examples
385(3)
11.1.2 Emergence of DMCs and heightened awareness of their existence
388(2)
11.1.3 Further motivation for indemnification to protect the DMC
390(2)
11.1.4 Some specific concerns from current experiences with indemnification
392(2)
11.1.5 Potential solutions to indemnification issues
394(3)
11.1.6 Confidential disclosure agreement (CDA)
397(2)
11.1.7 Summary of indemnification, liability, and contracting issues
399(1)
11.2 Balancing legal and ethical responsibilities: a need for a mediator?
400(6)
11.2.1 A case study: the setting of Actimmune in patients with idiopathic pulmonary fibrosis
402(3)
11.2.2 IMMUNE response AIDS clinical trial
405(1)
References
406(5)
Appendix A The Data Monitoring Committee Charter 411(20)
Appendix B Performance Standards Document 431(20)
Statistics in Practice 451(4)
Index 455
SUSAN S. ELLENBERG, PHD, is Professor of Biostatistics, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, USA.

THOMAS R. FLEMING, PHD, is Professor of Biostatistics and Statistics, Department of Biostatistics, School of Public Health, University of Washington, USA.

DAVID L. DEMETS, PHD, is Professor Emeritus and Founding Chair of the Department of Biostatistics and Medical Informatics, University of Wisconsin–Madison, USA.