Adaptive and flexible clinical trials:
Saved in:
| Main Author: | |
|---|---|
| Format: | Book |
| Language: | English |
| Published: |
Boca Raton [u.a.]
CRC Press
2012
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | Includes bibliographical references and index |
| Physical Description: | XIII, 184 S. graph. Darst. 24 cm |
| ISBN: | 9781439838327 1439838321 |
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MARC
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| 245 | 1 | 0 | |a Adaptive and flexible clinical trials |c Richard Chin |
| 264 | 1 | |a Boca Raton [u.a.] |b CRC Press |c 2012 | |
| 300 | |a XIII, 184 S. |b graph. Darst. |c 24 cm | ||
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| 650 | 4 | |a Clinical Trials as Topic | |
| 650 | 4 | |a Database Management Systems |x trends | |
| 650 | 4 | |a Efficiency, Organizational | |
| 650 | 4 | |a Research Design | |
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Record in the Search Index
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| adam_text | Titel: Adaptive and flexible clinical trials
Autor: Chin, Richard
Jahr: 2012
Contents
Introduction..................................................................................,.........................xi
About the Author................................................................................................xiii
1. Background......................................................................................................1
1.1 Introduction...........................................................................................1
1.2 Definition and History of Traditional Clinical Trials......................2
1.3 Definition of Adaptive Clinical Trial..................................................5
1.4 Precursors to Modern Adaptive Clinical Trials..............................10
1.5 New Enabling Technologies and Other Requirements for
Adaptive Trials....................................................................................13
1.6 Rationale for Adaptive Clinical Trials.............................................14
1.7 Learn and Confirm.............................................................................16
1.8 Classification and Terminology of Adaptive Clinical Studies.....20
1.9 Non-Adaptive Study Designs............................................................ 21
1.10 Limitations of Adaptive Clinical Trials........................................... 21
1.11 Performance Criteria for Well-Designed Clinical Trials...............22
1.12 Evolving Regulatory Environment for Adaptive Clinical
Trials......................................................................................................27
1.13 Regulatory Guidance from the FDA................................................30
References.......................................................................................................36
2. Conventional Statistics................................................................................37
2.1 Basic Statistics......................................................................................37
2.2 Statistical Schools................................................................................37
2.3 Frequentist Method............................................................................38
2.4 Bayesian Method.................................................................................40
2.5 Likelihood Method.............................................................................40
2.6 Other Schools.......................................................................................41
2.7 Descriptive Statistics...........................................................................41
2.8 Inferential Statistics............................................................................41
2.9 Comparative Statistics........................................................................43
2.10 Hypothesis Testing.............................................................................44
2.11 Null Hypothesis and Standard of Proof in Clinical Trials...........44
2.12 Example of Inference and Hypothesis Testing...............................45
2.13 Statistical Tests and Choice of Statistical Test.................................47
2.14 Examples of Statistical Tests..............................................................48
2.15 Fundamental Statistical Assumptions.............................................50
2.15.1 Background.............................................................................50
2.15.2 Parametric Assumption........................................................52
vu
vjjj Contents
2.15.3 Continuity and Linearity Assumptions.............................53
2.15.4 Constant Hazard Ratio Assumptions.................................53
2.15.5 Independent and Random Sampling..................................53
2.15.6 Independence of Events........................................................54
3. Statistics Used in Adaptive Clinical Trials.............................................55
3.1 Introduction.........................................................................................55
3.2 Preserving the Alpha..........................................................................55
3.3 What Is Alpha?....................................................................................56
3.4 Misconception about p Values..........................................................58
3.5 Splitting the Alpha..............................................................................59
3.6 Methodologies for Allocating Alpha...............................................60
3.6.1 Bonferroni Correction...........................................................60
3.6.2 Holm Correction....................................................................61
3.6.3 Other Methods.......................................................................61
3.7 Evolution of Adaptive Analytic Methods: Interim Analysis........62
3.8 Adaptive Methods..............................................................................65
3.9 Limitations of Adaptive Statistical Techniques..............................69
3.10 Bayesian Approach.............................................................................71
3.11 Simulations and Modeling................................................................72
3.12 The FDA s Stance on Adaptive Techniques.....................................73
References.......................................................................................................93
4. Specific Requirements for Adaptive Trials.............................................95
4.1 Requirements for Endpoints in Adaptive Studies.........................95
4.2 Surrogates and Biomarkers...............................................................97
4.3 Practical Requirements......................................................................99
5. Adaptive Randomization and Allocation..............................................101
5.1 Traditional Fixed Allocation............................................................101
5.2 Simple Randomization.....................................................................102
5.3 Restricted and Blocked Randomization........................................102
5.4 Stratified, Nested, and Similar Randomization............................103
5.5 Balancing (Covariate) Adaptive Randomization..........................104
5.6 Response (Outcome) Adaptive Randomization...........................105
5.7 Combination and Multimodal Randomization............................106
5.8 Bayesian Randomization.................................................................107
5.9 Adaptation of Inclusion and Exclusion Criteria Based on
Blinded Data......................................................................................107
5.10 Patient Enrichment Adaptations.....................................................108
6. Sample Size Reestimation........................................................................Ill
6.1 Background........................................................................................111
6.2 , Sample Size Reestimation Based on Blinded Data.......................112
Contents ix
6.3 Sample Size Reestimation Based on Unblinded Data.................113
6.4 Adjustment in Follow-Up Time......................................................114
6.5 Internal Pilot Studies........................................................................114
6.6 Additional Rules...............................................................................115
References.....................................................................................................115
7. Traditional Dosing.....................................................................................117
7.1 Introduction.......................................................................................117
7.2 Definitions and Objectives of Dose Selection...............................118
7.3 Issues...................................................................................................119
7.4 Pharmacokinetics..............................................................................120
7.5 Factors Affecting Pharmacokinetics..............................................122
7.6 Dose-Response Curves....................................................................122
7.7 Types of Dosing.................................................................................123
7.7.1 Flat Doses..............................................................................123
7.7.2 Dosing Based on a Baseline Characteristic......................124
7.7.3 Titrated Dosing.....................................................................124
7.8 Traditional Dose-Escalation and Dose-Ranging Studies............124
8. Adaptive Dosing.........................................................................................129
8.1 Adaptive Dose Finding....................................................................129
8.2 Phase I Studies...................................................................................131
8.3 3 + 3 and Related Designs................................................................132
8.4 Continual Reassessment Method...................................................134
8.5 Dose Escalation with Overdose Control........................................137
8.6 Stochastic Approximation Methods...............................................138
8.7 Summary of Single-Parameter Models..........................................138
8.8 Additional Models and Methods....................................................139
8.9 Dose Adaptation in a Pivotal Study...............................................140
8.10 Changes in Concomitant Medications and Procedures..............141
References.....................................................................................................141
9. Interim Analysis and Adaptive Termination of Study and Study
Arms..............................................................................................................143
9.1 Overview............................................................................................143
9.2 Data and Safety Monitoring Boards...............................................143
9.3 Stopping Rules...................................................................................145
9.4 Individual Sequential Designs........................................................145
9.5 Group Sequential Designs...............................................................146
References.....................................................................................................147
10. Adaptive Changes in Study Design and Decision Rules...................149
10.1 Overview............................................................................................149
10.2 Changes to Follow-Up Period.........................................................149
Contents
10.3 Flexible Designs................................................................................149
10.4 Changing the Endpoints and Hypothesis.....................................150
10.4.1 Changes Based on Blinded Data.......................................150
10.4.2 Changes Based on Unblinded Data..................................150
10.5 Changes to Test Statistic or Analysis.............................................151
10.5.1 Changes Based on Blinded Data.......................................151
10.5.2 Changes Based on Unblinded Data..................................151
References.....................................................................................................152
11. Seamless Designs and Adaptive Clinical Trial Conduct...................155
11.1 Seamless Designs..............................................................................155
11.2 Challenges in Adaptive Trials.........................................................156
11.3 Maintaining the Blind......................................................................156
11.4 Infrastructure and Operations........................................................157
11.5 Adaptive Trial Protocols....................................,.............................159
12. Analysis and Interpretation of Results..................................................163
12.1 General Issues in Interpretation of Clinical Trial Results...........163
12.2 Interpretation of Adaptive Trial Results........................................169
12.3 Documentation of Trial Integrity....................................................170
12.4 Statistics of Adaptive Trial Analysis..............................................171
12.5 Summary............................................................................................172
References.....................................................................................................172
Index.....................................................................................................................173
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| spelling | Chin, Richard Verfasser (DE-588)136056407 aut Adaptive and flexible clinical trials Richard Chin Boca Raton [u.a.] CRC Press 2012 XIII, 184 S. graph. Darst. 24 cm txt rdacontent n rdamedia nc rdacarrier Includes bibliographical references and index Clinical trials Clinical Trials as Topic Database Management Systems trends Efficiency, Organizational Research Design HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025358373&sequence=000004&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Chin, Richard Adaptive and flexible clinical trials Clinical trials Clinical Trials as Topic Database Management Systems trends Efficiency, Organizational Research Design |
| title | Adaptive and flexible clinical trials |
| title_auth | Adaptive and flexible clinical trials |
| title_exact_search | Adaptive and flexible clinical trials |
| title_full | Adaptive and flexible clinical trials Richard Chin |
| title_fullStr | Adaptive and flexible clinical trials Richard Chin |
| title_full_unstemmed | Adaptive and flexible clinical trials Richard Chin |
| title_short | Adaptive and flexible clinical trials |
| title_sort | adaptive and flexible clinical trials |
| topic | Clinical trials Clinical Trials as Topic Database Management Systems trends Efficiency, Organizational Research Design |
| topic_facet | Clinical trials Clinical Trials as Topic Database Management Systems trends Efficiency, Organizational Research Design |
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