Tohen / Bowden / Nierenberg Clinical Trial Design Challenges in Mood Disorders

1. Auflage 2015
ISBN: 978-0-12-405176-8
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 192 Seiten

Poor clinical trial designs result in failed studies wasting research funds and limiting the advancement of cures for disorders. Clinical Trial Design Challenges in Mood Disorders outlines classic problems researchers face in designing clinical trials and discusses how best to address them for the most definitive and generalizable results. Traditional trial designs are included as well as novel analytic techniques. The book examines information on high placebo response, the generalizability of studies conducted in the developing world, the duration of maintenance studies, and the application of findings into clinical practice. With representation from contributors throughout the world and from academia, industry, regulatory agencies, and advocacy groups, this book will contribute toward improved clinical trial design and valid, precise, and reliable answers about what works better and faster for patients. - Summarizes common trial design problems and their solutions - Encompasses funding, subject selection, regulatory issues and more - Identifies best practices for definitive and generalizable results - Includes traditional trial designs and novel analytic techniques - Represents academia, industry, regulatory agencies, and advocacy groups

Autoren/Hrsg.

Tohen, Mauricio

Bowden, Charles

Nierenberg, Andrew A.

Geddes, John

Inhaltsverzeichnis

1;Front Cover;1
2;Clinical Trial Design Challenges in Mood Disorders;4
3;Copyright Page;5
4;Contents;6
5;List of Contributors;10
6;Preface;12
7;1 Clinical Trial Design of Maintenance Treatments in Bipolar Disorder;14
7.1;Introduction;14
7.2;Design of Maintenance Treatment Trials in Bipolar Disorder;15
7.2.1;Need for a Uniform Nomenclature of Course and Outcome in Bipolar Disorders;15
7.2.2;Trial Duration;16
7.3;Definition of Outcome;18
7.3.1;Placebo-Controlled Maintenance Studies in Bipolar Disorder;18
7.3.2;Patient Recruitment;19
7.3.2.1;Course of Illness;19
7.3.3;Symptoms Ratings;20
7.3.4;Statistical Considerations;20
7.3.5;Regulatory Considerations;22
7.4;Conclusions;23
7.5;References;23
8;2 Meta-Analysis of Clinical Trials in Bipolar Disorder;26
8.1;Introduction;26
8.2;Reduction of Risk of Suicide With Lithium: An Example of Increased Statistical Power by Pooling;27
8.3;Publication Bias;29
8.4;Individual Patient Data Meta-Analyses;30
8.5;Multiple Treatments Meta-Analysis;32
8.6;Conclusions;34
8.7;References;34
9;3 Effectiveness Trials in Bipolar Disorders;36
9.1;Efficacy Versus Effectiveness: Two Words With the Same But Different Meanings;36
9.2;General Considerations;37
9.3;Systematic Treatment Enhancement Program for Bipolar Disorder;37
9.4;Bipolar Affective Disorder: Lithium/Anticonvulsant Evaluation Trial;38
9.5;Danish University Antidepressant Group Study 6;39
9.6;Lithium Moderate Dose Use Study;39
9.7;Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness Trial;39
9.8;Conclusions;40
9.9;References;40
10;4 Long-Term Treatment of Mood Disorders: Follow-Up of Acute Treatment Phase Studies Versus Continuation and Maintenance ...;42
10.1;Introduction;43
10.2;Requirements for Licensing Drugs in Mood Disorders;43
10.3;Long-Term Follow-Up of Randomized (Placebo-)Controlled Acute Treatment Studies;45
10.4;Randomized (Placebo-)Controlled Continuation Phase Withdrawal Studies;49
10.5;Randomized (Placebo-)Controlled Maintenance Phase Withdrawal Studies;52
10.6;Enriched Versus Nonenriched Designs;54
10.7;Conclusion;58
10.8;References;59
11;5 The Role of Noninferiority Designs in Bipolar Disorder Clinical Trials;62
11.1;Introduction;62
11.2;Trials for Drug Registration Versus Trials that are Most Clinically Informative;64
11.2.1;Why Superiority Designs are Preferred by Regulators in the Field of Bipolar Disorder;64
11.2.2;The Need of Clinically Informative Designs: Alternatives to Superiority Observational and Exploratory Trials;64
11.2.2.1;Noninferiority Designs;65
11.3;Conclusions;68
11.4;References;68
12;6 The Use of Mixed Methods in Drug Discovery: Integrating Qualitative Methods into Clinical Trials;72
12.1;Introduction;73
12.2;A Rationale for Mixed-Method Approaches to Clinical Trial Design;73
12.3;Qualitative Research Defined;74
12.4;Theoretical Perspectives in Qualitative Research;75
12.4.1;Ethnography;75
12.4.2;Phenomenology;76
12.4.3;Postmodernism;76
12.4.4;Hermeneutics;76
12.4.5;Middle-Range Theories;77
12.5;Mixed Methods Research Defined;78
12.6;Using Qualitative Methodologies in Clinical Trials;78
12.6.1;Research Strategy;79
12.6.2;Research Methods;79
12.6.3;Sampling and Analysis;80
12.6.4;Other Materials and Methods;81
12.7;An Example: N-Acetylcysteine in Schizophrenia;82
12.8;Benefits and Limitations in Using Mixed Methods in Clinical Trials;84
12.9;Conclusion;85
12.10;Conflicts of Interest Statement;85
12.11;References;86
13;7 Sequential Multiple Assignment Randomized Treatment (SMART): Designs in Bipolar Disorder Clinical Trials;88
13.1;Introduction;89
13.2;SMART Methodologies;90
13.3;SMART Study of Primary Lithium or Valproate in Clinically Symptomatic Bipolar Disorder Coupled with Second-Phase Randomizat ...;91
13.4;Synopsis of the 26-Week, Open, Randomized SMART Bipolar Disorder Study;92
13.4.1;Participants;92
13.4.2;Study Summary;92
13.4.3;Induction Phase;92
13.4.4;Maintenance Phase;92
13.4.5;Disposition of Subjects and Sample Size of Groups;93
13.4.6;Medications;93
13.4.7;Assessments;94
13.4.8;Criteria for Recovered Status;94
13.4.9;Hypothesis: A.2.1;94
13.4.10;Hypothesis A.3.1;95
13.4.11;Hypothesis A.2.2;95
13.4.12;Hypothesis A.2.3;95
13.4.13;Exploratory Analyses and Qualitative Aim 1;95
13.4.14;Power Analyses;96
13.4.15;Innovation and Significance;96
13.4.15.1;Approach and Feasibility;96
13.5;Consideration in Planning and Executing SMART Protocols;96
13.6;Selective Review of SMART Studies in Other Areas of Medicine;97
13.7;Prospective Design Considerations for SMART Studies;98
13.8;Matching the Statistical Analysis to the Rationale for a SMART;98
13.9;References;99
14;8 Novel Study Designs for Clinical Trials in Mood Disorders;100
14.1;Introduction;101
14.2;Overcoming the Problem of Excessive Placebo Responses;102
14.2.1;Standardizing Diagnostic Procedures;102
14.2.2;Restricting Enrollment to Selected Populations;103
14.2.3;Managing Clinicians’ Overestimation of Change;103
14.2.4;Rater Training;103
14.2.5;Requirement of Same Rater;104
14.2.6;Simplification of Study Visits and Assessments;104
14.2.7;Minimizing Nonspecific, Therapeutic Effects;104
14.2.8;Placebo Lead-in Phases;105
14.2.9;Extending Trial Duration;105
14.2.10;Reducing Number of Sites;105
14.2.11;Increasing the Sensitivity of Outcome Measures;106
14.2.12;Reducing the Number of Treatment Arms;106
14.3;Standard Parallel Comparison Design;106
14.4;Single-Blind Placebo Washout;107
14.5;Crossover Design;108
14.6;Adaptive Designs;109
14.6.1;Randomized Play-the-Winner Clinical Trials;109
14.6.2;Progressive Elimination of High Placebo Response Sites;110
14.7;Sequential, Parallel Comparison Design;111
14.8;An Example of Sequential, Parallel Comparison Design: L-Methylfolate as Adjunctive Therapy for Selective Serotonin Reuptake ...;113
14.8.1;Trial One;114
14.8.2;Trial Two;114
14.9;Pooled Response Rates;115
14.10;Conclusions;115
14.11;Dr. Maurizio Fava’s Lifetime Disclosures;115
14.12;References;116
15;9 Rating Scales in Bipolar Disorder;118
15.1;Introduction;119
15.2;Screening Instruments for Bipolar Disorder;120
15.2.1;General Behavioral Inventory;120
15.2.2;Manic Depressiveness Scale;120
15.2.3;Mood Disorder Questionnaire;120
15.2.4;Bipolar Affective Disorder Dimensional Scale;120
15.2.5;Bipolar Spectrum Diagnostic Scale;121
15.2.6;Screening Assessment of Depression-Polarity;121
15.3;Mania Scales;121
15.3.1;Review of Instruments;121
15.3.2;Description of Specific Instruments;121
15.3.2.1;Rater-Administered Mania Scales;121
15.3.2.1.1;Manic State Rating Scale;121
15.3.2.1.2;Modified Manic Rating Scale;122
15.3.2.1.3;Petterson Scale;122
15.3.2.1.4;Young Mania Rating Scale;122
15.3.2.1.5;Bech-Rafaelsen Scale;123
15.3.2.1.6;Mania Rating Scale;123
15.3.2.1.7;Mania Diagnostic and Severity Scale;123
15.3.2.1.8;Clinician Administered Rating Scale for Mania;123
15.3.2.1.9;Clinical Global Impression-Bipolar;124
15.3.2.2;Patient-Rated Mania Scales;124
15.3.2.2.1;Visual Analog Scales;124
15.3.2.2.2;M-D Scale;125
15.3.2.2.3;Self-Report Mania Inventory;125
15.3.2.2.4;Affective Self-Rating Scale;125
15.3.2.2.5;Altman Self-Report Mania Rating Scale;125
15.3.2.3;Mania Scales in Clinical Trials and Related Literature;125
15.4;Depression Scales in Bipolar Disorder;127
15.4.1;Review of Instruments;127
15.4.2;Description of Specific Instruments for Measuring Depressive Symptoms in Bipolar Disorder;128
15.4.2.1;Rater-Administered Depression Scales Used in Bipolar Studies;128
15.4.2.1.1;Hamilton Rating Scale for Depression;128
15.4.2.1.2;Montgomery Äsberg Depression Rating Scale;129
15.4.2.1.3;Inventory of Depressive Symptomatology;129
15.4.2.1.4;Bipolar Depression Rating Scale;130
15.4.2.2;Patient-Rated Depression Scales Used in Bipolar Studies;130
15.4.2.2.1;Quick Inventory of Depressive Symptomatology;130
15.4.2.2.2;Beck Depression Inventory;131
15.4.3;Depression Scales in Clinical Trials and Related Literature;131
15.5;Other Relevant Dimensions of Bipolar Outcome in Clinical Trials;131
15.5.1;Bipolar Response using Rating Scales;134
15.5.2;Bipolar Remission using Rating Scales;134
15.5.3;Bipolar Relapse, Recurrence, and Recovery using Rating Scales;134
15.5.4;Rating Scales to Assess Other Important Dimensions of Clinical Outcome among Bipolar Patients in Clinical Trials;137
15.6;Rating Scales in Bipolar Populations Across the Lifespan;138
15.6.1;Older Individuals with Bipolar Disorder;138
15.6.2;Children with Bipolar Disorder;139
15.7;Future Directions in Applications of Rating Scales in Bipolar Clinical Trials;140
15.8;References;141
16;10 Clinical Applicability of Results from Drug Trials in Bipolar Disorder – An Attempt to Shed Light on a Complex Issue;150
16.1;Introducing the Problem;151
16.2;Aims and Methods;152
16.3;Conceptual Framework;153
16.3.1;Unfolding the Basic Concepts;153
16.3.2;Selection of Subjects to Randomized Clinical Trials;154
16.3.3;Narrow Versus Broad Generalizability;156
16.3.4;Effect Size and Clinical Applicability of Trial Results;156
16.3.5;Generalizability Across Classification Systems;157
16.3.6;Generalizability Across Age;158
16.3.7;Generalizability Across Drugs;158
16.3.8;Generalizability and Adverse Effects;159
16.4;Industry-Driven Versus Investigator-Driven Trials in General;159
16.5;Generalizability and Clinical Applicability of Trial Results in Bipolar Disorder;160
16.5.1;Mania;160
16.5.2;Bipolar Depression;162
16.5.3;Mixed States;165
16.5.4;Maintenance;165
16.5.5;Differential Generalizability or Trial Results Based on Biologic Subgroups in Bipolar Disorder;169
16.6;Summarizing and Concluding Sections;170
16.6.1;Proper Clinical Applicability of Trial Results in Bipolar Disorder: A Brief Guidance;170
16.6.2;From Narrow Generalizability to Broad Applicability: Summarizing the Clinician’s Point of View;171
16.6.3;Approval Trials, Clinical Needs, and Future Perspectives;172
16.7;References;173
17;11 Clinical Trials in Developing Countries: Challenges in Design, Execution, and Regulation;180
17.1;Introduction;180
17.2;Clinical Trials in Developing Countries: Who Gains, and Why?;181
17.3;Clinical Trials in Developing Countries: Who Loses, and Why?;182
17.4;The Regulatory Environment;184
17.4.1;Special Issues;184
17.5;Discussion: Developments in India;185
17.6;Concluding Notes;186
17.7;References;186
18;Index;188