Clinical Trial Design Challenges in Mood Disorders

Description

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. Front Cover Clinical Trial Design Challenges in Mood Disorders Copyright Page Contents List of Contributors Preface 1 Clinical Trial Design of Maintenance Treatments in Bipolar Disorder Introduction Design of Maintenance Treatment Trials in Bipolar Disorder Need for a Uniform Nomenclature of Course and Outcome in Bipolar Disorders Trial Duration Definition of Outcome Placebo-Controlled Maintenance Studies in Bipolar Disorder Patient Recruitment Course of Illness Symptoms Ratings Statistical Considerations Regulatory Considerations Conclusions References 2 Meta-Analysis of Clinical Trials in Bipolar Disorder Introduction Reduction of Risk of Suicide With Lithium: An Example of Increased Statistical Power by Pooling Publication Bias Individual Patient Data Meta-Analyses Multiple Treatments Meta-Analysis Conclusions References 3 Effectiveness Trials in Bipolar Disorders Efficacy Versus Effectiveness: Two Words With the Same But Different Meanings General Considerations Systematic Treatment Enhancement Program for Bipolar Disorder Bipolar Affective Disorder: Lithium/Anticonvulsant Evaluation Trial Danish University Antidepressant Group Study 6 Lithium Moderate Dose Use Study Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness Trial Conclusions References 4 Long-Term Treatment of Mood Disorders: Follow-Up of Acute Treatment Phase Studies Versus Continuation and Maintenance ... Introduction Requirements for Licensing Drugs in Mood Disorders Long-Term Follow-Up of Randomized (Placebo-)Controlled Acute Treatment Studies Randomized (Placebo-)Controlled Continuation Phase Withdrawal Studies Randomized (Placebo-)Controlled Maintenance Phase Withdrawal Studies Enriched Versus Nonenriched Designs Conclusion References 5 The Role of Noninferiority Designs in Bipolar Disorder Clinical Trials Introduction Trials for Drug Registration Versus Trials that are Most Clinically Informative Why Superiority Designs are Preferred by Regulators in the Field of Bipolar Disorder The Need of Clinically Informative Designs: Alternatives to Superiority Observational and Exploratory Trials Noninferiority Designs Conclusions References 6 The Use of Mixed Methods in Drug Discovery: Integrating Qualitative Methods into Clinical Trials Introduction A Rationale for Mixed-Method Approaches to Clinical Trial Design Qualitative Research Defined Theoretical Perspectives in Qualitative Research Ethnography Phenomenology Postmodernism Hermeneutics Middle-Range Theories Mixed Methods Research Defined Using Qualitative Methodologies in Clinical Trials Research Strategy Research Methods Sampling and Analysis Other Materials and Methods An Example: N-Acetylcysteine in Schizophrenia Benefits and Limitations in Using Mixed Methods in Clinical Trials Conclusion Conflicts of Interest Statement References 7 Sequential Multiple Assignment Randomized Treatment (SMART): Designs in Bipolar Disorder Clinical Trials Introduction SMART Methodologies SMART Study of Primary Lithium or Valproate in Clinically Symptomatic Bipolar Disorder Coupled with Second-Phase Randomizat ... Synopsis of the 26-Week, Open, Randomized SMART Bipolar Disorder Study Participants Study Summary Induction Phase Maintenance Phase Disposition of Subjects and Sample Size of Groups Medications Assessments Criteria for Recovered Status Hypothesis: A.2.1 Hypothesis A.3.1 Hypothesis A.2.2 Hypothesis A.2.3 Exploratory Analyses and Qualitative Aim 1 Power Analyses Innovation and Significance Approach and Feasibility Consideration in Planning and Executing SMART Protocols Selective Review of SMART Studies in Other Areas of Medicine Prospective Design Considerations for SMART Studies Matching the Statistical Analysis to the Rationale for a SMART References 8 Novel Study Designs for Clinical Trials in Mood Disorders Introduction Overcoming the Problem of Excessive Placebo Responses Standardizing Diagnostic Procedures Restricting Enrollment to Selected Populations Managing Clinicians’ Overestimation of Change Rater Training Requirement of Same Rater Simplification of Study Visits and Assessments Minimizing Nonspecific, Therapeutic Effects Placebo Lead-in Phases Extending Trial Duration Reducing Number of Sites Increasing the Sensitivity of Outcome Measures Reducing the Number of Treatment Arms Standard Parallel Comparison Design Single-Blind Placebo Washout Crossover Design Adaptive Designs Randomized Play-the-Winner Clinical Trials Progressive Elimination of High Placebo Response Sites Sequential, Parallel Comparison Design An Example of Sequential, Parallel Comparison Design: L-Methylfolate as Adjunctive Therapy for Selective Serotonin Reuptake ... Trial One Trial Two Pooled Response Rates Conclusions Dr. Maurizio Fava’s Lifetime Disclosures References 9 Rating Scales in Bipolar Disorder Introduction Screening Instruments for Bipolar Disorder General Behavioral Inventory Manic Depressiveness Scale Mood Disorder Questionnaire Bipolar Affective Disorder Dimensional Scale Bipolar Spectrum Diagnostic Scale Screening Assessment of Depression-Polarity Mania Scales Review of Instruments Description of Specific Instruments Rater-Administered Mania Scales Manic State Rating Scale Modified Manic Rating Scale Petterson Scale Young Mania Rating Scale Bech-Rafaelsen Scale Mania Rating Scale Mania Diagnostic and Severity Scale Clinician Administered Rating Scale for Mania Clinical Global Impression-Bipolar Patient-Rated Mania Scales Visual Analog Scales M-D Scale Self-Report Mania Inventory Affective Self-Rating Scale Altman Self-Report Mania Rating Scale Mania Scales in Clinical Trials and Related Literature Depression Scales in Bipolar Disorder Review of Instruments Description of Specific Instruments for Measuring Depressive Symptoms in Bipolar Disorder Rater-Administered Depression Scales Used in Bipolar Studies Hamilton Rating Scale for Depression Montgomery Äsberg Depression Rating Scale Inventory of Depressive Symptomatology Bipolar Depression Rating Scale Patient-Rated Depression Scales Used in Bipolar Studies Quick Inventory of Depressive Symptomatology Beck Depression Inventory Depression Scales in Clinical Trials and Related Literature Other Relevant Dimensions of Bipolar Outcome in Clinical Trials Bipolar Response using Rating Scales Bipolar Remission using Rating Scales Bipolar Relapse, Recurrence, and Recovery using Rating Scales Rating Scales to Assess Other Important Dimensions of Clinical Outcome among Bipolar Patients in Clinical Trials Rating Scales in Bipolar Populations Across the Lifespan Older Individuals with Bipolar Disorder Children with Bipolar Disorder Future Directions in Applications of Rating Scales in Bipolar Clinical Trials References 10 Clinical Applicability of Results from Drug Trials in Bipolar Disorder – An Attempt to Shed Light on a Complex Issue Introducing the Problem Aims and Methods Conceptual Framework Unfolding the Basic Concepts Selection of Subjects to Randomized Clinical Trials Narrow Versus Broad Generalizability Effect Size and Clinical Applicability of Trial Results Generalizability Across Classification Systems Generalizability Across Age Generalizability Across Drugs Generalizability and Adverse Effects Industry-Driven Versus Investigator-Driven Trials in General Generalizability and Clinical Applicability of Trial Results in Bipolar Disorder Mania Bipolar Depression Mixed States Maintenance Differential Generalizability or Trial Results Based on Biologic Subgroups in Bipolar Disorder Summarizing and Concluding Sections Proper Clinical Applicability of Trial Results in Bipolar Disorder: A Brief Guidance From Narrow Generalizability to Broad Applicability: Summarizing the Clinician’s Point of View Approval Trials, Clinical Needs, and Future Perspectives References 11 Clinical Trials in Developing Countries: Challenges in Design, Execution, and Regulation Introduction Clinical Trials in Developing Countries: Who Gains, and Why? Clinical Trials in Developing Countries: Who Loses, and Why? The Regulatory Environment Special Issues Discussion: Developments in India Concluding Notes References Index