Clinical Trial Design Challenges in Mood Disorders

1st Edition - January 22, 2015
Editors: Mauricio Tohen, Charles Bowden, Andrew A. Nierenberg, John Geddes
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 4 0 5 1 7 0 - 6
eBook ISBN:
9 7 8 - 0 - 1 2 - 4 0 5 1 7 6 - 8

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 Di… Read more

Clinical Trial Design Challenges in Mood Disorders

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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.

List of Contributors
Preface
Chapter One. Clinical Trial Design of Maintenance Treatments in Bipolar Disorder
- Introduction
- Design of Maintenance Treatment Trials in Bipolar Disorder
- Definition of Outcome
- Conclusions
- References
Chapter Two. 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
Chapter Three. 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
Chapter Four. Long-Term Treatment of Mood Disorders: Follow-Up of Acute Treatment Phase Studies Versus Continuation and Maintenance Phase Studies, and Enriched Versus Non-Enriched Designs
- 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
Chapter Five. The Role of Noninferiority Designs in Bipolar Disorder Clinical Trials
- Introduction
- Trials for Drug Registration Versus Trials that are Most Clinically Informative
- Conclusions
- References
Chapter Six. 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
- Mixed Methods Research Defined
- Using Qualitative Methodologies in Clinical Trials
- An Example: N-Acetylcysteine in Schizophrenia
- Benefits and Limitations in Using Mixed Methods in Clinical Trials
- Conclusion
- Conflicts of Interest Statement
- References
Chapter Seven. 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 Randomization to Treatments for Developing or Persisting Clinically Significant Depression
- Synopsis of the 26-Week, Open, Randomized SMART Bipolar Disorder Study
- 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
Chapter Eight. Novel Study Designs for Clinical Trials in Mood Disorders
- Introduction
- Overcoming the Problem of Excessive Placebo Responses
- Standard Parallel Comparison Design
- Single-Blind Placebo Washout
- Crossover Design
- Adaptive Designs
- Sequential, Parallel Comparison Design
- An Example of Sequential, Parallel Comparison Design: L-Methylfolate as Adjunctive Therapy for Selective Serotonin Reuptake Inhibitor-Resistant Major Depression
- Pooled Response Rates
- Conclusions
- Dr. Maurizio Fava’s Lifetime Disclosures
- References
Chapter Nine. Rating Scales in Bipolar Disorder
- Introduction
- Screening Instruments for Bipolar Disorder
- Mania Scales
- Depression Scales in Bipolar Disorder
- Other Relevant Dimensions of Bipolar Outcome in Clinical Trials
- Rating Scales in Bipolar Populations Across the Lifespan
- Future Directions in Applications of Rating Scales in Bipolar Clinical Trials
- References
Chapter Ten. 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
- Industry-Driven Versus Investigator-Driven Trials in General
- Generalizability and Clinical Applicability of Trial Results in Bipolar Disorder
- Summarizing and Concluding Sections
- References
Chapter Eleven. 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
- Discussion: Developments in India
- Concluding Notes
- References
Index

Mauricio Tohen

Mauricio Tohen, MD, DrPH, MBA is the Chairman of the Department of Psychiatry at the University of New Mexico Health Sciences Center in Albuquerque NM, USA.

Dr Tohen was born and raised in Mexico City. He earned his medical degree from the National University of Mexico and his Doctorate in Public Health (Epidemiology) from Harvard University. His postdoctoral training included a residency in Psychiatry at the University of Toronto and a fellowship at McLean Hospital, Harvard Medical School. Dr Tohen also obtained an MBA degree from the Indiana University Kelly School of Business.

Dr Tohen was the Clinical Director of the Bipolar and Psychotic Disorders Program at McLean Hospital (1988-1997). In 1997 he joined Lilly Research Laboratories where he reached the senior most scientific rank of Distinguished Lilly Scholar. From 2009-2013 he was the Head of the Division of Mood & Anxiety Disorders and the Krus Endowed Tenured Professor in Psychiatry at the University of Texas Health Science Centre at San Antonio.

Among numerous awards, Dr Tohen received a National Service Award in Psychiatric Epidemiology from the National Institute of Mental Health (NIMH) and Harvard University. He also received a FIRST award from NIMH, the Pope Award from McLean Hospital, a NARSAD Young Investigator Award and in 2011 the Simon Bolivar Award from the American Psychiatric Association for outstanding contribution to education, research and overall achievement in Psychiatry and leadership in Hispanic Psychiatry. From 2010 to 2012, Dr Tohen was the President of the International Society for Bipolar Disorders. He is the President of the American Society of Hispanic Psychiatry (2014-2016).

Dr Tohen's research, supported by grants from NIMH, private foundations and the pharmaceutical industry, has focused on the epidemiology, outcome, and treatment of Bipolar and Psychotic Disorders. He has authored more than 250 original publications and edited or co-edited four books including Mood Disorders Across the Life Span (1996), Comorbidity in Affective Disorders (1999), Bipolar Disorder: The Upswing in Research and Treatment (2005), Bipolar Psychopharmacotherapy (first edition 2006, second edition 2011), and Psychiatric Epidemiology (first edition 1995, second edition 2003, third edition 2011).

In 2014 he was in the top 100 most cited researchers worldwide for the last decade in the field of Psychiatry and Psychology and selected as a Thomson Reuters Highly cited researcher and also in the 2014 list of World’s Most influential Scientific Minds.

Affiliations and expertise

Department of Psychiatry and Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

Charles Bowden

Affiliations and expertise

Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA

Andrew A. Nierenberg

Affiliations and expertise

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

John Geddes

Affiliations and expertise

Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK