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How Commonly Used Inclusion and Exclusion Criteria in Antidepressant Registration Trials Affect Study Enrollment

PRESKORN, SHELDON H. MD; MACALUSO, MATTHEW DO; TRIVEDI, MADHUKAR MD

Journal of Psychiatric Practice: July 2015 - Volume 21 - Issue 4 - p 267–274
doi: 10.1097/PRA.0000000000000082
Articles

In clinical trials, each specific inclusion and exclusion criterion eliminates a percentage of the potentially eligible population from trial participation and thus increases the time and effort needed for enrollment in a study. Drug developers often do not have data on how these criteria affect the pool of potentially eligible subjects for their trials and, hence, they cannot factor in the impact of these criteria when designing a study and planning the time needed to complete it. Consequently, drug developers often have ambitious timelines that are unrealistic and can lead to actions that may interfere with the ability to separate the efficacy of drug versus placebo. To investigate the effects of inclusion and exclusion criteria on study enrollment, the authors quantified the effects of the inclusion and exclusion criteria commonly used in antidepressant registration trials (ARTs) by applying these criteria to the population treated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. In essence, the STAR*D study population was used as a surrogate for the general population of individuals with major depressive disorder. The effect of each criterion commonly used in ARTs was assessed in terms of the percentage of the STAR*D population that would have been excluded individually and collectively (ie, when all criteria were applied at once). For continuous criteria such as age and severity of depression, the resulting effects have been presented graphically. Collectively, the typical inclusion and exclusion criteria used in ARTs would have eliminated at least 82% of the STAR*D population. This result means that more than 5 times the number of subjects would have to be screened to find a population that would meet the typical inclusion and exclusion criteria for an ART, directly determining the screening effort required in terms of both resources and time. Thus, developers of antidepressant drugs can use the data from this study to plan the recruitment effort required and to weigh any potential benefit of each criterion alone and in aggregate versus their cost in terms of recruitment support and time. These data also graphically illustrate for prescribers how restrictive the population likely to be enrolled in ARTs is relative to the patients whom they treat with such medications.

PRESKORN and MACALUSO: University of Kansas School of Medicine-Wichita, Wichita, KS

TRIVEDI: University of Texas Southwestern Medical Center, Dallas, TX

S.H.P. is Professor in Psychiatry and Behavioral Sciences at the University of Kansas School of Medicine-Wichita and Professor of Psychiatry, Laureate Institute for Brain Research, Tulsa, OK. M.M. is Assistant Professor, Director of Residency Training, and Director of Research in Psychiatry and Behavioral Sciences at the University of Kansas School of Medicine-Wichita, Wichita, KS. M.T. is Professor of Psychiatry, Department of Psychiatry, at the University of Texas Southwestern Medical School, Dallas, TX.

Poster presented at the 53rd Annual New Clinical Drug Evaluation Unit (NCDEU) meeting, May 28–31, 2013, Hollywood, FL, sponsored by the American Society of Clinical Pharmacology.

Over his career, S.H.P. has worked with over 125 pharmaceutical companies in the United States and throughout the world. Over the past year, S.H.P. has received grants/research support from or has served as a consultant, on the advisory board, or on the speakers bureau for Assurex Health, Cambridge Isotope Laboratories, Cubist/Trius, Eisai, EnViVo, GlaxoSmithKline, Forum, Johnson & Johnson, Merck, Naurex, National Institute of Mental Health, Pfizer, Stanley Medical Research Institute, and Sunovion. M.M. has conducted clinical trials research as principal investigator for the following pharmaceutical companies over the past 12 months: AbbVie, Alkermes, Assurex, Eisai, Forum, and Naurex. In the case of both S.H.P. and M.M., all clinical trial and study contracts were with and payments made to the Kansas University Medical Center Research Institute, a research institute affiliated with Kansas University School of Medicine-Wichita (KUSM-W). M.T. is or has been an advisor/consultant and received fees from Abbott Laboratories, Abdi Ibrahim, Akzo (Organon Pharmaceuticals), Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb, Cephalon, Cerecor, CME Institute of Physicians, Concert Pharmaceuticals, Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Global Services, Janssen Pharmaceutica Products, Johnson & Johnson, Libby, Lundbeck, Meade Johnson, MedAvante, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America, Naurex, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Pfizer, PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products Ltd, Sepracor, SHIRE Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories. He also received grants/research support from the Agency for Healthcare Research and Quality (AHRQ), Corcept Therapeutics, Cyberonics, Merck, the National Alliance for Research in Schizophrenia and Depression, the National Institute of Mental Health, and the National Institute on Drug Abuse.

Please send correspondence to: Matthew Macaluso, DO, University of Kansas School of Medicine-Wichita, 1010 North Kansas, Wichita, KS, 67204 (e-mail: mmacaluso@kumc.edu).

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