title: Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations. Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials.
abstract: The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from study participants have made the consideration of multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes can limit the validity and utility of clinical trials; specifying multiple endpoints for the evaluation of treatment efficacy, however, can increase the rate of false positive conclusions about the efficacy of a treatment. We describe the use of multiple endpoints in the design, analysis, and interpretation of pain clinical trials, and review available strategies and methods for addressing multiplicity. To decrease the probability of a Type I error (i.e., the likelihood of obtaining statistically significant results by chance) in pain clinical trials, the use of gatekeeping procedures and other methods that correct for multiple analyses is recommended when a single primary endpoint does not adequately reflect the overall benefits of treatment. We emphasize the importance of specifying in advance the outcomes and clinical decision rule that will serve as the basis for determining that a treatment is efficacious and the methods that will be used to control the overall Type I error rate.
authors.affiliation: Department of Anesthesiology, University of Washington, P.O. Box 356540, Seattle, WA 98195, USA Department of Anesthesiology, University of Rochester, Rochester, NY, USA Mayne Medical School, University of Queensland, Brisbane, Queensland, Australia United States Food and Drug Administration, Silver Spring, MD, USA Epidemiology, Merck & Co., Blue Bell, PA, USA Department of Symptom Relief, MD Anderson Cancer Center American Chronic Pain Association, Rocklin, CA, USA Clinical Research, Allergan, Inc., Irvine, CA, USA Center for Clinical Epidemiology & Biostatistics, University of Pennsylvania, Philadelphia, PA, USA Lilly Corporate Center, Eli Lilly & Co, Indianapolis, IN, USA Center for Global Health, University of Toronto, Toronto, Ontario, Canada Schwarz Biosciences, Research Triangle Park, NC, USA NeurogesX, Inc., San Carlos, CA, USA Analgesic Research, Needham, MA, USA Celgene Corporation, Summit, NJ, USA Pfizer, Inc., Ann Arbor, MI, USA Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA Department of Psychology, Dalhousie University, Canada Pain Relief, Oxford University, Oxford, UK GlaxoSmithKline, Research Triangle Park, NC, USA United Biosource Corporation, Bethesda, MD, USA Johnson & Johnson, Raritan, NJ, USA Alpharma, Piscataway, NJ, USA AstraZeneca R&D, Sodertalje, Sweden Endo Pharmaceuticals Inc, Chadds Ford, PA USA United States Food and Drug Administration, now at United States National Institutes of Health, USA.
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mesh_terms: D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D015986:Confounding Factors, Epidemiologic; D023381:Endpoint Determination / Q000706:statistics & numerical data*; D006801:Humans; D016018:Least-Squares Analysis; D015999:Multivariate Analysis; D059408:Pain Management; D011338:Probability Theory; D012107:Research Design / Q000706:statistics & numerical data