title: Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations.
abstract: There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions. An IMMPACT consensus meeting was therefore convened to identify the critical research design considerations for confirmatory chronic pain trials and to make recommendations for their conduct. We present recommendations for the major components of confirmatory chronic pain clinical trials, including participant selection, trial phases and duration, treatment groups and dosing regimens, and types of trials. Increased attention to and research on the methodological aspects of confirmatory chronic pain clinical trials has the potential to enhance their assay sensitivity and ultimately provide more meaningful evaluations of treatments for chronic pain.
authors.affiliation: Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642, USA University of Washington, Seattle, WA, USA University of Kiel, Kiel, Germany University of Queensland, Brisbane, Australia United States Food and Drug Administration, Silver Spring, MD, USA Eli Lilly & Co., Indianapolis, IN, USA United BioSource Corporation, Newtown, PA, USA M.D. Anderson Cancer Center, Houston, TX, USA American Chronic Pain Association, Rocklin, CA, USA Allergan, Inc, Irvine, CA, USA New York University, New York, NY, USA Queen's University, Kingston, Ontario, Canada University of Toronto, Toronto, Canada Schwarz Biosciences, Research Triangle Park, NC, USA AstraZeneca, Södertälje, Sweden Analgesic Research, Needham, MA, USA Department of Veterans Affairs, West Haven, CT, USA Celgene Corporation, Warren, NJ, USA University of Rochester, Rochester, NY, USA IWK Health Centre and Dalhousie University, Halifax, Nova Scotia, Canada Cephalon, Inc., Frazer, PA, USA National Institutes of Health, Bethesda, MD, USA qd consulting, LLC, Research Triangle Park, NC, USA Johnson & Johnson Pharmaceutical Research & Development LLC, Raritan, NJ, USA National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Merck & Company, Blue Bell, PA, USA Faculdade de Medicina de Lisboa, Lisbon, Portugal Mt. Sinai School of Medicine, New York, NY, USA Alpharma, Piscataway, NJ, USA University of Lucerne and Swiss Paraplegic Research, Lucerne, Switzerland NeurogesX, Inc., San Carlos, CA, USA Endo Pharmaceuticals Inc., Chadds Ford, PA, USA.
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authors.forename: Jarkko
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authors.lastname: Kalliomäki
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authors.lastname: Katz
authors.forename: Robert D
authors.initials: RD
authors.lastname: Kerns
authors.forename: Donald C
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authors.lastname: Manning
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDermott
authors.forename: Patrick J
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authors.forename: Arvind
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authors.lastname: Narayana
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authors.forename: Steve
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authors.lastname: Quessy
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authors.forename: Bryce B
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authors.forename: Cristina
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authors.lastname: Sampaio
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Stauffer
authors.forename: Gerold
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authors.lastname: Stucki
authors.forename: Jeffrey
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authors.forename: Richard E
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mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000592:standards; D010147:Pain Measurement / Q000379:methods / Q000592:standards; D010148:Intractable Pain / Q000188:drug therapy*; D018579:Patient Selection; D011897:Random Allocation; D012107:Research Design / Q000592:standards*
chemical_list: D000700:Analgesics