title: Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations.
abstract: A number of pharmacologic treatments examined in recent randomized clinical trials (RCTs) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated. Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies, such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ("assay sensitivity"). Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development. Therefore, an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was reviewed and discussed. On the basis of this meeting and subsequent discussions, the authors recommend consideration of a number of patient, study design, study site, and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments. Increased attention to and research on methodological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence-based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety.
authors.affiliation: Departments of Anesthesiology and Neurology and Center for Human Experimental Therapeutics, University of Rochester, Rochester, NY 14642, USA University of Washington, Seattle, WA, USA University of Rochester, Rochester, NY, USA United States Food and Drug Administration, Silver Spring, MD, USA University of Pennsylvania, Philadelphia, PA, USA Queen's University, Kingston, ON, Canada Analgesic Solutions, Natick, MA, USA Tufts University, Boston, MA, USA Johns Hopkins University, Baltimore, MD, USA California Pacific Medical Center Research Institute, San Francisco, CA, USA University of Wisconsin, Madison, WI, USA University of Kiel, Kiel, Germany University of Queensland, Brisbane, Australia Bristol-Myers Squibb, Wallingford, CT, USA American Chronic Pain Association, Rocklin, CA, USA DePuy Spine, Raynham, MA, USA Pfizer, New London, CT, USA Eisai Limited, Mosquito Way, Hatfield, UK Department of Veterans Affairs, West Haven, CT, USA Yale University, New Haven, CT, USA Nuvo Research, West Chester, PA, USA Endo Pharmaceuticals Inc., Chadds Ford, PA, USA Durect Corporation, Cupertino, CA, USA AstraZeneca, Wilmington, DE, USA Purdue Pharma, Stamford, CT, USA National Institutes of Health, Bethesda, MD, USA Johnson & Johnson Pharmaceutical Research & Development, Titusville, NJ, USA Imperial College, London, UK Faculdade de Medicina de Lisboa, Lisbon, Portugal Eli Lilly & Co., Indianapolis, IN, USA King Pharmaceuticals (currently Pfizer), Cary, NC, USA Oregon Health and Science University, Portland, OR, USA Grünenthal GmbH, Aachen, Germany NeurogesX, Inc., San Carlos, CA, USA Harvard Medical School, Boston, MA, USA University of Ottawa, Ottawa, ON, Canada Smith & Nephew, Durham, NC, USA German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany.
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mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D006801:Humans; D059408:Pain Management / Q000379:methods / Q000592:standards; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000592:standards*
chemical_list: D000700:Analgesics