Turk Dennis C, Dworkin Robert H, McDermott Michael P, Bellamy Nicholas, Burke Laurie B, Chandler Julie M, Cleeland Charles S, Cowan Penney, Dimitrova Rozalina, Farrar John T, Hertz Sharon, Heyse Joseph F, Iyengar Smriti, Jadad Alejandro R, Jay Gary W, Jermano John A, Katz Nathaniel P, Manning Donald C, Martin Susan, Max Mitchell B, McGrath Patrick, McQuay Henry J, Quessy Steve, Rappaport Bob A, Revicki Dennis A, Rothman Margaret, Stauffer Joseph W, Svensson Ola, White Richard E, Witter James
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.
Pain. 2008 Oct 31;139(3):485-493. doi: 10.1016/j.pain.2008.06.025. Epub 2008 Aug 15.
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.
随机临床试验日益复杂，且要从研究参与者那里获取各种各样的测量数据，这使得在临床试验的设计、分析和解释中考虑多个终点成为一个极其重要的问题。不考虑重要结果会限制临床试验的有效性和实用性；然而，为评估治疗效果指定多个终点可能会增加关于治疗效果的假阳性结论的发生率。我们描述了在疼痛临床试验的设计、分析和解释中使用多个终点的情况，并回顾了处理多重性的可用策略和方法。为降低疼痛临床试验中I型错误（即偶然获得具有统计学意义结果的可能性）的概率，当单一主要终点不能充分反映治疗的总体益处时，建议使用把关程序和其他校正多重分析的方法。我们强调预先指定将作为确定治疗有效的基础的结果和临床决策规则以及将用于控制总体I型错误率的方法的重要性。
