改善慢性疼痛临床试验中检测方法灵敏度的考虑因素：IMMPACT 建议。

Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations.

机构信息

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.

出版信息

Pain. 2012 Jun;153(6):1148-1158. doi: 10.1016/j.pain.2012.03.003. Epub 2012 Apr 9.

DOI:10.1016/j.pain.2012.03.003

PMID:22494920

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.

摘要

在一些先前已经证实有效的适应症中，许多在最近的随机临床试验（RCT）中被研究的药物治疗未能显示出与安慰剂相比具有统计学上的优越性。假设先前的疗效证据是有效的，并且这些研究中的患者和结果测量具有可比性，那么这些结果可能是这些 RCT 无法证明有效镇痛治疗与安慰剂相比的益处的能力的局限性所致（“检测灵敏度”）。努力提高镇痛试验的检测灵敏度可以降低对有效药物进行假阴性试验的频率，并提高镇痛药物开发的效率。因此，召开了一个关于临床试验中的方法、测量和疼痛评估的倡议会议，会上审查和讨论了慢性疼痛试验的检测灵敏度。基于这次会议和随后的讨论，作者建议考虑一些可能影响慢性疼痛治疗 RCT 检测灵敏度的患者、研究设计、研究地点和结果测量因素。更多地关注临床试验的方法学方面及其与检测灵敏度的关系，有可能为基于证据的镇痛临床试验设计方法提供基础，并加快发现具有更好疗效和安全性的镇痛治疗方法。