The need to show minimum clinically important differences in Alzheimer's disease trials
The need to show minimum clinically important differences in Alzheimer's disease trials
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DOI：
10.1016/s2215-0366(21)00197-8
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发表时间：
2021-11-01
影响因子：
64.3
通讯作者：
Howard, Robert
中科院分区：
文献类型：
--
作者：
Liu, Kathy Y.;Schneider, Lon S.;Howard, Robert
确定构成临床有意义的治疗效果的结果中最小的变化(即最小临床重要差异[MCID])是解释临床试验结果、做出临床决策以及设计具有足够统计能力以检测任何此类影响的研究的基础。在阿尔茨海默病试验中，对于MCID的结果还没有达成共识，但美国食品和药物管理局(FDA)对阿杜卡努单抗临床试验数据的考虑暴露了统计上显著但微小改善的临床意义的不确定性。尽管包括阿尔茨海默病临床痴呆症评分和简易精神状态检查在内的结果的MCID已经有报道，但起草的食品和药物管理局指南没有具体说明量化的最小差异。尽管监管要求鼓励药物开发和批准是重要的，但如果没有MCID，赞助商的动机是支持试验，以检测对临床结果的微小和潜在无关紧要的影响的统计学意义。MCID有益于患者、家庭成员、照顾者和医疗保健系统，并应纳入阿尔茨海默病的临床试验和药物开发指南。
Deciding on the smallest change in an outcome that constitutes a clinically meaningful treatment effect (ie, the minimum clinically important difference [MCID]) is fundamental to interpreting clinical trial outcomes, making clinical decisions, and designing studies with sufficient statistical power to detect any such effect. There is no consensus on MCIDs for outcomes in Alzheimer's disease trials, but the US Food and Drug Administration's consideration of aducanumab clinical trials data has exposed the uncertainty of the clinical meaning of statistically significant but small improvements. Although MCIDs for outcomes, including Clinical Dementia Rating-Sum of Boxes and Mini-Mental State Examination in Alzheimer's disease have been reported, the Food and Drug Administration's guidelines, drafted in 1989 to facilitate regulatory approval of substantially effective antidementia drugs, do not specify quantified minimum differences. Although it is important that regulatory requirements encourage drug development and approval, without MCIDs, sponsors are motivated to power trials to detect statistical significance for only small and potentially inconsequential effects on clinical outcomes. MCIDs benefit patients, family members, caregivers, and health-care systems and should be incorporated into clinical trials and drug development guidance for Alzheimer's disease.