Schneider Lon S, Goldberg Terry E
USC Keck School of Medicine Los Angeles California.
Department of Psychiatry Columbia University Medical Center New York New York.
Alzheimers Dement (Amst). 2020 May 15;12(1):e12017. doi: 10.1002/dad2.12017. eCollection 2020.
Composite scales have been advanced as primary outcomes in early stage Alzheimer's disease trials, and endorsed by the U.S. Food and Drug Administration (FDA) for pivotal trials. They are generally composed of several neurocognitive subscales and may include clinical and functional activity scales.
We summarized the development of 12 composite scales intended as outcomes for clinical trials and assessed their characteristics.
Composite scales have been constructed from past observational and clinical trial databases by selecting components of individual neuropsychological tests previously used in clinical trials. The atheoretical approaches to combining scales into a composite scale that have often been used risk omitting clinically important measures and so may include redundant, irrelevant, or noncontributory tests. The deliberate combining of neurocognitive scales with functional activity scales provides arbitrary weightings that also may be clinically irrelevant or obscure change in a particular domain. Basic psychometric information is lacking for most of the composites.
Although composite scales are desirable for pivotal clinical trials because they, in principle, provide for a single, primary outcome combining neurocognitive and/or functional domains, they have substantial limitations, including their common derivations, inattention to basic psychometric principles, redundancy, absence of alternate forms, and, arguably, the inclusion of functional measures in some. In effect, any currently used composite is undergoing validation through its use in a trial. The assumption that a composite, by its construction alone, is more likely than an individual measure to detect an effect from any particular drug and that the effect is more clinically relevant or valid has not been demonstrated.
综合量表已被推荐作为早期阿尔茨海默病试验的主要结局指标，并得到了美国食品药品监督管理局（FDA）对关键试验的认可。它们通常由几个神经认知子量表组成，可能还包括临床和功能活动量表。
我们总结了12种旨在作为临床试验结局指标的综合量表的开发情况，并评估了它们的特征。
综合量表是通过从过去的观察性和临床试验数据库中选择先前在临床试验中使用的个体神经心理学测试的组成部分构建而成的。将量表组合成综合量表的无理论依据的方法经常被使用，这种方法有遗漏临床重要测量指标的风险，因此可能包括冗余、不相关或无贡献的测试。将神经认知量表与功能活动量表刻意组合会提供任意的权重，这在临床上也可能不相关或掩盖特定领域的变化。大多数综合量表缺乏基本的心理测量学信息。
尽管综合量表对于关键临床试验是可取的，因为原则上它们提供了一个将神经认知和/或功能领域结合起来的单一主要结局指标，但它们有很大的局限性，包括它们常见的推导方式、对基本心理测量学原则的忽视、冗余、缺乏替代形式，并且可以说，在一些量表中纳入了功能测量指标。实际上，任何当前使用的综合量表都在通过其在试验中的应用进行验证。仅通过其构建方式，综合量表就比单个测量指标更有可能检测到任何特定药物的效果，并且这种效果在临床上更相关或更有效的假设尚未得到证实。
