A crucial aspect of any clinical trial is using the right outcome measure to assess treatment efficacy. Compared to the rapidly evolved understanding and measurement of pathophysiology in preclinical and early symptomatic stages of Alzheimer's disease (AD), relatively less progress has been made in the evolution of clinical outcome assessments (COAs) for those stages. The current paper aims to provide a benchmark for the design and evaluation of COAs for use in early AD trials. We discuss lessons learned on capturing cognitive changes in predementia stages of AD, including challenges when validating novel COAs for those early stages and necessary evidence for their implementation in clinical trials. Moving forward, we propose a multi-step framework to advance the use of more effective COAs to assess clinically meaningful changes in early AD, which will hopefully contribute to the much-needed consensus around more appropriate outcome measures to assess clinical efficacy of putative treatments.

中文翻译：

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为什么临床试验与其结果测量一样好：阿尔茨海默病临床试验认知结果测量的选择和使用框架


任何临床试验的一个重要方面是使用正确的结果测量来评估治疗效果。与阿尔茨海默病（AD）临床前和早期症状阶段病理生理学的快速发展的理解和测量相比，这些阶段的临床结果评估（COA）的进展相对较少。本文旨在为早期 AD 试验中使用的 COA 的设计和评估提供基准。我们讨论了捕捉 AD 痴呆前期阶段认知变化的经验教训，包括在早期阶段验证新型 COA 时面临的挑战以及在临床试验中实施其的必要证据。展望未来，我们提出了一个多步骤框架，以推进使用更有效的 COA 来评估早期 AD 中具有临床意义的变化，这有望有助于围绕更合适的结果指标达成急需的共识，以评估假定治疗的临床疗效。