To understand the potential benefits of emerging Alzheimer's disease (AD) therapies within and beyond clinical trial settings, there is a need to advance current outcome measurements into meaningful information relevant to all stakeholders. The relationship between the impact on disease biology and clinically measurable outcomes in cognition, function, and behavior must be considered when defining the meaningful benefit of early AD therapies. In this review, we discuss: (1) the lack of consideration for biomarkers in the current concept of meaningfulness in AD; (2) the lack of gold standards for determining minimal biologically and clinically important differences (MBCIDs) in AD trials; (3) how the treatment benefits of disease‐modifying treatments are cumulative and increase over time; and (4) the different concepts of meaningfulness among key stakeholders. This review utilizes the future clinical biological framework of AD and aims to further integrate and expand the parameters of meaningful benefits toward a precision medicine framework.Highlights Definition of meaningful benefit from Alzheimer's disease (AD) treatment varies across disease stage and stakeholder perspectives. Observable and meaningful outcomes must consider the clinical‐biological nature of AD. Statistically significant effects or outcomes do not always equate to clinically meaningfulness. Assessment tools must reflect stage‐specific subtle changes following treatment. Real‐world evidence will support consensus, definition, and interpretation of clinical meaningfulness.

中文翻译：

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定义益处：下一代阿尔茨海默病临床护理路径的临床和生物学意义结果


为了了解新兴阿尔茨海默病 （AD） 疗法在临床试验环境内外的潜在益处，有必要将当前的结果测量推进为与所有利益相关者相关的有意义信息。在定义早期 AD 治疗的有意义益处时，必须考虑对疾病生物学的影响与认知、功能和行为的临床可测量结果之间的关系。在这篇综述中，我们讨论了：（1） 当前 AD 意义概念中缺乏对生物标志物的考虑;（2） 缺乏确定 AD 试验中最小生物学和临床重要差异 （MBCID） 的金标准;（3） 疾病缓解治疗的治疗益处如何累积并随着时间的推移而增加;（4） 主要利益相关者之间意义的不同概念。本综述利用 AD 的未来临床生物学框架，旨在进一步整合和扩展有意义益处的参数，以实现精准医学框架。亮点 阿尔茨海默病 （AD） 治疗的有意义益处的定义因疾病阶段和利益相关者的观点而异。可观察和有意义的结果必须考虑 AD 的临床生物学性质。具有统计学意义的效果或结果并不总是等同于临床意义。评估工具必须反映治疗后分期特异性的细微变化。真实世界的证据将支持对临床意义的共识、定义和解释。