Estimating treatment effects in clinical studies of Alzheimer's disease: What are estimands and why do we need them?

Description

Hendrix and colleagues explained estimands, definitions of the treatment effect a trial intends to measure, and why Alzheimer's disease studies need them, in a 2026 guidance article. Regulators now expect trial objectives to be translated into clinical questions using an international framework with five attributes. They are the treatment, the population, the outcome variable, how it is summarized, and how events after treatment starts, such as stopping the drug or dying, are handled.

Hendrix walks through estimands in trials of anti-amyloid antibodies, including lecanemab and donanemab, and uses the evoke studies of semaglutide in early Alzheimer's as examples. Alzheimer's trials are especially tangled because patients add other medications, discontinue treatment, or die during follow-up, and each choice changes what the result means. The authors argue that naming the estimand aligns design, analysis, and interpretation, and that readers cannot compare effect sizes across studies without knowing which estimand each used.

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Source: https://europepmc.org/article/MED/PMC13508584