Abstract With the recent approval of disease‐modifying treatments for mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) by the United States Food and Drug Administration (FDA), Medicines and Healthcare products Regulatory Agency (MHRA), European Medicine Agency's Committee for Medicinal Products for Human Use (EMA/CHMP) entities, there is a growing sense of urgency and renewed efforts to reassess and understand what constitutes a clinically meaningful benefit in the context of new treatments for AD care, despite the discordance between regulatory entities in regulatory decision‐making. While the concept of minimal clinically important difference (MCID) was introduced many years ago, there remains an ongoing debate about how best to evaluate and define clinical benefit in the context of emerging and new therapies for dementia. In this perspective piece, we assess how MCID can be applied to common endpoints and identify areas where MCID application or generation could be useful to enable a better valuation of therapeutic innovation. We offer recommendations for greater consistency in measures used to define MCID, and encourage the prioritized use of patient‐reported measures in early AD to build fieldwide consensus for MCID estimation methods and application in AD. Highlights There is no gold standard or field‐wide consensus on what constitutes a clinically meaningful change in Alzheimer's disease (AD) progression trajectories. Anchor‐based minimal clinically important difference (MCID) may be used as a tool that can be leveraged for greater contextualization of the clinical relevance of a treatment effect. Patient‐reported outcomes (PROs) should be used to define MCID, particularly within mild cognitive impairment (MCI), prodrome/mild AD groups. Greater consistency is needed in the outcome measures used to detect cognitive and functional change to define MCID. This will enable MCID comparisons and support replications of MCID estimates across AD populations. Observational data can augment the clinical characterization and impact of treatment effect and help establish a “ground truth” MCID. MCID estimates for AD outcomes may be used in regulatory submissions to help contextualize the importance of a statistically significant treatment effect.
Hamilton et al. (Tue,) studied this question.