Building clinically relevant outcomes across the Alzheimer's disease spectrum

Abstract

Demonstrating that treatments are clinically meaningful across the Alzheimer's disease (AD) continuum is critical for meeting our goals of accelerating a cure by 2025. While this topic has been a focus of several Alzheimer's Association Research Roundtable (AARR) meetings, there remains no consensus as to what constitutes a “clinically meaningful outcome” in the eyes of patients, clinicians, care partners, policymakers, payers, and regulatory bodies. Furthermore, the field has not come to agreement as to what constitutes a clinically meaningful treatment effect at each stage of disease severity. The AARR meeting on November 19–20, 2019, reviewed current approaches to defining clinical meaningfulness from various perspectives including those of patients and care partners, clinicians, regulators, health economists, and public policymakers. Participants discussed approaches that may confer clinical relevance at each stage of the disease continuum and fostered discussion about what should guide us in the future.

Open peer review commentary on building clinically relevant outcomes across the Alzheimer's disease spectrum

“…The paper opens by setting the stage "Undoubtedly, all stakeholders agreed that a therapeutic response which produced a clear and sustainable benefit, while altering the disease trajectory, constitutes a clinically meaningful outcome." 1 As the authors note, though, we are far from such an indubitable consensus. Bridging the ideal then and the messy now necessitates some tough slogging.…”

“…Agreement is imaginable across such a diverse group, but only should something exist that we do not have now. The paper opens by setting the stage “Undoubtedly, all stakeholders agreed that a therapeutic response which produced a clear and sustainable benefit, while altering the disease trajectory, constitutes a clinically meaningful outcome.” 1 As the authors note, though, we are far from such an indubitable consensus.…”

“…(3) When is it achieved? Third, three perspectives: “the patient, care partner, and clinician,” “regulators,” and “payers and health economists.” 1 …”

“…These nine categories are each detailed. The authors underscore that “determining whether an AD intervention is clinically meaningful remains a challenge.” 1 Only in the conclusion, however, is a central challenge spelled out: “How cognitive and functional change should be measured is complicated by a syndrome that has considerable heterogeneity in pathologies, phenotype, and rates of progression.” 1 …”

“…Third, three perspectives: "the patient, care partner, and clinician," "regulators," and "payers and health economists." 1 These nine categories are each detailed. The authors underscore that "determining whether an AD intervention is clinically meaningful remains a challenge."…”