Meaningful benefit and minimal clinically important difference (MCID) in Alzheimer's disease: Open peer commentary

Approval of the anti-amyloid monoclonal antibodies has stimulated an important discussion of the value to be placed on the magnitude of slowing achieved by treatment compared to placebo.

The minimal clinically important difference (MCID) was reviewed in the context of other measures and analyses that provide perspective on the meaningfulness of treatment responses.

TheMCID is a clinician-anchored approach to making this determination. The MCID applies best to symptomatic therapies for which the drug-placebo difference remains constant. Disease-modifying therapies produce a progressive divergence of drug and placebo trajectories; early in the course the MCID would not be achieved, later the MCID will be achieved, and with continuing therapy the MCID will be exceeded. Clinicians are not the only stakeholders involved in determining the value proposition of slowing disease progression. Patient-reported outcomes and caregiver-related measures offer important complementary insights. Analytic approaches also widen the perspective on the observed drug-placebo differences. Risk ratios, numbers needed to treat versus number needed to harm, time-to-event analyses, and predictive benefits based on biomarkers all add depth to the discussion.

Multiple stakeholder perspectives are needed to determine the importance to be attributed to the therapeutic changes observed with monoclonal antibody therapies and other emerging treatments.