Diluting the signal: Class-level pooling and the ecological fallacy in meta-analyses of anti-amyloid monoclonal antibodies

Abstract

The recent Cochrane review of amyloid-β-targeting monoclonal antibodies concludes that future research on disease-modifying treatments for Alzheimer's disease should focus on alternative mechanisms. This conclusion rests on class-level pooling of nine pharmacologically heterogeneous agents, only three of which received FDA approval. This analytical decision commits an ecological fallacy at the drug level, diluting the signal of the agents that have modified clinical practice. This commentary situates the review within the broader literature, discusses the methodological origins of the error, and argues for stratified approaches that preserve clinical and regulatory relevance in syntheses of heterogeneous drug classes.