Estimated effects of amyloid reduction on cognitive change: A Bayesian update across a range of priors

Abstract

AbstractINTRODUCTIONThe results of the CLARITY‐AD, GRADUATE I and II, and TRAILBLAZER‐ALZ 2 trials have rekindled discussion on the impact of amyloid‐targeting drugs. We use a Bayesian approach to quantify how rational observers would have updated their prior beliefs based on new trial results.METHODSWe used publicly available data from the CLARITY‐AD, GRADUATE I and II, and TRAILBLAZER‐ALZ 2 trials to estimate the effect of reducing amyloid on the clinical dementia rating scale, sum of boxes (CDR‐SB) score. A range of prior positions were then updated according to Bayes’ theorem using these estimates.RESULTSAfter updating with new trial data, a wide range of starting positions resulted in credible intervals that did not include no effect of amyloid reduction on CDR‐SB score.DISCUSSIONFor a range of starting beliefs and assuming the veracity of the underlying data, rational observers would conclude there is a small benefit of amyloid reductions on cognition. This benefit must be weighed against opportunity cost and side‐effect risk.Highlights The results of recent trials of amyloid‐targeting drugs have rekindled discussion on the impact of amyloid reductions achieved with amyloid‐targeting drugs on cognition. Prior to the announcement of trial results, beliefs about the effects of altering amyloid levels varied. For a range of starting beliefs, one would conclude there is a small benefit of amyloid reductions due to amyloid‐targeting drugs on cognition. The perceived value of individual drugs must balance the magnitude of this benefit against opportunity cost and risk of side effects.