Abstract
INTRODUCTION
The 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.
METHODS
We 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.
RESULTS
After 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.
DISCUSSION
For 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.
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This post is Copyright: Sarah F. Ackley,
Jingxuan Wang,
Ruijia Chen,
Melinda C. Power,
Isabel Elaine Allen,
M. Maria Glymour | February 22, 2024