Bayes analysis supports null hypothesis of anti‐amyloid beta therapy in Alzheimer's disease

Numerous clinical trials of anti‐amyloid beta (Aβ) immunotherapy in Alzheimer's disease have been performed. None of these have provided convincing evidence for beneficial effects. Using traditional frequentist meta‐analysis, the conclusion is that there is absence of evidence for a therapeutic effect, with a point estimate effect size of 0.05 (95% confidence interval −0.00 to 0.10, P = .055). In addition, this non‐significant effect equates to 0.4 points per year on the cognitive subscale of the Alzheimer's Disease Assessment Scale. This is well below the minimally clinically important difference. Bayesian meta‐analysis of these trial data provides strong evidence of absence of a therapeutic effect, with a Bayes factor of 11.27 in favor of the null hypothesis, opposed to a Bayes factor of 0.09 in favor of a treatment effect. Bayesian analysis is particularly valuable in this context of repeatedly reported small, non‐significant effect sizes in individual trials. Mechanisms other than removal of Aβ from the brain may be probed to slow progression of Alzheimer's disease.