Abstract
The meta-analytic-predictive (MAP) approach is a Bayesian meta-analytic method to synthesize and incorporate information from historical controls in the analysis of a new trial. Classically, only a single parameter, typically the intercept or rate, is assumed to vary across studies, which may not be realistic in more complex models. Analysis of covariance (ANCOVA) is often used to analyze trials with a pretest-posttest design, where both the intercept and the baseline effect (coefficient of the outcome at baseline) affect the estimated treatment effect. We extended the MAP approach to ANCOVA, to allow for variation in the intercept and the baseline effect across studies, and possibly also correlation between these parameters. The method was illustrated using data from the Alzheimer's Disease Cooperative Study (ADCS) and assessed with a simulation study. In the ADCS data, the proposed multivariate MAP approach yielded a prior effective sample size of 79 and 58 for the intercept and the baseline effect respectively and reduced the posterior standard deviation of the treatment effect by 12.6%. The result was robust to the choice of prior for the between-study variation. In the simulations, the proposed approach yielded power gains with a good control of the type I error rate. Ignoring the between-study correlation of the parameters or assuming no variation in the baseline effect generally led to less power gain. In conclusion, the MAP approach can be extended to a multivariate version for ANCOVA, which may improve the estimation of the treatment effect.