Meta-Analysis of Clinical Dose–Response in a Large Drug Development Portfolio

It described the data well, except for a single compound, which had nonmonotone dose–response. Compound-specific estimates and Bayesian hierarchical modeling showed that dose–response curves for most compounds can be approximated by E max models with “Hill” parameters close to 1.0. Summaries of the potency estimates show pharmacometric predictions of potency made before the first dose ranging study within a (1/10, 10) multiple of the final estimates for 90% of compounds.

The results of the meta-analysis, when combined with compound-specific information, provide an empirical basis for designing and analyzing new dose finding studies using parametric E max models and Bayesian estimation with empirically derived prior distributions.