Meta-analysis of clinical dose response in a large drug development portfolio

It described the data well, except for a single compound, which had non-monotone 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 Emax models and Bayesian estimation with empirically-derived prior distributions.