Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

Many postapproval drug trials are not directly comparable to previously published pivotal trials, particularly with respect to endpoint selection. Although treatment effects from pivotal trials supporting FDA approval of novel therapeutics based on non-continuous surrogate markers of disease are often larger than those observed among postapproval trials using surrogate markers as trial endpoints, there is no evidence of difference between pivotal and postapproval trials using continuous surrogate markers.