A note on breast cancer trials with pCR-based accelerated approval.

Accelerated approval by the Food and Drug Administration (FDA), under the agency's Fast Track review designation, allows early approval of drugs to treat serious diseases and fill an unmet medical need based on a surrogate endpoint. In May 2012, FDA issued a draft Guidance for Industry on the accelerated approval of breast cancer drugs based on the surrogate endpoint "pathologic complete response" (pCR). The research reported in this article investigates potential issues in designing clinical studies for pCR-based accelerated approval. The correlation between pCR and long-term survival was investigated. Two sample comparisons based on a conditional survival model under different assumptions were performed and are discussed along with simulation results. The findings from this research may shed some light on the implementation of the FDA draft guidance.