Appraising iniparib, the PARP inhibitor that never was—what must we learn?

Iniparib is not a bona fide inhibitor of poly(ADP-ribose) polymerase (PARP), so the clinical results in this context should not be extrapolated to other PARP inhibitors in developmentPreclinical data on iniparib did not sufficiently elucidate the mechanism of action of this agent before clinical trials were initiatedPhase I trials should provide proof of mechanism and, ideally, proof of concept, in expansion cohorts to test biological hypotheses; early clinical trials of iniparib lacked proof of mechanismSelection of a patient population, and implementation and validation of predictive biomarkers, are critical to optimize drug developmentRandomized phase II trials have a significant rate of false positivity, so promising results should be interpreted prudently until other confirmatory studies are reportedPreclinical and clinical studies with negative results and efforts evaluating reproducibility of previously published data should be publically available to minimize the risk of publication bias