Are too many Phase III cancer clinical trials set up to fail?

Dr. Shen continued: "Our study shows that reducing false positive errors by imposing more stringent statistical threshold in Phase III trials is not likely to be practically feasible. A better strategy is to rethink the process that leads to the decision of moving a new therapy to Phase III testing to begin with. More research is needed in this regard.""Our study highlights the need to more efficiently identify which new therapies merit Phase III testing," said lead researcher Changyu Shen, PhD, Associate Professor at Harvard Medical School at the time this study was conducted. "In order to sustain the rate of innovation in cancer therapeutics and ensure that our patients have access to effective yet affordable therapies, the clinical trial pipeline in oncology must be efficient and accurate. Our work shows that in the past ten years, this has not been the case."

Most of the trials in this novel study focused on lung, breast, gastrointestinal, and hematologic cancers; trials with fewer than 100 participants were excluded, meaning rare cancer types were less likely to be included. The Phase III trials were predominately two-arm studies of an interventional regimen compared with a control treatment.

"This paper shows that a lot of drugs with 'positive' Phase III trials may have a smaller ultimate benefit than was expected, and that changing the threshold for statistical significance is not a quick fix," said Elizabeth A. Handorf, PhD, Associate Research Professor, Fox Chase Cancer Center, who was not involved in this research. "I think it highlights the need for more efficient study designs, like adaptive trials, and clear definitions of what makes an effect clinically meaningful."