Can Underpowered Clinical Trials Be Justified?

As a physician-investigator, I have participated as an ad hoc reviewer for a number of years in the National Institutes of Health (NIH) Clinical Oncology Study Section, one of many chartered Initial Review Groups that reviews applications to fund cancer clinical trials and studies of biological materials derived from cooperative group clinical trials. This group is unique because of its charge and the members who comprise its body of reviewers. Every proposal is reviewed by at least three clinical investigators (usually physicians) with backgrounds in radiation oncology, medical or pediatric oncology, pathology, and a variety of other biomedical science disciplines. Additionally, a biostatician reviews each proposal to determine the validity of the method of design and of the data analysis plan. Even when a study is sufficiently important to conduct and its hypothesis is sound, one might expect that a review committee would disapprove a study that is poorly designed and that will not produce statistically significant results. All too often, however, protocols that are creative and important but flawed methodologically receive a positive review for a variety of reasons: the study is a great idea, it's a truly innovative approach, or the disease under study is terrible and without any effective treatment, so anything in this area would help. Yet is it ethical to conduct methodologically flawed clinical trials? More specifically, can we justify conducting studies with few participants, known as underpowered clinical trials, if these trials are unlikely to produce statistically significant results?