The randomized controlled trial (RCT), the gold standard for evaluating the balance of risk and benefit in medical therapies, first emerged as a key clinical research tool in the mid-20th century thanks to visionary leadership of agencies such as the US National Institutes of Health (NIH), the UK Medical Research Council, and academic research institutions. Since then, clinical trials activity has shifted from the NIH and academia into the purviews of the medical products industry and regulatory authorities. Recent emphasis on evidence-based medicine, patient-centered outcomes research,1 and learning2 and accountable3 health care systems underscores the fact that most clinical trials fail to provide the evidence needed to inform medical decision making. However, the serious implications of this deficit are largely absent from public discourse, and a better balance between commercial interests and public health is critically needed.