A Short History of Bernard Fisher’s Contributions to Randomized Clinical Trials

Abstract

Dr. Bernard Fisher (1918-2019) was an early proponent of evidence-based medicine using the mechanism of prospective, multicenter, randomized clinical trials to test biological and clinical hypotheses. In this article, I trace how his early scientific work in striving to understand the nature of cancer metastasis through animal experiments led to a new, testable, clinical hypothesis: that surgery to remove only the tumor and a small amount of tissue around it was as effective as the more disfiguring operations that were then the standard treatment. Fisher’s work with the National Surgical Adjuvant Breast and Bowel Project (NSABP) using large, randomized clinical trials to demonstrate the veracity of this hypothesis led to a new paradigm in which the emphasis was placed on how systemic therapies used at an early stage of disease could effectively eradicate breast cancer for many patients. This new therapeutic approach led to the successful development of new treatments, many of which are widely used today. Ultimately, the new paradigm led to successfully preventing breast cancer in women who were at high risk for the disease but who had not yet been diagnosed with the disease. Throughout his entire career, Fisher championed the use of large prospective, randomized clinical trials despite criticism from many in the medical community who strongly criticized his use of randomization as a mechanism for testing clinical hypotheses. The approach he and the NSABP employed is still considered to be the highest standard of evidence in conducting clinical studies.