An Interview with Robert Califf.

Abstract

In the late 1970s, when Robert Califf was in medical school, the heart was still a kind of medical terra incognita. Most cardiologists believed that a class of untimely heartbeats, known as premature ventricular contractions (PVCs), could predict sudden cardiac death. During his third year at Duke University Medical School, Califf, and his colleagues, showed that impaired left ventricular function was the true culprit. A few years later, as new clot-busting agents were being developed, Califf, by then a Duke faculty member, and colleagues predicted that one of the drugs, tissue plasminogen activator (tPA), would be most effective when followed immediately by angioplasty. They ran a multicenter clinical trial—the first of a series collectively known as Thrombolysis and Angioplasty in Myocardial Infarction (TAMI)—which showed the opposite: waiting to do the artery-opening procedure led to better outcomes. Inspired by the power of clinical trials to topple even his own beliefs, Califf embarked, with colleagues, on an ambitious series of groundbreaking trials comparing tPA and another clot-buster, streptokinase. The study—known as the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO)—established the superiority of tPA and also Califf's reputation as one of the most creative clinical scientists of his generation. In 1995, he founded the Duke Clinical Research Institute, which has grown to become one of the world's largest academic research organizations, having enrolled more than 1.2 million participants in 65 countries and with over 1300 employees. Admired for his ability to bring people from academia and clinical medicine together with members of industry—a connection that caused some to object when he was later nominated by President Obama for the post of Commissioner of the Food and Drug Administration (FDA)—Califf is also one of the top 10 most cited medical authors. Until recently, he continued to see patients …