English, Rebecca, Lebovitz, Yeonwoo, Griffin, Robert. "4 Clinical Trials in Cardiovascular Disease." Transforming Clinical Research in the United States: Challenges and Opportunities: Workshop Summary. Washington, DC: The National Academies Press, 2010.
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Transforming Clinical Research in the United States: Challenges and Opportunities
attack), to sudden cardiac death. The condition depends on the degree to which the coronary artery has been obstructed and the health effects the obstruction has caused. A diagnosis of ACS is made by evaluating the results of an electrocardiogram (ECG) and the presence or absence of certain enzymes in the body.
Clinical research efforts in ACS provide a useful model for examining large, multicenter effectiveness trials in an acute, life-threatening disease. Robert Califf, Vice Chancellor for Clinical Research and Director of the Duke Translational Medicine Institute, reflected on the notable successes of the ACS field in translating basic science into early clinical trials, and then into definitive trials that evaluate outcomes related to key clinical questions. Once effective treatments have been identified and disseminated, the final step is measuring their uptake in hospitals and making the results publicly available, which improves adherence to the treatments. A 2004 study examining hospital compliance with quality guidelines (those of the American College of Cardiology/American Heart Association) and in-hospital mortality rates revealed that a 10 percent increase in guideline adherence corresponded to an 11 percent reduction in mortality rates (Peterson et al., 2004). Califf also cited papers based on data from a national registry of myocardial infarction showing that U.S. hospitals show close to 100 percent uptake of evidence-based therapies for ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (non-STEMI) at both hospital admission and discharge. The result has been an approximately 30 percent reduction in the risk of death if a patient presents at a hospital with chest pain. Califf stressed that, to establish evidence-based therapies that individuals and institutions can be held accountable for using, clinical trials should be focused on answering the critical questions in that disease area; conversely, trials that are poorly designed and seek to answer peripheral or irrelevant questions should be avoided.
Califf reflected on the evolution of clinical trials in ACS. Califf was part of a small group of people who formed the TAMI Group to address the area of STEMI trials. The group received a small amount of money ($100,000) from Genentech to conduct a randomized controlled trial (RCT) with 340 participants. The trial protocol, or study plan, included three cardiac catheterizations per subject, and the trial results were published in the New England Journal of Medicine. Califf highlighted this example of an early ACS trial because he believes the same trial could not be conducted today given the extremely high cost of conducting trials and the large number of patients now required for cardiovascular outcome trials.
The International Study of Infarct Survival (ISIS) group at Oxford had a similar early trial experience that Califf likewise claimed could not be replicated in today’s clinical trial environment. The minimum sample size