2009 Ancel Keys Memorial Lecture—Drug Therapies for the Prevention of CVD Events: Trials and Errors
Drug therapies for risk factors such as high levels of blood pressure, lipids, and glucose represent, in Geoffrey Rose’s terms, a high-risk approach to a population-based problem. The purpose of these therapies is to prevent cardiovascular events, yet the US Food and Drug Administration generally approves new medications for these conditions on the basis of premarket studies that use surrogate end points. It is not feasible to address all questions about the efficacy and safety of drugs during the premarket phase, so postmarket evaluation is crucial. Historically, however, drug approval separates the period of intense evaluation from the period of intense marketing. Between 1980 and 2005, prescription drug expenditures increased from $12 to $200 billion. The expansion of the pharmaceutical industry in the second half of the twentieth century has provided a number of safe and effective medications for many conditions. The health of Americans has clearly benefited in quality and duration of survival. With several notable exceptions, however, the NIH has largely turned the evaluation of drug treatments over to industry, and the results of key NIH trials must often contend with industry marketing to influence practice. The duty to provide a return on investment to shareholders tends to create for industry an asymmetric interest in safety and efficacy. As a result, the design, conduct, and reporting of some industry-funded studies remain a public health problem. The current approach to the evaluation of the safety and efficacy of medications occasionally provides an unreliable patchwork of evidence about health outcomes and incomplete information about the risk–benefit profiles of new drug therapies. For medications that are well evaluated, single–risk-factor approaches to treatment decisions may limit their benefit to the population.