Lessons learned from recent cardiovascular clinical trials: Part II.

This is the first installment in a 4-part series of articles about our experiences with cardiovascular clinical research during the past 2 decades. From our vantage points as statistical and clinical researchers, we derive a series of lessons from recent clinical trials and incorporate them into principles designed to guide the practicing clinician who cares for patients with heart diseases. We are entering an era in which the imperative to understand the rational basis for diagnostic and therapeutic options has become a major force in medical care. Medical products (drugs, devices, and biologics) are proliferating simultaneously with a substantial restructuring of the delivery of health care, with a focus on evidence to support medical interventions. As the texture of evidence to support clinical practice becomes clearer, the imperative to investigate the effectiveness of behavioral interventions becomes more important. When coupled with concern about the rising cost of medical care, this proliferation of technological and behavioral intervention reinforces the view that we cannot afford to offer all possible diagnostic and therapeutic options to all patients. Recent publicity about therapies that were in widespread use and were later found to be detrimental1–3⇓⇓ has fueled this concern to extend well beyond the cost implications. The advent of genomics, proteomics, combinatorial chemistry, and advanced biomedical engineering will increase the importance of developing rational evidence about therapeutic risks and benefits. This effort to develop a rational basis for diagnostic and therapeutic decisions on the basis of quantitative assessments is a major component of evidence-based medicine. The randomized clinical trial (RCT) has emerged as the principal research tool for developing evidence to inform and influence clinical practice, particularly in the cardiovascular field. The practice of clinical trials is built on an understanding of the biology of disease, the structure of medical care delivery, …