An Additional Basic Science for Clinical Medicine: II. The Limitations of Randomized Trials

Although highly successful in investigating remedial therapy, randomized clinical trials have sometimes created rather than clarified controversy when the treatments were given for the complex problems involved in studying either the primary prevention of disease or the secondary prevention of adverse progression for an established disease. Another source of difficulty has been the inevitable conflicts created by two legitimate and justifiable but opposing policies regarding the fastidious or pragmatic goals of the trials. These problems limit the scope of clinical questions that can be answered successfully by randomized trials, but other limitations are produced by problems in logistics or ethics. Randomized trials are unfeasible for studying multiple therapeutic candidates, minor changes in therapy, "instabilities" due to rapid technologic improvements in available treatment, long-term adverse effects, studies of etiologic or other suspected "noxious" agents, and the diverse clinical roles of diagnostic technology. Consequently, despite the magnificent scientific achievements of randomized clinical trials, the foundation for a basic science of patient care will also require major attention to the events and observations that occur in the ordinary circumstances of clinical practice.