Ethical issues in rheumatology clinical trials.

Clinical trials in rheumatology are necessarily associated with an array of ethical issues that vary according to the type of trial under consideration. Difficult questions arise related to the appropriateness of enrolling normal volunteers or patients with disease in early phase toxicity studies of new agents. Prevention studies raise important questions regarding the exposure of a population of patients to an intervention with known adverse effects, even though prevention is not ensured. Postmarketing studies, although critically important in determining the true and long-term effects of therapies in a real-world setting, are sometimes designed solely for marketing purposes that do not contribute to meeting such goals. Regardless of the type of trial, selecting the appropriate control arm, the outcome measure, and 'rescue' or withdrawal provisions requires attention to pragmatic as well as ethical concerns. In addition, randomization is only ethically appropriate when, in addition to other conditions, clinical equipoise pertains to the treatment arms. Additional formative research is needed to improve the design of clinical trials and the informed consent processes for them. Finally, training in clinical research methods, which encompasses research ethics, is needed for rheumatologist investigators to ensure that participants are protected and that the results obtained from studies will be sound and ultimately applicable to clinical care.