Sham procedure versus usual care as the control in clinical trials of devices: which is better?

Principles of clinical trial design dictate that the placebo control is the most rigorous comparator by which to assess the efficacy of an intervention. In the case of procedural treatments, however, exposure to an inactive (or sham) procedure may be associated with substantial discomfort or risk, a phenomenon not typically encountered with placebo controls employed to assess noninvasive (e.g., orally administered) treatments and one that can influence the decision-making process with regard to choice of control arms. In considering whether or not a sham control is either appropriate or feasible in clinical trials of devices or procedures, the investigator must consider optimal standards of research design and ethical conduct, carefully balancing the risk of the sham control with the benefit that might be obtained from careful evaluation of the procedure itself. This calculation can be challenging when considered in the larger therapeutic context, for while the risk borne by research subjects exposed to sham control may not be insignificant, the aggregate risk to control subjects in a clinical trial may be less that the aggregate risk borne by patients who receive an untested therapy that is ultimately shown not to be beneficial after rigorous assessment in a placebo-controlled trial. This review addresses issues pertaining to the use of sham controls in clinical trials of devices and procedures and provides examples from the literature which demonstrate the importance of and controversy surrounding sham controls.