The conduct of randomized clinical trials (RCTs) is often a large-scale endeavor, with the potential to impact patients, clinicians, health care systems, and even the communities in which they are carried out. The effects of trials on participants may flow through the randomized study treatments or through other pathways, for example, by inducing changes to aspects of care separate from the randomized treatments. These effects may be beneficial (eg, participants may receive more careful evaluation, additional diagnostic studies, closer follow-up, or earlier detection of complications) or they may be harmful (eg, inconvenience or financial costs).