Sequential multiple assignment randomized trials (SMARTs) have been used to advance treatments for complex problems that lack clearly defined interventions.1,2 Unlike in traditional clinical trials in which participants are randomly assigned to only one intervention or one intervention strategy,3,4 in SMARTs participants are randomly assigned to an intervention at two or more stages of the trial. The adaptive reallocation strategy constructs a tailored or personalized strategy of interventions on the basis of the individuals' responses.5-8 An example of a SMART design is reported in this issue of NEJM Evidence.9.