N-of-1 Randomized Trials

Single-subject trials have a rich history in the behavioral sciences, but a much more limited history in clinical medicine. This chapter deals with a particular single-subject design, the N-of-1 randomized control trial (RCT). N-of-1 RCTs are single-patient multiple crossover studies of an intervention and usually one comparator. Typically, patients undergo pairs of treatment periods; random allocation determines the order of intervention and comparator arms within each pair and patients and clinicians are ideally blind to allocation. Patients and clinicians repeat pairs of treatment periods as necessary to achieve a convincing result. In the medical sciences, N-of-1 RCTs have seen limited use, in part due to lack of familiarity and feasibility concerns that arise in day-to-day clinical practice. Investigators may carry out a number of N-of-1 RCTs of the same intervention and comparator as part of a formal research study, aggregating across N-of-1 RCTs to develop population estimates. N-of-1 RCTs have demonstrated their utility in clarifying whether a clinical intervention is effective or not. Although N-of-1 trials have the potential for improving patient outcomes, the few small randomized trials comparing N-of-1 to conventional care have not demonstrated important benefits.