Randomized trials in single subjects: the N of 1 study

Abstract

Large-scale randomized trials are not available for all disorders, and conventional "trials of therapy" are susceptible to bias. Randomized controlled trials (RCTs) in individual patients (N of 1 RCTs) may provide a solution. In an N of 1 RCT, a patient receives treatments in pairs (one period of the experimental therapy and one period of either an alternative treatment or placebo, in random order), both patient and clinician are kept blind to allocation, and treatment targets are monitored. This type of RCT is useful in chronic, stable conditions in which the proposed treatment has a short half-life. Treatment targets usually include quantitative measurement of symptoms tracked through patient diaries. Pairs of treatment periods are continued until effectiveness is proved or refuted. The N of 1 RCT is potentially of great use in psychopharmacology and in drug development. The practical approach presented here will allow clinicians to conduct their own N of 1 RCTs.