Use of double-blind placebo-controlled N-of-1 trials among stimulant-treated youths in The Netherlands: a descriptive study.

Objectives An N-of-1 trial is a double-blind placebo-controlled randomized trial to objectively and systematically evaluate the individual's response. This approach seems extraordinarily suitable for assessing the efficacy of stimulants in the treatment of attention deficit hyperactivity disorder (ADHD). The aim is to examine the use of N-of-1 trials among youths in the Netherlands, the protocols used, and the continuation of stimulant treatment thereafter. Methods Physicians requesting N-of-1 trials with stimulants were interviewed about their rationale and protocol. Prevalence and continuation were investigated by extracting N-of-1 trials among youths <20 years of age from a large pharmacy dispensing database for 2000-2004. Results The main purpose of N-of-1 trials mentioned by physicians was the assessing of individuals' response and dose-finding. Trial length, dosing schedule and efficacy assessment differed per physician. Trials consisted of a maximum of two treatment periods per dose. The annual percentage of youths starting stimulant treatment with an N-of-1 trial fluctuated between 0.6% (3/462) and 3.3% (10/301). No statistical significant difference could be detected between the continuation of stimulant treatment with or without an N-of-1 trial (p=0.71). Conclusions N-of-1 trials with stimulants are infrequently and not optimally used in the Netherlands. The results of N-of-1 protocols described by physicians are of questionable value, due to the small number of treatment periods per dose. More uniformity in the protocols would make it easier to encompass the N-of-1 methodology in physicians' daily practice