N-of-1 trials can be aggregated to generate group mean treatment effects: a systematic review and meta-analysis

Objectives: To evaluate how data from n-of-1 trials may be used in systematic reviews and meta-analyses by examining the effects of amphetamine and methylphenidate for attention-deficit hyperactivity disorder (ADHD).

Study design and setting: Electronic search of MEDLINE, EMBASE, and PsychINFO for English language articles published from 1950 to 2013. N-of-1 trials of pediatric participants with ADHD that assessed either amphetamine or methylphenidate vs. placebo were included. The primary outcome was improvement of core symptoms of ADHD, which was assessed by multiple rating scales. Studies with obtainable individual participant data were included in the meta-analysis. Weighted mean differences were computed using a random-effects model.

Results: Nine studies were included in the amphetamine-placebo comparison and 10 in the methylphenidate-placebo comparison. Meta-analyses were consistently in favor of amphetamine in 10 of 11 ADHD symptom domains and methylphenidate in 7 of 12 symptom domains. A high degree of heterogeneity across participant treatment response was observed.

Conclusions: Meta-analysis of n-of-1 trials suggests that amphetamine and methylphenidate are effective treatments for pediatric ADHD. Synthesizing n-of-1 trials enables assessment of individual responses to treatment as well as aggregate summaries across individuals and studies. It offers a promising general approach with applications across diverse treatments and disorders.