To meta-analyze or not to meta-analyze? A combined meta-analysis of N-of-1 trial data with RCT data on amphetamines and methylphenidate for pediatric ADHD.

OBJECTIVES To assess how the inclusion of N-of-1 trial data into randomized controlled trial (RCT) meta-analyses impacts the magnitude and precision of yielded treatment effects, using amphetamines and methylphenidate for pediatric attention deficit hyperactivity disorder as a model. STUDY DESIGN AND SETTING We combined the N-of-1 and RCT data generated from previously conducted systematic reviews using parent and teacher ratings of hyperactivity and/or impulsivity as the outcome. Data were combined using standardized mean differences assuming a random effects model. The amphetamine and methylphenidate evidence were synthesized separately. RESULTS We found that the inclusion of N-of-1 trial data in the meta-analysis impacted both magnitude and precision. The addition of the N-of-1 trial data narrowed the confidence intervals in three of the four comparisons as compared to the treatment effect yielded by RCT-only data. Furthermore, the addition of N-of-1 trials changed the overall treatment effects yielded by the RCT-only meta-analyses from statistically nonsignificant to statistically significant in one of the four outcomes. CONCLUSIONS If the overall goal of a meta-analysis is to synthesize all available evidence on a given topic, then N-of-1 trials should be included. This study shows it is possible to combine N-of-1 trial data with RCT data and the potential merits of this approach.