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



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.



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.



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.
Department of Pediatrics, University of Alberta, 1702 College Plaza, 8215-112 Street, Edmonton, Alberta T6G 2C8, Canada.
Salima
S
Punja
Guangxi University of Chinese Medicine, 179 Mingxiu E Road, Xixiangtang, Nanning, Guangxi, China.
Dongying
D
Xu
Department of Biostatistics and Center for Evidence Based Medicine, Brown University School of Public Health, 121 South Main Street, Box G-S121-8, Providence, RI 02912, USA.
Christopher H
CH
Schmid
Alberta Research Center for Health Evidence (ARCHE), Department of Pediatrics, University of Alberta, 4-496A Edmonton Clinic Health Academy, 11405-87 Avenue, Edmonton, Alberta T6G 1C9, Canada.
Lisa
L
Hartling
Information & Evaluation Services-Addiction and Mental Health, Alberta Health Services-Edmonton Zone, Rm 642, 9942-108 Street, Edmonton, Alberta T5K 2J5, Canada.
Liana
L
Urichuk
UQ Centre for Clinical Research, Faculty of Medicine and Biomedical Sciences, University of Queensland, Building 71/918, Royal Brisbane & Women's Hospital Campus, Herston, Queensland 4029, Australia.
Catherine Jane
CJ
Nikles
Complementary and Alternative Research and Education Program (CARE), Department of Pediatrics, University of Alberta, 1702 College Plaza, 8215-112 Street, Edmonton, Alberta T6G 2C8, Canada. Electronic address: svohra@gmx.ualberta.ca.
Sunita
S
Vohra
D000293:Adolescent; D000661:Amphetamine / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D016896:Treatment Outcome
D008774:Methylphenidate; D000661:Amphetamine
ADHD; Amphetamine; Meta-analysis; Methylphenidate; N-of-1; Systematic review