title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Medicine, University of Alberta, 1702 College Plaza, 8215 - 112 Street NW, Edmonton, AB, Canada, T6G 2C8.
authors.forename: Salima
authors.initials: S
authors.lastname: Punja
authors.affiliation: Department of Biostatistics and Center for Evidence Based Medicine, Brown University School of Public Health, 121 South Main St., Box G-S121-8, Providence, Rhode Island 02912, USA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Schmid
authors.affiliation: Department of Pediatrics, University of Alberta, 11405-87 Avenue NW, Edmonton, Alberta, Canada, T6G 1C9.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hartling
authors.affiliation: Alberta Health Services, 9942 108 Street NW, Unit 642, Edmonton, Alberta, Canada, T5K 2J5.
authors.forename: Liana
authors.initials: L
authors.lastname: Urichuk
authors.affiliation: University of Queensland, Building 71/918 RBWH Herston, Brisbane, Queensland, Australia, 4029.
authors.forename: Catherine Jane
authors.initials: CJ
authors.lastname: Nikles
authors.affiliation: Complementary and Alternative Research and Education Program (CARE), Department of Pediatrics, University of Alberta, 1702 College Plaza, 8215 - 112 Street NW, Edmonton, AB, Canada, T6G 2C8. Electronic address: svohra@ualberta.ca.
authors.forename: Sunita
authors.initials: S
authors.lastname: Vohra
mesh_terms: D000293:Adolescent; D000661:Amphetamine / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D035843:Biomedical Research / Q000592:standards*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008774:Methylphenidate / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D008774:Methylphenidate; D000661:Amphetamine
keywords: ADHD; Amphetamine; Meta-analysis; Methylphenidate; N-of-1; Systematic review