title: Basic study design influences the results of orthodontic clinical investigations.
abstract: OBJECTIVE
  Meta-analysis is the gold standard for synthesizing evidence on the effectiveness of health care interventions. However, its validity is dependent on the quality of included studies. Here, we investigated whether basic study design (i.e., randomization and timing of data collection) in orthodontic research influences the results of clinical trials.
  
  
  METHODS
  This meta-epidemiologic study used unrestricted electronic and manual searching for meta-analyses in orthodontics. Differences in standardized mean differences (ΔSMD) between interventions and their 95% confidence intervals (CIs) were calculated according to study design through random-effects meta-regression. Effects were then pooled with random-effects meta-analyses.
  
  
  RESULTS
  No difference was found between randomized and nonrandomized trials (25 meta-analyses; ΔSMD = 0.07; 95% CI = -0.21, 0.34; P = 0.630). However, retrospective nonrandomized trials reported inflated treatment effects compared with prospective (40 meta-analyses; ΔSMD = -0.30; 95% CI = -0.53, -0.06; P = 0.018). No difference was found between randomized trials with adequate and those with unclear/inadequate generation (25 meta-analyses; ΔSMD = 0.01; 95% CI = -0.25, 0.26; P = 0.957). Finally, subgroup analyses indicated that the results of randomized and nonrandomized trials differed significantly according to scope of the trial (effectiveness or adverse effects; P = 0.005).
  
  
  CONCLUSIONS
  Caution is warranted when interpreting systematic reviews investigating clinical orthodontic interventions when nonrandomized and especially retrospective nonrandomized studies are included in the meta-analysis.
authors.affiliation: Department of Orthodontics, School of Dentistry, University of Bonn, Welschnonnenstr. 17, Bonn 53111, Germany; Department of Oral Technology, School of Dentistry, University of Bonn, Welschnonnenstr. 17, Bonn 53111, Germany; Clinical Research Unit 208, University of Bonn, Welschnonnenstr. 17, Bonn 53111, Germany. Electronic address: snpapage@gmail.com.
authors.forename: Spyridon N
authors.initials: SN
authors.lastname: Papageorgiou
authors.affiliation: Department of Orthodontics, King's College London Dental Institute, Floor 27, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Guilherme M
authors.initials: GM
authors.lastname: Xavier
authors.affiliation: Department of Orthodontics, King's College London Dental Institute, Floor 27, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Cobourne
mesh_terms: D015982:Bias; D003625:Data Collection; D018865:Dental Research; D006801:Humans; D009970:Orthodontics; D063868:Patient Outcome Assessment; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012189:Retrospective Studies
keywords: Meta-analysis; Orthodontics; Prospective clinical study; Randomized controlled trial; Retrospective clinical study; Systematic review