title: No evidence for intervention-dependent influence of methodological features on treatment effect.
abstract: OBJECTIVE
  The goal of this systematic review was to evaluate if the influence of methodological features on treatment effect differs between types of intervention.
  
  
  METHODS
  MEDLINE, Embase, Web of Science, Cochrane methodology register, and reference lists were searched for meta-epidemiologic studies on the influence of methodological features on treatment effect. Studies analyzing influence of methodological features related to internal validity were included. We made a distinction among surgical, pharmaceutical, and therapeutical as separate types of intervention. Heterogeneity was calculated to identify differences among these types.
  
  
  RESULTS
  Fourteen meta-epidemiologic studies were found with 51 estimates of influence of methodological features on treatment effect. Heterogeneity was observed among the intervention types for randomization. Surgical intervention studies showed a larger treatment effect when randomized; this was in contrast to pharmaceutical studies that found the opposite. For allocation concealment and double blinding, the influence of methodological features on the treatment effect was comparable across different types of intervention. For the remaining methodological features, there were insufficient observations.
  
  
  CONCLUSIONS
  The influence of allocation concealment and double blinding on the treatment effect is consistent across studies of different interventional types. The influence of randomization although, may be different between surgical and nonsurgical studies.
authors.affiliation: Department of Neurosurgery, Leiden University Medical Centre (LUMC), PO Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: W.c.h.jacobs@lumc.nl.
authors.forename: Wilco C H
authors.initials: WC
authors.lastname: Jacobs
authors.forename: Moyo C
authors.initials: MC
authors.lastname: Kruyt
authors.forename: Wouter A
authors.initials: WA
authors.lastname: Moojen
authors.forename: Ab J
authors.initials: AJ
authors.lastname: Verbout
authors.forename: F Cumhur
authors.initials: FC
authors.lastname: Oner
mesh_terms: D015982:Bias; D002986:Clinical Trials as Topic / Q000379:methods*; D004311:Double-Blind Method; D006801:Humans; D011897:Random Allocation; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design; D016896:Treatment Outcome
keywords: Allocation concealment; Effect modifier; Epidemiologic; Randomization; Research design; Risk of bias