title: The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method.
abstract: BACKGROUND
  The DerSimonian and Laird approach (DL) is widely used for random effects meta-analysis, but this often results in inappropriate type I error rates. The method described by Hartung, Knapp, Sidik and Jonkman (HKSJ) is known to perform better when trials of similar size are combined. However evidence in realistic situations, where one trial might be much larger than the other trials, is lacking. We aimed to evaluate the relative performance of the DL and HKSJ methods when studies of different sizes are combined and to develop a simple method to convert DL results to HKSJ results.
  
  
  METHODS
  We evaluated the performance of the HKSJ versus DL approach in simulated meta-analyses of 2-20 trials with varying sample sizes and between-study heterogeneity, and allowing trials to have various sizes, e.g. 25% of the trials being 10-times larger than the smaller trials. We also compared the number of "positive" (statistically significant at p < 0.05) findings using empirical data of recent meta-analyses with > = 3 studies of interventions from the Cochrane Database of Systematic Reviews.
  
  
  RESULTS
  The simulations showed that the HKSJ method consistently resulted in more adequate error rates than the DL method. When the significance level was 5%, the HKSJ error rates at most doubled, whereas for DL they could be over 30%. DL, and, far less so, HKSJ had more inflated error rates when the combined studies had unequal sizes and between-study heterogeneity. The empirical data from 689 meta-analyses showed that 25.1% of the significant findings for the DL method were non-significant with the HKSJ method. DL results can be easily converted into HKSJ results.
  
  
  CONCLUSIONS
  Our simulations showed that the HKSJ method consistently results in more adequate error rates than the DL method, especially when the number of studies is small, and can easily be applied routinely in meta-analyses. Even with the HKSJ method, extra caution is needed when there are = <5 studies of very unequal sizes.
authors.affiliation: Department for Health Evidence (HEV), Radboud University Medical Center, Huispost 133, P,O, box 9101, Nijmegen, HB 6500, The Netherlands. Joanna.intHout@radboudumc.nl.
authors.forename: Joanna
authors.initials: J
authors.lastname: IntHout
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: George F
authors.initials: GF
authors.lastname: Borm
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data*; D003139:Common Cold / Q000188:drug therapy; D003627:Data Interpretation, Statistical; D006801:Humans; D016017:Odds Ratio; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000401:mortality; D016016:Proportional Hazards Models; D018401:Sample Size; D015032:Zinc / Q000627:therapeutic use
chemical_list: D015032:Zinc