title: Robustness assessments are needed to reduce bias in meta-analyses that include zero-event randomized trials.
abstract: OBJECTIVE
  Meta-analysis of randomized trials with binary data can use a variety of statistical methods. Zero-event trials may create analytic problems. We explored how different methods may impact inferences from meta-analyses containing zero-event trials.
  
  
  METHODS
  Five levels of statistical methods are identified for meta-analysis with zero-event trials, leading to numerous data analyses. We used the binary outcomes from our Cochrane review of randomized trials of laparoscopic vs. small-incision cholecystectomy for patients with symptomatic cholecystolithiasis to illustrate the influence of statistical method on inference.
  
  
  RESULTS
  In seven meta-analyses of seven outcomes from 15 trials, there were zero-event trials in 0 to 71.4% of the trials. We found inconsistency in significance in one of seven outcomes (14%; 95% confidence limit 0.4%-57.9%). There was also considerable variability in the confidence limits, the intervention-effect estimates, and heterogeneity for all outcomes.
  
  
  CONCLUSIONS
  The statistical method may influence the inference drawn from a meta-analysis that includes zero-event trials. Robustness assessments are needed to reduce bias in meta-analyses that include zero-event trials.
authors.affiliation: Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Denmark. erickeus@hotmail.com
authors.forename: F
authors.initials: F
authors.lastname: Keus
authors.forename: J
authors.initials: J
authors.lastname: Wetterslev
authors.forename: C
authors.initials: C
authors.lastname: Gluud
authors.forename: H G
authors.initials: HG
authors.lastname: Gooszen
authors.forename: C J H M
authors.initials: CJ
authors.lastname: van Laarhoven
mesh_terms: D015982:Bias; D003627:Data Interpretation, Statistical; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic