A case study of multiple-treatments meta-analysis demonstrates that covariates should be considered

J Clin Epidemiol. 2009 Aug;62(8):857-64. doi: 10.1016/j.jclinepi.2008.10.001. Epub 2009 Jan 20.


Objective: To illustrate the potential and challenges of the simultaneous analysis of a network of trials, using as a case study the investigation of the relative effectiveness of four topical fluoride treatments and two control interventions (placebo and no treatment) in preventing dental caries in children.

Study design and setting: We performed multiple-treatments meta-analysis within a Bayesian framework by synthesizing six Cochrane reviews. We explored the compatibility between direct and indirect evidence and adjusted the results using a meta-regression model to take into account differences in the year of randomization across studies.

Results: The validity of our conclusions for the superiority of fluoride toothpaste as indicated from the initial network analysis using Bayesian methods was challenged when we adjusted for possible confounders. The network was dominated by studies comparing placebo with toothpaste, which were older and had been carried out in populations with higher baseline risk than studies involving other fluoride modalities.

Conclusion: After adjusting for possible differences across studies, we did not find clear evidence that any topical fluoride modality is more effective than any other. Multiple-treatments meta-analysis methods allow for more detailed investigations than naïve methods in the analysis of indirect evidence on treatment effects.

MeSH terms

  • Administration, Topical
  • Cariostatic Agents / administration & dosage*
  • Confounding Factors, Epidemiologic
  • Dental Caries / prevention & control*
  • Evidence-Based Medicine / methods
  • Fluorides / administration & dosage*
  • Humans
  • Meta-Analysis as Topic*
  • Mouthwashes
  • Randomized Controlled Trials as Topic
  • Review Literature as Topic
  • Toothpastes
  • Treatment Outcome


  • Cariostatic Agents
  • Mouthwashes
  • Toothpastes
  • Fluorides