The impact of trial baseline imbalances should be considered in systematic reviews: a methodological case study

J Clin Epidemiol. 2007 Dec;60(12):1229-33. doi: 10.1016/j.jclinepi.2007.03.014. Epub 2007 Aug 24.


Objectives: It is possible for baseline imbalances to occur between treatment groups for one or more variables in a randomized controlled trial, although the identification and detection of baseline imbalances remain controversial. If trials with baseline imbalances are combined in a meta-analysis, then this may result in misleading conclusions.

Study design and setting: The identification and consequences of baseline imbalances in meta-analyses are discussed. Metaregression using mean baseline scores as a covariate is proposed as a potential method for adjusting baseline imbalances within meta-analysis. We will use a recent systematic review looking at the effect of calcium supplements on weight as an illustrative case study.

Results: Meta-analysis conducted using the mean final values of the treatment groups as the outcome resulted in an apparent, statistically significant, treatment effect. However, using a meta-analysis of baseline values, this was shown to be due to the baseline imbalance between treatment groups, rather than as a result of any intervention received by the participants. Applying the method of metaregression demonstrated that there was in fact a smaller, statistically insignificant effect between treatment groups.

Conclusion: The meta-analyst should always consider the possibility of baseline imbalances and adjustments should be made wherever possible.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Bias*
  • Calcium / pharmacology
  • Dietary Supplements
  • Humans
  • Meta-Analysis as Topic*
  • Randomized Controlled Trials as Topic
  • Review Literature as Topic*
  • Treatment Outcome
  • Weight Loss / drug effects


  • Calcium