Abstract
Background
Statistical adjustment is often considered to control confounding bias in observational studies, especially case-control studies. However, different adjustment strategies may affect the estimations of odds ratios (ORs), and in turn affect the results of their pooled analyses. Our study is aimed to investigate how to deal with the statistical adjustment in case-control studies to improve the validity of Meta-analyses.
Methods
We carried out a series of Monte Carlo simulation experiments based on predesigned scenarios, and assessed the accuracy of effect estimations from Meta-analyses of case-control studies by combining ORs calculated according to different adjustment strategies. The strategies included fully adjustment of all preset confounders guided by causal inference, insufficiently adjustment of less confounders, and improperly adjustment of covariates other than confounders.
Results
For all scenarios with different strength of causal relations, combining ORs adjusted for confounders as far as possible would get the most precise effect estimation, regardless of the sampling approaches of case-control studies and the scale of Meta-analysis. By contrast, combining ORs that were not sufficiently adjusted for confounders or improperly adjusted for mediators or colliders would easily introduce bias in causal interpretation, especially when the true effect of exposure on outcome was weak or none.
Conclusions
Statistical adjustment guided by causal inference are recommended for effect estimation. Therefore, when conducting Meta-analyses of case-control studies, the causal relationship formulated by exposure, outcome, and covariates should be firstly understood through a directed acyclic graph, and then reasonable original ORs could be extracted and combined by suitable methods.
Causal inference in case-control studies
