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Methodological Overview: Meta-analyses of Adverse Effects Data from Case-Control Studies as Compared to Other Observational Studies

Date and Location




Sunday 22 September 2013 - 10:30 - 12:00


Presenting author and contact person

Presenting author

Su Golder

Contact person

Su Golder
Abstract text
Background: A diverse range of study designs are used in the evaluation of adverse effects in systematic reviews, including case-control studies. However, case-control studies do have potential biases that may lead to divergent findings compared to studies that use other methods. The extent of any discrepancy or heterogeneity between the pooled risk estimates from case-control studies and other study designs is a key concern for systematic reviewers. Objectives We aimed to ascertain whether the risk estimates from meta-analyses of case-control studies differ from that of other study designs. Methods: Searches were carried out in 10 databases in addition to reference checking, contacting experts, and handsearching key journals and conference proceedings. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from case-control studies could be directly compared with the pooled estimate for the same adverse effect arising from other types of observational studies. Results: We included 82 meta-analyses. Pooled estimates of harm from the different study designs had 95% confidence intervals that overlapped in 78/82 instances (95%). Of the 23 cases of discrepant findings (significant harm identified in meta-analysis of one type of study design, but not with the other study design), 16 (70%) stemmed from significantly elevated pooled estimates from case-control studies. There was associated evidence of funnel plot asymmetry consistent with higher risk estimates from case-control studies. On average, cohort or cross-sectional studies yielded pooled odds ratios 0.94 (95% CI 0.88-1.00) times lower than that from case-control studies, Conclusions: Empirical evidence from this overview indicates that meta-analysis of case-control studies tend to give slightly higher estimates of harm as compared to meta-analyses of other observational studies. However it is impossible to rule out potential confounding from differences in drug dose, duration and populations when comparing between study designs.