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ENCePP Guide on Methodological Standards in Pharmacoepidemiology


5.7. Systematic reviews and meta-analysis


Identification and integration of evidence derived from results from several studies with the same or similar research objective can extend our understanding of the research question. A systematic literature review aims to collect in a systematic and explicit manner all empirical evidence that fits pre-specified eligibility criteria to answer a specific research question and to critically appraise relevant results. A meta-analysis involves the use of statistical techniques to integrate and summarise the results of identified studies. The focus of this activity may be to learn from the diversity of designs, results and associated gaps in knowledge as well as to obtain overall risk estimates. An example of a systematic review and meta-analysis of results of individual studies with potentially different design is given in Variability in risk of gastrointestinal complications with individual NSAIDs: results of a collaborative meta-analysis (BMJ 1996;312(7046):1563-6), which compared the relative risks of serious gastrointestinal complications reported with individual NSAIDs by conducting a systematic review of twelve hospital and community based case-control and cohort studies, and found a relation between use of the drugs and admission to hospital for haemorrhage or perforation.


Systematic review and meta-analysis of observational studies and other epidemiological sources are becoming as common as those of randomised clinical trials (RCTs). Challenges in systematic reviews that assess treatment harms (Ann Intern Med 2005;142:1090-9) explains the different reasons why both are important in providing relevant information and knowledge for pharmacovigilance. However, the method of analysis differs when meta-analyses pool evidence from observational studies compared to RCTs.


A detailed guidance on the methodological conduct of systematic reviews and meta-analysis is reported in Annex 1 of this guide. This guidance includes links to other relevant resources.

It should be noted that meta-analysis, even of RCTs, shares characteristics with observational research as subjective criteria are often involved in the selection of studies to include. Careful planning in design of a meta-analysis and pre-specification of selection criteria, outcomes and analytical methods before review of any study results may thus contribute to the confidence placed in the results. A further useful reference is the CIOMS Working Group X Guideline on Evidence Synthesis and Meta-Analysis for Drug Safety (Geneva 2016).



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