There may be results from more than one study with the same or similar research objective, and identification and integration of this evidence can extend our understanding of the issue. 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 is the meta-analysis of results of individual studies with potentially different design e.g. Variability in risk of gastrointestinal complications with individual NSAIDs: results of a collaborative meta-analysis (BMJ 1996;312:1563-6), 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.
A systematic literature review aims to collect all empirical evidence that fits pre-specified eligibility criteria to answer a specific research question. These reviews use systematic and explicit methods to identify and critically appraise relevant research, and to analyse the data included in the review. A meta-analysis involves the use of statistical techniques to integrate and summarize the results of identified studies.
Systematic review and meta-analysis of observational studies and other epidemiological sources are becoming as common as those of 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.
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 randomised controlled trials, shares characteristics with observational research: the studies are often produced according to an unplanned process and subjective processes are involved in 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 add appreciably to the confidence that is 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).
|10. Specific topics|
|Annex 1.||Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes|