Systematic reviews and meta-analyses of non-randomised studies

Randomised controlled trials (RCTs) are considered as the gold standard for clinical research because unlike other study designs, they control for known, and importantly, unknown confounders by randomisation. Evaluation of interventions should hence be ideally done by RCTs. However, RCTs are not always possible or feasible for various reasons, including ethical concerns and the need for time, effort, and funding. Difficulty in the generalisation of the findings of RCTs is also an issue given their rigid design. Non-randomised studies (non-RCTs) provide an alternative to RCTs in such situations. These include cohort, case-control and cross-sectional studies. Non-RCTs have the advantage of providing data from the real-life situation rather than that from the rigid framework of RCTs. The limitations of non-RCTs include selection bias and lack of randomisation that allow confounders to influence the results. At best, non-RCTs can only generate hypotheses for testing in RCTs. This chapter covers the methodology for conducting, reporting and interpreting systematic reviews and meta-analysis of non-RCTs.