Cautionary tales in the interpretation of observational studies of effects of clinical interventions

Observational studies of the effectiveness of clinical interventions are proliferating as more 'real-world' clinical data (so called 'big data') are gathered from clinical registries, administrative datasets and electronic health records. While well-conducted randomised controlled trials (RCT) remain the scientific standard in assessing the efficacy of clinical interventions, well-designed observational studies may add to the evidence base of effectiveness in situations where RCT are of limited value or very difficult to perform. Rather than dismissing observational studies, we need to determine what circumstances may justify doing an observational study and when the study is sufficiently rigorous to be considered reasonably trustworthy. This article proposes criteria by which users of the literature might make such determinations.