BACKGROUND: Systematic reviews of healthcare interventions most often focus on randomized controlled trials (RCTs). However, certain circumstances warrant consideration of observational evidence, and such studies are increasingly being included as evidence in systematic reviews.
METHODS: To illustrate the use of observational evidence, we present case examples of systematic reviews in which observational evidence was considered as well as case examples of individual observational studies, and how they demonstrate various strength of evidence domains in accordance with current Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) methods guidance.
RESULTS: In the presented examples, observational evidence is used when RCTs are infeasible or raise ethical concerns, lack generalizability, or provide insufficient data. Individual study case examples highlight how observational evidence may fulfill required strength of evidence domains, such as study limitations (reduced risk of selection, detection, performance, and attrition); directness; consistency; precision; and reporting bias (publication, selective outcome reporting, and selective analysis reporting), as well as additional domains of dose-response association, plausible confounding that would decrease the observed effect, and strength of association (magnitude of effect).
CONCLUSIONS: The cases highlighted in this paper demonstrate how observational studies may provide moderate to (rarely) high strength evidence in systematic reviews.