Systematic review and meta-analysis of real-world evidence

This chapter introduces methodological principles for the systematic review and meta-analysis of real-world evidence (RWE) derived from non-randomized studies. It outlines key steps in identifying, extracting, and critically appraising such evidence, with emphasis on data quality, risk of bias, and comparability across study designs. Approaches for deciding whether and how to synthesize RWE—alone or in combination with randomized controlled trials (RCTs)—are discussed, including bias adjustment, hierarchical modeling, and cross-design synthesis. The concept of “evidence bars” is introduced to illustrate how the role of RWE varies across high-, medium-, and low-stakes decision contexts. A detailed case study on coronary in-stent restenosis demonstrates practical applications of these methods and highlights both opportunities and limitations of integrating RCTs and RWE. Finally, the chapter reviews perspectives from health technology assessment bodies, including frameworks from NICE and CADTH, underscoring the growing international momentum toward structured, transparent use of RWE in regulatory and reimbursement decisions.