Emulations of oncology trials using real-world data: a systematic literature review

Abstract

By evaluating published emulations of oncology randomized control trial (RCT) studies in which both the active and comparator groups are sourced from real-world data (RWD) and target trial results are available for benchmarking, this systematic review aims to gain insight into factors related to emulation performance. Thirteen oncology emulation studies using various types of RWD were identified through an online database search of PubMed through 2022. Based on the ROBINS-I tool, most studies (n = 8) had a serious risk of overall bias driven by risk of bias from confounding. Approximately half of the studies (n = 6) fully proxied the RCT entry criteria. Of 11 RWD studies that provided sufficient detail to quantify emulation performance, the emulation hazard ratio (HR) estimate fell within the 95% confidence interval (CI) of the trial estimate in 9 of the studies. There were no clear trends between risk of bias or degree to which the entry criteria were proxied and emulation performance. Findings may have been influenced by publication bias and researcher degrees of freedom, as only one emulation study preregistered its protocol. Tools for comprehensively characterizing factors that affect emulation performance, including the real-world clinical context as it relates to the RCT research question, are needed to evaluate the feasibility of a RCT emulation. This article is part of a Special Collection on Pharmacoepidemiology.

Keywords: oncology; real-world data; real-world evidence; target trial emulation.