Randomized control trials (RCTs) are the gold standard for estimating the efficacy of a treatment. They allow us to investigate treatment effects in a controlled setting designed to ensure reproducibility of the results, quality of data, and minimization of selection bias. In contrast, comparative effectiveness from real-world data (RWD) is traditionally regarded as inferior evidence, primarily due to its lack of randomization and limited availability of information on potentially relevant prognostic factors. As such, real-world evidence (RWE) has been mostly used to corroborate RCT results and for post-marketing monitoring.
Recently, the growing body of data from the real world, which accompanied the digitalization of health, has drawn increasing attention to RWD and its potential, leading to questions on whether comparative effectiveness evidence from RWD could support regulatory and HTA decisions.