Abstract

Real-world evidence (RWE) holds enormous promise, with some of that promise beginning to be realized in the evaluation of harms. However, in order to accomplish major strides in harms assessment, and ultimately in the evaluation of effectiveness, many steps have to be taken. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and International Society for Pharmacoepidemiology (ISPE) papers [1,2] outline those steps needed to have observational studies, based on data routinely collected in practice, “more closely approximate” randomized controlled trials (RCTs) [[3]]. The goal is praiseworthy because of the aspiration to be able to draw “causal conclusions” in combination with experimental studies (randomized controlled trials, RCTs), considered the gold standard for use as a major source of evidence, where data is allocated by investigators. However, RCT data are also increasingly being seen as problematic not only because of the costs, the length of studies, and the exclusion of major segments of the population, but also because of the controversies surrounding RCT interpretation. All of these factors conspire to make RCTs (even pragmatic clinical trials, PCTs) not as valuable as once believed, and cannot be regarded as the only mode of providing data for medical decision making. Thus, there is a need to have observational studies based on real-world data to come up with findings that can lead to trustworthy clinical practice guidelines and decision aids.