Randomized control trials (RCTs) have been the established approach for measuring the measuring the safety and efficacy of drugs and biologic agents for >60 years and the tremendous advances in evidence-based care for disease owe a great deal to this method of treatment evaluation. RCTs are designed to minimize potentially confounding factors and sources of bias and confounding factors. While this is necessary for the establishment of causal relationships, it also limits our understanding of how effective a medication may be in actual clinical practice due to strict study inclusion criteria (e.g., exclusion of patients with comorbidities that may be common in patients with the disease being studied), restrictions in concomitant therapies, and potentially short durations of therapy. Real world evidence is collected in settings that more closely match how a medication will actually be used, such as pragmatic clinical trials, prospective observational studies, registries, case series, and retrospective clinical and healthcare claims studies. In real world studies, medications delivered are often based on physicians’ choices rather than a protocol, patient populations are much more heterogeneous than those in RCTs, and follow-up may extend for many years or even decades. Results from real world studies thus provide information about the effectiveness of a therapy over a long period under the wide range of conditions encountered in clinical practice. It is unlikely that real-world evidence will supplant the prospective RCT due to limitation in the ability to establish clear and unbiased relationships between medication exposures and outcomes. However, the combination of real world evidence and data from RCTs will permit us to paint a more complete picture of diseases, treatments, and their impacts on patients, and ultimately guide our way to delivery of better health care.
