Real-world effectiveness of new medicines should be evaluated by appropriately designed clinical trials

Abstract 

Objectives

Health care providers, policy makers, and importantly patients themselves are increasingly interested in the outcomes of clinical trials yet often expect different questions to be addressed than those commonly asked in conventional phase 3 trials.

Study Design and Setting

Review of methodological articles.

Results

Conventional randomized controlled trials (RCTs) emphasize internal validity through standardization and control but by design reduce external validity, that is, generalizability of results and conclusions. Ongoing uncertainty about effectiveness or safety of medical interventions in the real world is the major driver for developing improved phase 3b and phase 4 study designs. Factors that should improve the relevance of these real-world trials (RWTs) include choice of endpoints; investigator specialty, appropriate patient selection criteria; emphasis on patient–physician interaction; admittance of relevant interventions in all study groups; and more flexible, simple, and possibly event-driven study visits and procedures, while maintaining randomization as a critical element to address confounders.

Conclusion

Although we do not believe that RWTs will supplant conventional RCTs, properly designed RWTs will enrich our understanding of the effectiveness of new health care interventions and better inform patients and health care providers alike.

Keywords: Comparative effectiveness, Comparative trials, Randomized clinical trials, Pragmatic trials, Real-world trials, Drug comparisons, Pharmacoeconomics, Health economics