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Review
. 2020 Apr;107(4):843-852.
doi: 10.1002/cpt.1658. Epub 2019 Nov 14.

Examining the Use of Real-World Evidence in the Regulatory Process

Brett K Beaulieu-Jones  1 , Samuel G Finlayson  1 , William Yuan  1 , Russ B Altman  2 , Isaac S Kohane  1 , Vinay Prasad  3 , Kun-Hsing Yu  1
Affiliations
Review

Examining the Use of Real-World Evidence in the Regulatory Process

Brett K Beaulieu-Jones et al. Clin Pharmacol Ther. 2020 Apr.

Abstract

The 21st Century Cures Act passed by the United States Congress mandates the US Food and Drug Administration to develop guidance to evaluate the use of real-world evidence (RWE) to support the regulatory process. RWE has generated important medical discoveries, especially in areas where traditional clinical trials would be unethical or infeasible. However, RWE suffers from several issues that hinder its ability to provide proof of treatment efficacy at a level comparable to randomized controlled trials. In this review article, we summarized the advantages and limitations of RWE, identified the key opportunities for RWE, and pointed the way forward to maximize the potential of RWE for regulatory purposes.

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Conflict of interest statement

Therapy approval decisions are binary outcomes with the potential for profound impact on patients, employees, shareholders, and other stakeholders. Because of this, there represents an outsized incentive for a variety of parties to cheat the system, regardless of the study design. It was recently revealed that there was “data manipulation” in the data provided to the FDA during the approval process for Zolgensma.75, 76 In RWE, this poses a potentially bigger issue given the retrospective nature of data. The bar for exploitation is lower than prospective studies and exploitation becomes less black and white. It is not possible to ensure that trial organizers have not already analyzed the data to ensure that the control arm is penalized. This could be done through manipulation of the inclusion and exclusion criteria, the method of propensity matching between the trial subjects and the subjects derived from RWD or other intentional selections. For example, Sacks et al.50 found that historical control groups generally did significantly worse than RCT control groups across 50 reported clinical trials. The retrospective population selection task exhibits the opportunity for exploitation that is difficult to uncover, especially when considering potential financial implications. Although there is the opportunity for bad actors to cheat the system regardless of study type, RWE‐based studies can be performed by a smaller set of investigators where there are less exposure and transparency to the protocol.

All other authors declared no competing interests for this work.

References

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