Evaluating the Use of Nonrandomized Real-World Data Analyses for Regulatory Decision Making

Clin Pharmacol Ther. 2019 Apr;105(4):867-877. doi: 10.1002/cpt.1351. Epub 2019 Feb 25.


The analysis of longitudinal healthcare data outside of highly controlled parallel-group randomized trials, termed real-world evidence (RWE), has received increasing attention in the medical literature. In this paper, we discuss the potential role of RWE in drug regulation with a focus on the analysis of healthcare databases. We present several cases in which RWE is already used and cases in which RWE could potentially support regulatory decision making. We summarize key issues that investigators and regulators should consider when designing or evaluating such studies, and we propose a structured process for implementing analyses that facilitates regulatory review. We evaluate the empirical evidence base supporting the validity, transparency, and reproducibility of RWE from analysis of healthcare databases and discuss the work that still needs to be done to ensure that such analyses can provide decision-ready evidence on the effectiveness and safety of treatments.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Data Analysis
  • Databases, Factual / legislation & jurisprudence*
  • Decision Making
  • Delivery of Health Care / legislation & jurisprudence*
  • Evidence-Based Medicine / legislation & jurisprudence
  • Humans
  • Reproducibility of Results