Using Real-World Data to Extrapolate Evidence From Randomized Controlled Trials

Clin Pharmacol Ther. 2019 May;105(5):1156-1163. doi: 10.1002/cpt.1210. Epub 2018 Sep 24.


Randomized controlled trials (RCTs) provide evidence for regulatory agencies, shape clinical practice, influence formulary decisions, and have important implications for patients. However, many patient groups that are major consumers of drugs are under-represented in randomized trials. We review three methods to extrapolate evidence from trial participants to different target populations following market approval and discuss how these could be implemented in practice to support regulatory and health technology assessment decisions. Although these methods are not a substitute for less restrictive pre-approval RCTs or rigorous observational studies when sufficient data are available in the post-approval setting, they can help to fill the evidence gap that exists in the early marketing period. Early evidence using real-world data and methods for extrapolating evidence should be reported with clear explanation of assumptions and limitations especially when used to support regulatory and health technology assessment decisions.

Publication types

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

MeSH terms

  • Drug Approval / methods*
  • Evidence-Based Practice / organization & administration
  • Humans
  • Patient Selection
  • Randomized Controlled Trials as Topic / methods*