Clinical Pharmacology & Therapeutics
Volume 109, Issue 5 Pages: 1159-1362 May 2021
Review – Open Access
Randomized Controlled Trials Versus Real World Evidence: Neither Magic Nor Myth
Hans‐Georg Eichler, Francesco Pignatti, Brigitte Schwarzer‐Daum, Ana Hidalgo‐Simon, Irmgard Eichler
Peter Arlett. Anthony Humphreys, Spiros Vamvakas, Nikolai Brun, Guido Rasi
First Published:16 October 2020
Compared with drugs from the blockbuster era, recently authorized drugs and those expected in the future present a heterogenous mix of chemicals, biologicals, and cell and gene therapies, a sizable fraction being for rare diseases, and even individualized treatments or individualized combinations. The shift in the nature of products entails secular trends for the definitions of “drugs” and “target population” and for clinical use and evidence generation. We discuss that the lessons learned from evidence generation for 20th century medicines may have limited relevance for 21st century medicines. We explain why the future is not about randomized controlled trials (RCTs) vs. real‐world evidence (RWE) but RCTs and RWE—not just for the assessment of safety but also of effectiveness. Finally, we highlight that, in the era of precision medicine, we may not be able to reliably describe some small treatment effects—either by way of RCTs or RWE.