FDA unease about faster drug approvalBMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j1691 (Published 06 April 2017) Cite this as: BMJ 2017;357:j1691
- Peter Doshi, associate editor, The BMJ
Days before Donald Trump took office, the Food and Drug Administration quietly released a report1 that reads as both a forceful defense of large randomized trials and a plea to save such “phase III clinical trial” testing requirements—arguably the most distinctive feature of drug regulation over the past half century—from extinction.
For an agency that marks each drug approval decision with a celebratory press release but generally does not publicly announce even the name of applications it rejects—the report is a surprisingly thorough compilation of 22 specific case studies of drugs, vaccines, and medical devices. In each case, the product showed promising results in phase II studies but failed to shine in phase III trials—and ultimately was not approved for the intended indication (box 1, table 1⇓).
Box 1: Understanding phase I, II, and III trials12
To gain regulatory approval, most drugs and biological products must successfully complete a series of clinical trials broadly classified in three phases:
Phase I studies—First test of a product in humans, usually healthy volunteers. Trials are generally short and aim to gain a rudimentary understanding of how the product interacts with the body. Multiple doses of a product are tested to learn about acute toxicity, and the information is used to help design phase II studies
Phase 2 studies are generally larger and longer than phase I studies. Participants have the disease or condition the product aims to treat or prevent. Efficacy and adverse event data are collected to help develop hypotheses for testing and determine whether the balance of benefit to harm is sufficient to justify phase III studies. Phase II studies often measure only laboratory values or biomarkers and are generally too small to confirm …