In the middle of a busy clinic on a Monday morning, my assistant stopped me and said, “The FDA is on the line for you.” Over the next week, the Food and Drug Administration audited every patient I had enrolled in a clinical trial for a drug in regulatory review.
The auditors were impressive—professional, well-informed and meticulous, and they asked good questions. While auditing larger trial sites before final approval to verify the data within a new drug application is routine, the process can be anxiety-
Drug development in the United States is highly regulated. More than 90 percent of drugs that enter development fail.1 The mean cost for those that make it to FDA approval is a stunning $1.34 billion, although the rate of ultimate FDA approval has increased among drugs entering Phase III trials from less than 50 percent to 62 percent between 2010 and 2017.2
One place where the FDA recently received constructive criticism is the use of advisory committees.3 These are intended to be public forums that can offer insight to the FDA relating to decisions such as whether to approve a drug. They offer an opportunity for experts, patients, advocates and industry to offer views.
In 2010, more than half of new drug approvals had an associated advisory committee review. That dropped to 6 percent by 2021.3 We’re seeing this trend in retina as well. While pegaptanib, ranibizumab, aflibercept and ocriplasmin all received advisory committee reviews, more recent approvals, including brolucizumab, port-delivery system with ranibizumab and faricimab, did not.
There are many arguments on both sides, with some advocating for increased transparency regarding advisory committees,3 especially after the controversy surrounding aducanumab for Alzheimer’s disease.
Ultimately, all physicians play a critical role in this process. Brolucizumab is a perfect example. Intraocular inflammation and retinal vasculitis were only genuinely appreciated once the drug was commercialized.
I encourage you to engage in the regulatory process. It’s easy to submit any problem encountered with a product through an FDA Form 3500. And remember the American Society of Retina Specialists’ Research and Therapeutics (ReST) committee as well.
It’s a privilege to serve on multiple teams dedicated to developing better therapeutics for our patients. I’m glad we are Team Retina together. And remember to always pick up the phone when the FDA is on the line. RS
1. Hingorani AD, Kuan V, Finan C, et al. Improving the odds of drug development success through human genomics: Modelling study. Sci Rep 2019;9:18911.
2. Wouters OJ, McKee M, Luyten J. Estimated research and development investment needed to bring a new medicine to market, 2009-2018. JAMA. 2020;323:844–853.
3. Daval CJR, Kesselheim AS, Sarpatwari A. Improving the use of FDA advisory committees. N Engl J Med. 2022;387:675-677.