As more drugs are being approved, is FDA getting less advice than in the past?
FDA maintains a vast network of outside advisors to provide input and counsel to the agency related to decisions on policy as well as product approvals. There are 31 advisory committees on matters ranging from food to medical devices to pediatric care. Within those focused on human drugs, there are 17 committees organized under therapeutic categories (Arthritis, Cardiovascular and Renal, Gastrointestinal, e.g.). Each committee is comprised of a number of experts, diverse for their expertise, geography and specialty – with some focused on statistics while others may be focused on areas of concentration within the category, such as the treatment of pediatric patients. There is an industry representative (non-voting) and a patient representative as well. Their terms are staggered – like the Senate – so that each year, some rotate off while others come on. FDA does not tap an advisory committee for every single approval or policy decision, but likely does when there are questions where they feel outside input is important.
Recently advisory committees (AdComms) have been in the news quite a bit due primarily to the controversy surrounding FDA’s decision to go against the advice of the Peripheral and Central Nervous System Drugs Advisory Committee in approving a treatment for Alzheimer’s where the committee vote was overwhelmingly against recommending approval. FDA does, from time to time, act contrary to a recommendation from an advisory committee – by my count a little over 10 percent of the time. This one, however, struck a nerve and after the decision, some members resigned from their role on the Advisory Committee.
And so we look at two things – how often is FDA consulting advisory committees and how many vacancies are there?
First, while the numbers are low enough that trends are not easy to discern, it does appear that FDA is consulting with advisory committees less and is doing so while more novel drugs are being approved. Below is a chart that looks at 3 numbers – the number of AdComms; the number of new molecular entities approved each year, and the number of drugs that had breakthrough therapy designation. Breakthrough Therapy is a pathway designed to expedite the consideration of a new drug for a serious condition where the drug may bring significant change to the treatment landscape. When Breakthrough Therapy (BT) designation is granted, then the drug gets Fast Track status and receives more intensive guidance – which can begin as early as Phase I clinical trials. The reason they are included here is that they could be a factor in the need for fewer advisory committee meetings – if these candidate compounds are demonstrating promise that gets them more intensive oversight it may negate the need for outside counsel. That said, BT would be a lagging indicator since it can be granted so early in the development process.
The blue represents the number of AdComms, Orange the number of new molecular entities and the gray the number of BT designations (Note that 2021 figures are through June 30):
What we can see here is that there is a significant body growing of BT designated compounds and a growing number, generally speaking, of new molecular entities being approved. At the same time, looking to 2018 when there were 29 meetings to consider new drugs, the number appears to be falling each year, with only 6 that occurred during the first half of 2021. Fewer meetings – more approvals.
If they did want to hold more, are they ready? That gets us to the issue of vacancies. Years ago, there would often be significant numbers of vacancies among the committees for considerable amounts of time. It is not an easy proposition to find willing and qualified participants who are not conflicted and to vet them all. It may be an easier management task now that meetings are virtual, but still it is a big organizational effort. Compared to yesteryear, it seems that vacancies are running pretty low. Of the 17 committees, only 6 appear to have vacancies:
- Bone, Reproductive and Urologic Drugs Advisory Committee -1
- Gastrointestinal Drugs Advisory Committee – 6
- Medical Imaging Drugs Advisory Committee – 1
- Oncologic Drugs Advisory Committee – 2
- Peripheral and Central Nervous System Drugs Advisory Committee – 4
- Pharmaceutical Science and Clinical Pharmacology Advisory Committee – 4
The most active of these committees with vacancies this year has been the Oncologic Drugs Advisory Committee. Also the vacancies on the Peripheral and Central Nervous System Drugs Advisory Committee largely reflect the protest of the FDA approval decision in Alzheimer’s.
FDA has had its reputation tested not only by that decision but by the events of the past few years that called into question a possible politicization of the process and all of the misinformation around COVID-19 and vaccinations. One pathway to preserving reputation is with the support of outside experts and with the advisory committee system, FDA has a built in means to add outside voices and credibility to the agency’s actions. But for that, it needs to be utilized.