MDMA's next step towards FDA approval: 5 Questions for FDA advisory committee member Suzanne Robotti

Robotti discusses the role of advisory committees in the FDA’s decisions.

On Tuesday, June 4, the U.S. Food and Drug Administration’s Psychopharmacologic Drugs Advisory Committee is holding a meeting to discuss Lykos Therapeutics’ new drug application for MDMA-assisted therapy as a treatment for PTSD. The FDA says they expect to make a decision about the drug by mid-August, which could mark a major turning point for the legal and medical status of psychedelics. But as the FDA comes closer to a decision, former trial participants, advocates, and academics have raised major concerns about the methodology and practices used in the clinical trials Lykos submitted to the FDA. Participants and former researchers have alleged that the researchers failed to report some adverse events, and the non-profit research organization Institute for Clinical and Economic Review concluded that there is insufficient evidence for the efficacy of MDMA-assisted therapy in treating PTSD. Many are looking to Tuesday’s advisory meeting to see what experts make of the existing evidence, and for clues on what the FDA might do next. 

To explain the role of advisory committees in the FDA’s decisions, The Microdose spoke with Suzanne Robotti, founder of the nonprofit health news site MedShadow and a member of the FDA’s Drug Safety And Risk Management (DSARM) Advisory Committee. Robotti’s first experience with adverse drug effects was in utero, when her mother took a drug called diethystilbestrol, which was prescribed to prevent miscarriages. The drug was later found to disrupt the development of fetuses’ reproductive organs, and Robotti learned as a teen that her prenatal exposure to the drug meant she was not able to have children. Robotti applied to join the FDA’s DSARM committee in 2017 and is now serving her second four-year term. 

Let’s go over the basics of these FDA advisory committees. How many are there, who is on them, and how often do they hold meetings? 

There are 26 different advisory committees, each focusing on different areas. How often each advisory committee holds meetings is wildly different every year. In fiscal year 2022, there were 39 advisory committees held, divided among all 26 committees, and in 2021, there were 36. There were even fewer in 2020, because of COVID, and in general, there are fewer meetings almost every year. My committee is kind of an oddball committee; we almost never meet on our own, but get added to a lot of meetings about drugs that are new enough that there is a significant risk of damage. I am actually very surprised and disappointed that we were not involved in this upcoming meeting on MDMA. 

Each committee generally has between 7 and 20 members. There are four member types: a patient representative who is affected by a specific disease or condition, which is the role I have; an industry representative who is supposed to give a wider industry point of view; a consumer representative who is active in community-based or consumer organizations; and the rest are scientists. Those are clinicians or academics who have expertise in a particular field, like anesthesiology or toxicology. The first two member types cannot vote.

What exactly are these committees voting on? 

About ten days before a committee meets, members receive the data they’re expected to review, and it also includes questions they’ll discuss and vote on. I’ve had 1500 pages sent to me before; you have very little time to go through a lot of data. (Reporter’s note: The FDA’s briefing and draft questions for the June 4 advisory committee meeting are available on the FDA’s site.)

Dr. Robert Califf, who runs the FDA, has spoken out publicly about his preference to stop the voting. While the vote is important, the most fascinating part of the meeting is when committee members explain why they voted the way they did.

What are the votes based on?

You’re supposed to be focused on the data presented, not external data that might be published elsewhere. There are three areas advisory committees are not allowed to consider. First, you’re not supposed to be considering whether anyone can afford the drug. You’re also not supposed to consider off-label prescribing risk, or what the risk is that doctors will use it without permission for indications the drug has not been tested for. And the last thing you’re not supposed to consider: is this better than the standard of care? The drug does not have to do better than the standard, but members often look for “noninferiority,” which means it’s not worse than existing treatment. 

What kind of (official and unofficial) effect do these votes have on FDA approval? 

The votes are non-binding, and the FDA has famously gone against the advice of the committee, for instance, in the recent case of an Alzheimer’s drug. [Reporter’s note: The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted against approving the Alzheimer’s drug Aduhelm in 2020, and when the FDA approved it in 2021, two committee members resigned. The drug was later discontinued by its manufacturer after the U.S. Medicare system severely restricted its use and coverage.] 

It often makes headlines if the FDA goes against the advisory committee’s votes; it’s pretty unusual. I would estimate that about 90 percent of the time, the FDA follows the advice of the committee. 

You mentioned earlier that you were surprised your committee wasn’t asked to attend the June 4 meeting on MDMA-assisted therapy. What might you want people to know about drug risks if you had the floor? 

The FDA requires that applicants submit two clinical trials. I don't think I've ever seen a clinical trial that had more than 1800 people in it; most have a few hundred people, and generally, they’re in the study for six months to a year. That is not many people and it means the best answers you can get out of these studies are: does the drug probably work, and does it likely not kill people? Even with rare drugs, once approved there are probably 5,000 to 10,000 Americans taking the drug. If the drug is being advertised on TV, millions of people could start taking it. Here’s a statistic: according to one study, 33% of drugs approved by the FDA between 2001 and 2010 were later found to have significant safety issues, where the drugs’ labels had to be modified with a “black box” warning, withdrawn from the market, or, at minimum, manufacturers had to send a letter out to all prescribers. It took an average of about 4.2 years to discover those issues. It's a frightening number: 33%! The FDA is approving drugs, and 33% of them could do significant damage. 

The advice I give to people is that for every medicine you ever take, no matter how much you trust your doctor, no matter how long it's been on the market, just keep a record that you took it. How many times have you taken it, and how much? That’s particularly important if it is a new drug, or if it's a drug that can affect your fetus. Make sure you get all the prescribing information, create a Google alert for it, lock up all your info in the drawer so you have it in case you need it later, and then go on with your life. You must make your own decisions and take your own risks, but you’ve got to protect yourself. The doctor's not going to call you up and say, “Oh, by the way, that drug I gave you increases your risk of cancer.” 

This interview has been edited and condensed for clarity and length.