President Trump marked his return to the White House Monday night with a video imploring Americans not to let COVID-19 dominate their lives because the United States has “the best medicines in the world, and it all happened very shortly, and they’re all getting approved.” Trump has praised unproven treatments like hydroxychloroquine and convalescent plasma throughout the pandemic. His doctors’ use of an experimental drug to fight his COVID-19 diagnosis may inspire yet another Trump fixation. Over the weekend, Trump received an experimental antibody cocktail, which has not been approved by the FDA. In order to take the drug, Trump needed to submit an Individual Patient Investigational New Drug application, commonly referred to as a “compassionate use” request, to Regeneron, the company developing the drug, which received $450 million in federal funding this summer to develop COVID-19 vaccines and treatments as part of Operation Warp Speed. (It should be noted that Trump owns stock in Regeneron and is acquainted with the company’s CEO, Dr. Leonard Schleifer.)
To sort through the medical and ethical implications of the president’s “compassionate use” request, Intelligencer spoke to Holly Fernandez Lynch, a bioethics and law professor at the Perelman School of Medicine’s Department of Medical Ethics and Health Policy at the University of Pennsylvania.
What is “compassionate use”?
I think it’s best to refer to it as “expanded access,” which is the regulatory term. The idea is that it’s “compassionate” because you’re taking people who don’t have other options and giving them an investigational treatment, so it’s kind of viewed as the Hail Mary pass. But I want to push back a little bit on that framing because it’s not necessarily compassionate to give somebody something if you have no idea whether it works or is safe. The better framing is “expanded access.”
There are a couple of different types of expanded access, but the key criteria is that you have to be a patient who has a serious or life-threatening disease or condition, and that you have exhausted the available treatment options. Meaning that you wouldn’t use expanded access for prophylaxis — for prevention.
Second, you have to not be eligible to participate in a clinical trial. That’s really important because clinical trials are how we actually determine whether products are safe and effective. We need to make sure that people are first considering trial participation, and only if they’re ineligible for a trial, or there’s no trial at the site where they’re being treated, or something else is getting in their way of enrolling, that’s when you can consider expansive access as a possibility.
I have been working on research ethics and preapproval access for a while now, and my parents and my friends had no idea what I was doing with my life. Now, all of a sudden, expanded access is a household phrase.
Given what we know about the president’s condition, do you see him as someone who should qualify for expanded access?
It’s hard to say because we don’t exactly know what his condition is, and I don’t know whether there were any trials that he could have participated in. There is a regulatory requirement to have considered relevant trials, relevant alternative ways to get access to the investigational product, and only if you’re not eligible to participate in one can you get expanded access.
A clinical trial is specifically designed as research — it’s not necessarily being done for the benefit of patients who are being enrolled in that trial, it’s being done for the production of generalizable knowledge to inform evidence based practice for future patients. Now, lots of times, there is the possibility of direct medical benefit for the people who are enrolled in the trial. But that’s an incidental benefit; it’s not why the trial is being run. For expanded access, it’s not being done for this kind of rigorous research purpose; it’s being done for the benefit of that individual patient.
This is the president of the United States. Shouldn’t he get this sort of individualized treatment?
I think that’s based on a false premise that we know that investigational products are better than other things that might be used for treatment. We don’t know that, and that’s the whole reason why research is a critical priority, especially in a pandemic. These arguments were made in the Ebola outbreaks. They get made when people are facing really desperate circumstances: “People are dying! Give them everything we could possibly give them!” That is a surefire way to have difficulty figuring out what works and what is safe. It perpetuates the uncertainty for longer.
It’s important to contextualize this with some of the treatments that the president touted earlier. Hydroxychloroquine was his pet drug that he was really excited about. When Trump was tweeting about hydroxychloroquine, everyone and their mother wanted it. Once trials were done, it turned out not to be effective and it had really critical safety considerations. And then the convalescent-plasma expanded-access protocol became gigantic. Tens of thousands of patients were getting convalescent plasma through expanded access, because there was lots of chatter from the president and the White House about how great that product must be.
In the absence of reliable information being provided from the White House, there’s been so much speculation about the president’s health based on drugs, based on videos and pictures, and based on the patchwork timeline that’s been put together. What can we responsibly infer from all of that information?
Honestly, I mean all you can really infer is that there’s just a really disconcerting lack of transparency over the health of the leader of our nation. The American public deserves to know what’s going on with a president who may become incapacitated. People are talking about some of the side effects of dexamethasone — mood swings and irrational behaviors. That’s something that’s important for the public to be made aware of.
In every conversation that I’ve had about this over the past couple of days, there have been so many ifs. The first thing that people were saying was maybe he doesn’t really have it, maybe he’s gonna come out on the other side and say, “Look! I beat this thing and it was never an issue!” Then people were speculating that he’s much worse off than is being led on. Forcing the American public to hypothesize about what’s going on raises all these other questions about what we are being kept in the dark about.
I saw you retweet something about HIV-positive patients being criminally prosecuted for less risky behavior than Trump attending a fundraiser while symptomatic. I’m wondering what is the spectrum that bioethicists use to quantify risk behavior?
I want to be really careful about that particular tweet because I don’t think that HIV-positive patients should ever be criminally prosecuted. I was just pointing out the disproportionality: Patients who have done much less have been criminally prosecuted. We have an entire White House behaving completely recklessly over the course of months. I am not at all suggesting that criminal prosecution would be appropriate in this circumstance, but there are certainly ethical obligations to take precautions, to make sure that you are not putting other people in harm’s way.
The best example of that is what we just saw with his motorcade and the Secret Service trotting Trump out so he could wave to his supporters. Why on Earth would you expect somebody to put their health on the line for such a trivial purpose? Trump is wearing, from what I could see in the pictures, a cloth mask. It’s not even the strongest PPE that he could have been wearing! It’s just a complete disregard for the safety and well-being of others. This idea that he’s the only person that matters. It’s extremely ethically problematic for the leader of our country to be so cavalier with the health and safety of others.
As a bioethicist, what has stood out the most over the past few days?
You know, it’s funny because it’s hard to separate my experience as a bioethicist from my experience as an American citizen watching what’s been going on here. As bioethicists, we’re now seeing things that we’ve been thinking about, writing about, and worrying about with regard to access to investigational products being played on a national stage for all to see. For example, the importance of clinical trials or the importance of not making the assumption that investigational products are going to be better. Now we’re having this nationally televised microcosm where the president is getting VIP treatment. He’s a VIP, obviously, but that does not mean that he should be getting all of these experimental products thrown at him.
This isn’t the first time expanded access has come up during the Trump administration. Back in 2018, he pushed hard for and signed into law a piece of legislation called Right to Try, which increased availability to investigational drugs. The argument around Right to Try was that expanded access, which has been around for decades, is failing patients. That patients are dying while they wait for products to go through the FDA process. And now we have an example where Trump is getting access to a drug through the expanded-access pathway that he claimed was not adequate. It’s incredibly ironic.
This political theater matters because it sets an example for COVID patients suffering around the country, and the world. Trump received a Regeneron product and is claiming to be doing better. He also got dexamethasone and remdesivir, so it’s not like you could tease apart what is possibly making him better if he is in fact getting better. But now you know you’ve got to imagine that COVID patients are going to be clamoring to get access to the Regeneron product. The legal standard for an emergency-use authorization is extremely low, so it would not surprise me at all if the next push here from Trump is to say, “Oh, we’ve got to get an emergency-use authorization for the Regeneron product.”
Because he feels indebted to Regeneron? Or because his logic will be, “It worked on me and therefore it is a panacea”?
The latter. I don’t think the president has ever felt indebted to anyone about anything. I think he gets really excited about certain products that people tell him are great, and now he’s going to have this personal experience with this product.
How will bioethicists 15 or 20 years from now look back on this time?
There’s just loads of public attention on the FDA and the world of research right now because of COVID, but other disease areas have been focused on these challenges for a long time. ALS is a really good example of this, where patients have been pushing for greater access to investigational products — and the FDA has said, sorry, we have to prioritize trials. And then along comes COVID and the FDA is willing to issue emergency-use authorizations. You have patients with other diseases saying, “What’s going on here? We wanted investigational products. How can Operation Warp Speed get this amazing progress through research in just a matter of months, where we’ve been dying for a much longer period of time? Why can’t we get warp speed for whatever our disease is?” That kind of COVID exceptionalism and the disparities that we’re seeing with regard to pandemic versus non-pandemic diseases is an area that’s going to keep ethicists busy for a while. But everything old is new again. A lot of these same debates came up in the context of the HIV outbreak in the ’80s, where there were allegations of the FDA not going fast enough. It’s unique to the extent that the entire American public is focused on these issues, but the underlying issues themselves are kind of perpetual research-ethics challenges.
This interview has been edited and condensed for clarity.