Note: This transcript has been created with a combination of machine ears and human eyes. There may be small differences between this document and the audio version, which is one of many reasons we encourage you to listen to the episode!
Dan Gorenstein: When it comes to the end of the pandemic, many have pinned their hopes on a vaccine.
President Donald Trump: We have a vaccine that’s coming, that’s ready.
Dr. Anthony Fauci: We will be able to make them available to the American public at the end of this calendar year.
DG: Just last week, the drugmaker Moderna announced it had enrolled the 30,000 people necessary to begin its Phase III trial.
While the process has moved at a record pace, making sure clinical trials include the people hardest hit by COVID-19 hasn’t been easy.
Today, why more diverse trials are important, even if they slow down the race for a COVID vaccine.
From the Annenberg Studio at the University of Pennsylvania, I’m Dan Gorenstein, and this is Tradeoffs.
Beau Garland: We’re working with all the big ones, with Pfizer, Sanofi. We’re working with Moderna, Sequirus, Novavax.
DG: That’s Beau Garland, and that list of big name pharma companies? Those are his clients.
He’s vice president of recruitment for Meridian Clinical Research, a company that signs people up for trials and then oversees the administration of the drug candidate.
BG: We take drugs or vaccines that the pharmaceutical companies develop and we need to test them for safety and efficacy. We give unbiased results back to the pharmaceutical companies who then in turn present it to the FDA.
DG: Meridian does this work from 23 different locations around the country, normally housed inside clinics.
Beau’s used to drug makers asking him to recruit hundreds, thousands of people fast.
But this year, after 20 years on the job, he’s been hit with a curveball.
BG: The FDA and the pharmaceutical companies to us have always promoted diversity in clinical trials and asked us to promote that. Now with the COVID vaccine studies, they are mandating it. They’re saying, “OK, you have to stop enrolling Caucasian people right now, we have plenty. Now we need to focus on African Americans or Hispanic or Asian” because they are really looking to get racial diversity that somewhat mimics the United States.
DG: To be clear, the FDA says it is not “mandating” diversity.
In a statement emailed to Tradeoffs the agency said:
SFX: “The FDA strongly encourages the enrollment of populations most affected by COVID-19, specifically racial and ethnic minorities.”
DG: Top federal health officials are well aware of the fact that Black, Latino, and Asian patients had much higher rates of hospitalization and death due to COVID-19 compared to whites.
Beau says, though, efforts to be more inclusive has meant taking longer to hit recruitment targets.
BG: Yes, if there were no restrictions on race, the 30,000 patients could be enrolled a lot quicker, for sure.
What’s hard, says Beau, is figuring out how to ramp up a more representative sample of people.
Before the pandemic, Beau used to send someone to do community outreach, to meet with big groups and pitch the idea of joining a clinical trial.
Pretty hard to find many large gatherings these days.
BG: Community outreach has come to a standstill.
DG: So now Beau says Meridian’s resorted to PSAs…
SFX: Spanish language PSA from patient
DG: email blasts, phone banks and more PSAs.
SFX: Hi everybody, this is Senator Tony Vargus. A couple of days ago I started a clinical trial in Omaha, Nebraska.
DG: Beau says the process has reminded him of a basic lesson he learned a long time ago.
BG: Our biggest success stories for racial diversity are in patients who are within the practice being able to talk to them and word of mouth, pass that on once I get any patients into clinical trials. And that grows like a weed. It has to be treating people well, educating them, and having them have a good experience, hopefully, and then go from there.
DG: Of course, the real question is what sort of leg work must companies do today so they are better positioned to bring in more diverse people for tomorrow’s trial.
DG: Dr. Jonathan Jackson is a “lapsed cognitive neuroscientist” — his words.
Over his career, he’s worked on the clinical side of research, specifically Alzheimer’s, but now, he focuses more on how clinical trials are run.
Jonathan Jackson: If you start to pull at this thread of why we don’t have diversity, you kind of rapidly come to the conclusion of clinical trials are just a damn mess.
DG: Jonathan heads the CARE Research Center, part of Massachusetts General Hospital.
The center’s mission is to create a culture of diversity and inclusion in clinical research.
He says the FDA has long taken a pro-diversity stance on paper.
Beginning in the 1990s the FDA and the National Institutes of Health began issuing guidance, sort of advice, promoting the importance of diversity and inclusion in clinical trials.
But the “guidance,” says Jonathan, is often lacking.
JJ: Every few years, we sort of wag a finger at them and say, “Do the best you can with with diversity.” But we don’t have that kind of guidance or enforcement or anything related to diversity and inclusion in clinical research. It’s just, “Do your best, sweetie.”
DG: The problem is, for some drugs, doing your best falls well short of ensuring safety for all patients.
Because of genetic differences and mutations, certain FDA-approved drugs work differently among different people.
For example, one drug used to treat epilepsy causes the skin of some people of Asian descent to blister and peel.
A nasty side-effect the FDA acknowledged in 2007 — 39 years after the drug’s approval.
This is not an anomaly.
Researchers reported that between 2008-2013, one-fifth of all newly approved drugs worked differently based on a patient’s race or ethnicity.
JJ: That was never part of anything that the drugmakers and their scientists understood or tested or tried to figure out. That’s something that we find out after a drug is on the market, after it’s being prescribed to people who look like me, and after we’re paying for it.
DG: In that same report, the authors wrote that clinical trials “need to adequately represent US minority populations” to be “safe and effective.”
So, where are we five years later?
JJ: Moderna just released their data on their Phase III COVID vaccine, and they were really, really happy that I think according to them, 4% were Asian, 10% were black or African American, 20% were Hispanic or Latinx, 63% were white. I think that is that is a great first approach. And honestly, Moderna is going to be held for the next several years for for setting a kind of a new standard for what diversity looks like in a clinical research study. But this is really minimum standard stuff.
DG: You’re saying that 10% of the people in the study were Black doesn’t necessarily answer all the questions that are needed from a scientific standpoint, from a safety stand, correct?
JJ: You need to have more than just different races in your research study. You need to understand where folks from each of these races come from. Do they come from rich neighborhoods or poor neighborhoods? Do they have great access to health care or terrible access to health care? All of these other factors have a huge effect on how somebody might react to getting COVID-19. And if you don’t highlight that information in addition to their race and ethnicity, then you might simply say these differences are because of someone’s race, when they might be because of some other driving factor.
DG: There’s good reason to think some people may be slow to line up for a vaccine when it’s available.
A Kaiser Family Foundation survey of Black Americans done this fall found just 49% would be willing to get a COVID-19 vaccine, even if scientists said it was safe, and it was free.
It may be too late to address some of the resistance that’s built up for these first COVID vaccines, but Jonathan suggests there are practical steps drugmakers could take for next generation treatments.
JJ: The first thing is to start early. As soon as you have a trial in mind, you need to start engaging with the communities that you want to see.
DG The second step — drugmakers and the companies like Meridian that manage trials can think more broadly about what inclusion and diversity mean.
JJ: Number one, diversity is about way more than just racial and ethnic minorities. And number two, we need to think about models of inclusion that have nothing to do with participating in trials. We need people on ethical review boards. We need people within these organizations and companies. We need people who are running the studies.
DG: Jonathan, how do clinical trials change if these additional people come on board?
JJ: When you have individuals who understand the local community, we understand the barriers that are in place to participate, and we even start to understand the barriers that drive something like vaccine hesitancy that we’ve seen with COVDI-19. Modeling as many sources of difference between the clinical trial and the real world is the best way that we can be better scientists and be very confident that what we’re seeing in the lab is what we’ll see in the real world.
DG: Jonathan hopes that the price drugmakers and companies like Meridian have paid in their quest to develop a COVID vaccine will make an impression.
The need for speed has been enormous, but without the ability to quickly recruit diverse patient panels, the whole process has moved slower.
That likely means the loss of people’s lives.
Jonathan says there are models for better ways to do this work. He points to the Alaskan Native tribes.
JJ: Those tribal communities have advanced a mode of community institutional review boards, as well as community data ownership, whereby they, the community members have a right of refusal when it comes to writing academic papers, and leveraging any information that was collected from their communities to advance scientific research. They have to be included. Sometimes they have to be compensated, but it can never happen without them. That is a radical new model of conducting clinical research.
DG: One small benefit to COVID upending health care is the pandemic’s ability to shine a light on long-ignored problems.
Jonathan says improving the representation of drug trials is an issue everybody wants fixed.
JJ: Everybody is full of good intentions. Everybody wants to do the right thing. It’s simply that we don’t value it as an intrinsic part of the scientific process. And until we do that with metrics, with enforcement, we are going to continue to struggle with this problem.
DG: I’m Dan Gorenstein, and this is Tradeoffs.