Coronavirus in Context: Including All of Us in Clinical Trials

[MUSIC PLAYING] You're watching Coronavirus in Context. I'm Dr. John Whyte, Chief Medical Officer at WebMD. You know, there's a lot of discussions around the COVID vaccine-- about are we enrolling enough minorities. Well, guess what? That's the question for every clinical trial, for every drug that we're thinking about. And joining me today to help provide some insights into how to get more minority populations enrolled in clinical trials is Dr. Ed Ramos. Dr. Ramos is the Director of the Digital Clinical Trials at Scripps Research institute. Dr. Ramos, thanks for joining.

Absolutely. It's a pleasure to be here. Appreciate the invite.

Let's start off with this big research project that you're part of called All of Us. Good name. What is that all about?

I mean, the name really sets the tone, because I think it is paradigm shifting for the National Institutes of Health in terms of the different research studies that they've supported in the past. And that is clearly identifying that there has been a challenge in the access that individuals have to research studies-- not only the information that comes out of that but the opportunity to participate. And so All of Us, as a moniker and as a descriptor of the study, is really meant to embrace this new opportunity to come up with new methods for truly broadening participation in research studies and having the information that is gleaned from these studies be available to all individuals across the country.

Now, how is All of Us doing in terms of getting minorities to participate in clinical trials? You know, I spent time at the FDA working on who participates in clinical trials. And the numbers are strikingly low. You know, even on the site, I can look and see-- and I just want to read this to our audience-- that African-Americans are more likely to suffer from respiratory ailments than Caucasian Americans. But only 1.9%, less than 2%, of all studies of respiratory disease include minority populations. And you and I both know this is not unique to respiratory conditions. You know, even in diabetes, it's typically less than 10%. And that's a high number. But it's the same for neurology, for cardiovascular. How do we change this?

Yeah, you know, unfortunately, that list is a long one in terms of examples. And they've been persistent over the decades regardless of amazing new breakthroughs that the NIH has supported in the past. And so I think there's a number of approaches that are symbolized and captured within the All of Us research program that helped break that barrier. So the first is truly rethinking our relationship with the participant. And it's potentially small things in terms of what we call our participants-- so moving away from considering them subjects, but really considering them as partners in this effort. Establishing more of a bidirectional pipeline for information, so ensuring that obviously the researchers are gleaning a tremendous amount from the data that they collect.

But then also what are novel ways that we can now provide that back to the participants so they have some transparency in terms of how their data are being used, but perhaps more importantly now insight into, wow, this is how I could potentially think about my own health and potentially changing my own health behaviors? And then ultimately it comes down to ensuring that we're getting boots on the ground for all the different types of communities and populations that are represented within the US and recognizing that, even when you sub-categorize things in terms of white versus Latino, as well as African-Americans-- myself, my father is Puerto Rican. My mom's Peruvian. So Latino to me culturally means two very different things. And just within that group alone, it's far from monolithic. So having this understanding of what the cultural differences are potentially within a given group is extremely important.

But Dr. Ramos, what do you say to people-- let's play devil's advocate. A lot of clinical trials never reach recruitment. They don't get done, and maybe they were important therapies. Other trials take much longer than one would have thought because of retention. If we start making it more difficult, what some people might argue, to enroll a representative sample of the community-- is that doing a disservice to some people, because we're delaying potentially lifesaving therapies that are and take longer to come? Is there really this variability of response based by sex, race, age, ethnicity? And I am playing devil's advocate.

No, no. I mean, it's important to always take a different lens and framing on things to understand. And so a couple of reactions-- one of them, I think there is just a social justice perspective to this, ensuring that there is access and inclusion to all those that want to participate and feel like they have some level of ownership in their own health information. And I think that that's at the top of the list. There's also, most certainly, a data-driven, technical answer to that question as well. And that is you can take diseases and disorders, for example, that we know have some level of a genetic underpinning, for example.

But we also know that there are environmental influencers that may affect whether or not there is an increased predisposition or susceptibility to a particular disease. And so when you start pulling in these disparate groups, you're able to layer this information-- so an understanding, OK, does geography really affect, is it the types of food that they're eating, is it their availability of green space to be able to exercise. And this layering of information can only be gleaned from being able to have this representative sample and have this diversity in data collection and lived experience.

We have study it. We have to know it. Yeah, so it's not just about equity.

You have to study it. Absolutely.

But it is potentially about variability, as we've seen in hypertension with African-Americans, as we've seen in women in terms of some of the aspects of novel oral anticoagulant. So you know. Lots of data to suggest that there could be differences. And if we don't look for them, we won't find them. Now, I have to say I was very interested in your title of Director of Digital Clinical Trials. And there's been some discussion that coronavirus is actually going to make clinical trials easier. And you talk about-- I want to make sure I read it right-- democratizing clinical trials and that digital health is one of the ways to do that. Can you explain that to our audience?

So for me, it's extremely exciting to be able to explore things like, what is the gold the in-clinic standard? And are there, in fact, potentially even off-the-shelf devices that we could potentially use to get the same types of data, recognizing that there are caveats potentially in the context of it? But sometimes the gold standard in-clinic measurement that you could potentially lose-- you could potentially gain this ability now for continuous measurement instead of this episodic measurement. And that in and of itself can now take a completely different picture of understanding these health measures for a given individual. The democratization--

Has COVID accelerated these?

Yeah, so absolutely. So to kind of bring that full circle, I think that this notion of COVID-19 most certainly initially shutting down a lot of the in-person operations for a lot of health systems-- this wasn't the reason why we started the Digital Trial Center. But it certainly supported our philosophy that this, in fact, can be done even within a COVID world, because we're able to leverage these technologies and our approach in a remote manner.

Now, people have been trying to improve representation of minorities in clinical trials, let's be honest, 20, 30 years. I have to give a lot of credit to women's advocacy groups, Phyllis Greenberger's Society for Women's Health Research and others, who have really promoted inclusion of women. And there's been some progress, but we haven't seen it across the board. What's your reaction when-- and you probably know this-- that although the vaccine manufacturers have said they want to make sure they enroll minorities, they've struggled with getting minorities?

And there's no requirement that they do. You and I both know. I don't think anyone's going to say a vaccine is not approved if they don't have a certain percentage of minorities. So how do we really change this? You know, people have been trying all along. Do you feel pretty confident that digital tools and digital technologies are finally going to let us make some progress?

I think the opportunity is there with the right approach. I mean, there are most certainly-- again, kind of taking your devil's advocate lens there, there are scenarios in which it could exacerbate certain health disparities, right, when we start talking about potential access to technology. But for me, it is a moral requirement to ensure that especially those that are underserved, underrepresented, across so many aspects of this country are front and center-- especially knowing the data that we've observed and seen in terms of the impact of COVID-19 on Latino communities, on African-Americans, and on a number of other populations that kind of fall under this underserved, underrepresented umbrella.

Will digital technologies facilitate an improvement in how we bring in those communities? Again, I think there is enormous opportunity for us to do that. And that means ensuring-- and it starts with the participant. It starts with-- you know, you can take all of the technology and digital aspects out of this. If you don't have a right approach in terms of how you communicate, how you tell the story of what it is you're attempting to do and what it means for that person-- if you can't get over that initial hump, then it's a pretty steep hill for you to haul in terms of being able to reach out to different populations. But I think part of that comes with shifting this paradigm and broadening participation.

You know, one population I want to make sure that we address, that always seems to be added on at the end-- and I don't want to be doing that here. So I want to make sure we address rural populations. And that's been an area where, you know, there are lots of challenges for engaging with different populations. And when we talk about digital tools and digital technologies, there are some challenges in terms of broadband internet. How do we address the issue of rural populations? So we're not necessarily talking about specific race, age, ethnicity, but we're talking about geography as you referenced.

Yeah, definitely. And to be clear, when I categorize in terms of underrepresented and underserved, it most certainly is not specific to race and ethnicity. And geography is a huge part of that. Also individuals in the socioeconomic status-- there's a whole new set of considerations for those populations. But specific to rural, you know, I always think about some of the early genetic genomic studies in which you have this amazing promise of I'm going to peer into your DNA, your blueprint. And I'm going to be able to espouse all of these things about you in terms of family-- you know, explanations of bad past family history, ancestry. And when you paint this beautiful picture and you end with "but that's only if you can come into our clinic," that's so deflating for so many different populations.

But for an approach and a paradigm shift that we look to employ in the Digital Trial Center, as well as All of Us research program, are simple things-- like, all right, well, how do we spin up a salivary kit in a simple mailing that's out to individuals anywhere in the country that at least has a US zip code and access to mail. The ability to literally just spit in a tube and send it back, and be part of that beautiful picture that was painted initially, is extremely gratifying. So I think it's those types of solutions that don't necessarily have to be high tech, but that you recognize that there are ways that we can still bring them into the fold for all of this cutting edge research and science that we're doing.

Well, it's high tech in the sense that before people could not simply-- you know, they'd have to have labs called and complication.

[INTERPOSING VOICES]

That's right.

Now we're spitting into tubes and getting our genome.

Absolutely, no. Great point. Yes.

What do clinical trials look like, Dr. Ramos, five years from now? Is it all done in the home? Is it all done through, you know, sensors and trackers and robotics? Take out your crystal ball and tell us how they're going to run.

Actually I think a lot of what you just said is, in fact, true. I think that digital health technologies-- and we've seen just amazing advances in off-the-shelf devices that allow for interrogation of a number of different data variables. I do want to convey that there are opportunities for us to launch studies that leverage all of these wonderful technologies, but that can still build a real relationship with the participant. And sometimes that's as simple as a phone call, as a Zoom call, as welcoming them into the study and guiding them through clinical trial efforts that require a lot. That's a lot of burden on their end in terms of wearing different devices and sensors and so on. And we're excited to employ those strategies as well and then think about how can we potentially digitize that as we look to grow the scope and grow the scale for different studies.

Well Dr. Ramos, I want to thank you for your advocacy for enrolling diverse patient populations, for your innovation in research in digital tools as how we do that. And we're going to check in with you and see how we're doing over the next couple of years and in terms of recruitment.

Please do. I'll look forward to it.

And I want to thank you for watching Coronavirus in Context.