Delivering on Diversity: Clinical Trials and Healthcare Access

Clinical trials help people access tomorrow’s treatments today. In the age of precision medicine and tumor profiling, this statement is particularly true for oncology patients. According to a recent ProPublica article, even in Phase I trials, 20% of clinical trial participants now see a reduction in tumor size, compared with 5% of participants in the 1990s.

Unfortunately, even in clinical trials for new potential treatments for cancers that disproportionately impact African Americans, on average 4% of participants were black. This discrepancy between who is most impacted by a disease and who is participating in relevant clinical trials for new treatment options has real-world implications for disease management and treatment.

In this episode of our Delivering on Diversity series, we discuss the content of Caroline Chen and Riley Wong’s ProPublica article and delve into what the statistics mean for minority health. In the next episode, we will get into the solutions to this issue presented in the article and share a few ideas of our own.

Click on the image to listen now, or read below for a summary of the discussion.

(Music by Bensound)

Lindsey Wahlstrom-Edwards (LW): The article kicks off by saying that Multiple Myeloma disproportionately impacts African Americans, which is something that we all know to be true. There is a new drug on the market, Ninlaro, which is being heralded as a “savior” for patients. But only 13 of the clinical trial’s 722 participants were black.

There is an FDA scientist who wrote that “meaningful differences may exist” in how Multiple Myeloma affects black patients, what symptoms they experience, and how they respond to medications. So it’s pretty important that the clinical trial didn’t have a representative sample of African Americans.

But if you dig deeper into the article and you dig deeper into the issue [of diversity in medical research], it doesn’t just affect African Americans. In fact, it spans all minority groups in the United States. Part of this difference might come from the fact that income determines someone’s likelihood of participating in a clinical trial – it’s very much a middle-income practice – because if you look at issues like needing to take off of work, find child care, pay for travel expenses, etc, those are additional expenses that are harder to absorb if you don’t have some leeway in your budget. In addition, there are some really stringent inclusion criteria for clinical trials that might lead to less minority participation.

I’ve shared a ton of information. Let’s break it down. For me, Allison, the most telling statement in the article was the assertion that “not only do potentially ‘meaningful differences’ exist in how people of different races respond to treatments, but also folks who don’t partake in trials aren’t getting access to new potential treatments as soon as they are available.” What’s your take on that statement?

Allison Kalloo (AK): Clinical trials and access to health care are on opposite ends of a scientific continuum, but clinical trials and healthcare both depend entirely on science. Science demands evidence. And because minorities are healthcare consumers and are prescribed drugs like everybody else, and because drug approvals are based on the data gathered during clinical trials, when minorities are not adequately represented in these studies, not only does this science lack integrity, but minorities are relegated to accepting poor outcomes because nothing substantially new and different can come along to take its place.

How can I say that? Well, abundant peer-reviewed journal articles say so. Researchers have known for decades that many diseases affect minorities at higher rates than the rest of the population. There is consensus among researchers that minority underrepresentation in clinical trials contributes significantly to health disparities. There is just as much data linking inadequate access to healthcare with negative health outcomes. So the question has to be: “How can access for minority populations ever be described as adequate and equitable if the therapies on the market have historically not been proven safe and effective on minorities?”

LW: That’s a great point.

AK: The differences in our needs— in our metabolism of and response to drug compounds in some instances may prove to be negligible. Or they could prove to be significant. The point is we just don’t have enough information to know. We just don’t know what we don’t know. If we arbitrarily decide that “data is data” and it doesn’t matter what race study participants are, what we’re saying is that we are fine with an unscientific process and continuing not to know; that it’s okay to allow results from caucasian participants to be extrapolated onto non-white patients. So, by default, this is what’s happening.

Many researchers now acknowledge that this is inefficient and even irresponsible. But drug makers are systematically allowed to put products on the market without such evidence. Someone famously once said: “It makes no sense to develop new treatments for populations of patients who may be fundamentally different from those who will be using them.” True that. I say it’s also a lot like wearing someone else’s shoes.

LW: Yes, the ProPublica article is also pretty clear. The analysis found that 24 of 31 cancer drugs approved since 2015 had fewer than 5% black participants. African Americans make-up 13.4% of the population. So that’s a really big difference. Not only do these “meaningful differences” exist, but also, tomorrow’s treatments are in clinical trials today, so if you’re not participating in clinical trials then you’re not getting access to new potential treatments as soon as they are available in the pipeline.

And that has a bigger impact today than it did even 20 years ago, where even now in a Phase I trial, 20% of patients see tumors shrink or disappear, versus 5% in the 1990s (Dr. Karen Kelly). And, finally, the biggest thing we need to talk about in this article is that of the 31 drugs tested, 18 of them - so more than half - were for cancers that afflicted African Americans at least as much as whites, if not more. But still, on average, only 4.1% of trial participants were black.

AK: Exactly. This article underscores how the scarcity of black and other minority patients in clinical trials leaves unanswered the vital question of whether the drugs being made, prescribed and sold work equally as well for minorities as they do for white people. And while it focuses on the implications for African Americans, as you pointed out, other minority subpopulations are also underrepresented in clinical trials.

And you also hit on something that we need to emphasize and that is what has become much more stark and disturbing: There is no requirement of industry that their studies reflect disease prevalence or population breakdown by race and ethnicity. And this is even though the National Institutes of Health instituted a mandate for inclusion, little more than 25 years ago, but it’s still not really enforced.

LW: Can you share a few examples of that?

AK: Sure. African Americans, for example, have the highest rates of prostate cancer in the U.S. and twice as many Black men are likely to die of the disease. However, in the seven major prostate studies conducted from 2009 to 2015, only 3% of those studies’ participants were Black.

Another example that is highlighted in the article is that African Americans experience higher rates of non-small cell lung cancer, the most common type of lung cancer. However, when two drugs were recently approved for it, the data were based on studies in which only 2% of their participants were Black.

Many, many more examples exist of these disparities. And recent numbers are easier to track because they’re now required to be published by the FDA in the Drug Trials Snapshot. That’s been in place since 2015 and is available online. In it, the FDA detail what they approved by brand name and compound name, when it was approved, and the drug sponsors. And I’ve found that if you dig a little more deeply, as the article’s authors also did, you will find as I did that the vast majority of the drugs approved by the FDA since 2015 for diseases across therapeutic areas such as heart failure, Hepatitis C, multiple myeloma, IBS, stroke, HIV, even mental health issues like depression, bipolar and schizophrenia, you will discover, as I did that these FDA approvals came through on diseases that commonly impact minorities. At one point, I calculated that less than 24% of the studies these approvals were based on had enough data from minority participants to even draw any conclusions.

LW: Oh. That is just unacceptable.

AK: I agree. The reality is that even when the best scientific minds classify *race itself* as a risk factor for disease, the proper measures are not being taken by all responsible for research to ensure that study representation is respectable and the results are scientifically relevant and useful.

Meanwhile, the FDA officially acknowledges that not only do individuals from underserved populations gain access to new therapies when they participate in clinical research, but this additional data helps researchers to identify variations in cancers, for example, and that minority inclusion would also contribute to researchers being able to develop targeted treatments that actually work on the people actually affected.

LW: And we hear that there are biological differences between races, despite race being a “social construct”, and these are probably due to things like environmental or genetic factors, right?

AK: That is right. Race is widely viewed as a social construct. And race has been a way for humans to point out our differences, some say artificially, and to classify differences that oftentimes really don’t go more than skin deep. Of course, it dovetails with racism in this country and around the world, this concept that some human beings are inherently different and superior.

We’ve fought and continue to fight for the premise that there are fundamentally no differences between us and we’re all created equal and should be treated as equal. This is a justifiable social construct that most intelligent, humane, and compassionate people subscribe to. And on a grand scale, perhaps, it is also scientifically sound. But it can be a slippery slope when it comes to health and disease, and even medical research.

Starting with having to acknowledge inequalities in the system of health and health care and the impact of what’s termed the social determinants of health on the macro level which is effectively how our health is impacted by how we live, the obstacles we face in our larger environment, and the way we are able to move about the planet. But we also have to acquiesce to a lack of sameness in biology and genes that scientists are exploring on the micro level. Our pharmacogenetics can be very different, likely triggered more by environment, both historically and the world we currently navigate.

LW: Okay. So, we’re going to get some feedback on this. Let’s delve into it a little bit more deeply so that we can clarify what we mean.

AK: Sure. Some studies have documented important differences in the way that chemical compounds are metabolized across races. When scientists have examined data from different racial subgroups side by side, what they have found, for instance, is that blood thinners work better or less well depending on your race. For instance, patients of Chinese descent have a gene variation that makes Plavix ineffective, while patients of African descent are warned about the risk of excessive if not fatal bleeding when they take Coumadin. At this point, both drugs have a Black Box warnings from the FDA.

The same concerns exist when treating asthma patients. As the authors of this article noted, Albuterol has been shown to work less well for Black and Puerto Rican children than it does for children of white and Mexican descent.

Expert scientists are, in fact, hardpressed to understand the science behind these differences, but they are consistent on one thing: the need for more data. And we can’t produce more of that – not in a controlled environment where safeguards are in place, anyway — without people participating in clinical trials.