Black Participants Are Sorely Absent from Medical Research
Black participants are under-represented in clinical research.
After years of suffering from mysterious symptoms, my mother Janice Thomas finally found a doctor who correctly diagnosed her with two autoimmune diseases, Lupus and Sjogren's. Both diseases are more prevalent in the black population than in other races and are often misdiagnosed.
The National Institutes of Health has found that minorities make up less than 10 percent of trial participants.
Like many chronic health conditions, a lack of understanding persists about their causes, individual manifestations, and best treatment strategies.
On the search for relief from chronic pain, my mother started researching options and decided to participate in clinical trials as a way to gain much-needed insights. In return, she received discounted medical testing and has played an active role in finding answers for all.
"When my doctor told me I could get financial or medical benefits from participating in clinical trials for the same test I was already doing, I figured it would be an easy way to get some answers at little to no cost," she says.
As a person of color, her presence in clinical studies is rare. The National Institutes of Health has found that minorities make up less than 10 percent of trial participants.
Without trial participation that is reflective of the general population, pharmaceutical companies and medical professionals are left guessing how various drugs work across racial lines. For example, albuterol, a widely used asthma treatment, was found to have decreased effectiveness for black American and Puerto Rican children. Many high mortality conditions, like cancer, also show different outcomes based on race.
Over the last decade, the pervasive lack of representation has left communities of color demanding higher levels of involvement in the research process. However, no consensus yet exists on how best to achieve this.
But experts suggest that before we can improve black participation in medical studies, key misconceptions must be addressed, such as the false assumption that such patients are unwilling to participate because they distrust scientists.
Jill A. Fisher, a professor in the Center for Bioethics at the University of North Carolina at Chapel Hill, learned in one study that mistrust wasn't the main barrier for black Americans. "There is a lot of evidence that researchers' recruitment of black Americans is generally poorly done, with many black patients simply not asked," Fisher says. "Moreover, the underrepresentation of black Americans is primarily true for efficacy trials - those testing whether an investigational drug might therapeutically benefit patients with specific illnesses."
Without increased minority participation, research will not accurately reflect the diversity of the general population.
Dr. Joyce Balls-Berry, a psychiatric epidemiologist and health educator, agrees that black Americans are often overlooked in the process. One study she conducted found that "enrollment of minorities in clinical trials meant using a variety of culturally appropriate strategies to engage participants," she explained.
To overcome this hurdle, The National Black Church Initiative (NBCI), a faith-based organization made up of 34,000 churches and over 15.7 million African Americans, last year urged the Food and Drug Administration to mandate diversity in all clinical trials before approving a drug or device. However, the FDA declined to implement the mandate, declaring that they don't have the authority to regulate diversity in clinical trials.
"African Americans have not been successfully incorporated into the advancement of medicine and research technologies as legitimate and natural born citizens of this country," admonishes NBCI's president Rev. Anthony Evans.
His words conjure a reminder of the medical system's insidious history for people of color. The most infamous incident is the Tuskegee syphilis scandal, in which white government doctors perpetrated harmful experiments on hundreds of unsuspecting black men for forty years, until the research was shut down in the early 1970s.
Today, in the second decade of twenty-first century, the pernicious narrative that blacks are outsiders in science and medicine must be challenged, says Dr. Danielle N. Lee, assistant professor of biological sciences at Southern Illinois University. And having majority white participants in clinical trials only furthers the notion that "whiteness" is the default.
According to Lee, black individuals often see themselves disconnected from scientific and medical processes. "One of the critiques with science and medical research is that communities of color, and black communities in particular, regard ourselves as outsiders of science," Lee says. "We are othered."
Without increased minority participation, research will not accurately reflect the diversity of the general population.
"We are all human, but we are different, and yes, even different populations of people require modified medical responses," she points out.
Another obstacle is that many trials have health requirements that exclude black Americans, like not wanting individuals who have high blood pressure or a history of stroke. Considering that this group faces health disparities at a higher rate than whites, this eliminates eligibility for millions of potential participants.
One way to increase the diversity in sample participation without an FDA mandate is to include more black Americans in both volunteer and clinical roles during the research process to increase accountability in treatment, education, and advocacy.
"When more of us participate in clinical trials, we help build out the basic data sets that account for health disparities from the start, not after the fact," Lee says. She also suggests that researchers involve black patient representatives throughout the clinical trial process, from the study design to the interpretation of results.
"This allows for the black community to give insight on how to increase trial enrollment and help reduce stigma," she explains.
Thankfully, partnerships are popping up like the one between The Howard University's Cancer Center and Driver, a platform that connects cancer patients to treatment and trials. These sorts of targeted and culturally tailored efforts allow black patients to receive assistance from well-respected organizations.
Some observers suggest that the federal government and pharmaceutical industries must step up to address the gap.
However, some experts say that the black community should not be held solely responsible for solving a problem it did not cause. Instead, some observers suggest that the federal government and pharmaceutical industries must step up to address the gap.
According to Balls-Berry, socioeconomic barriers like transportation, time off work, and childcare related to trial participation must be removed. "These are real-world issues and yet many times researchers have not included these things in their budgets."
When asked to comment, a spokesperson for BIO, the world's largest biotech trade association, emailed the following statement:
"BIO believes that that our members' products and services should address the needs of a diverse population, and enhancing participation in clinical trials by a diverse patient population is a priority for BIO and our member companies. By investing in patient education to improve awareness of clinical trial opportunities, we can reduce disparities in clinical research to better reflect the country's changing demographics."
For my mother, the patient suffering from autoimmune disease, the need for broad participation in medical research is clear. "Without clinical trials, we would have less diagnosis and solutions to diseases," she says. "I think it's an underutilized resource."
Catching colds may help protect kids from Covid
A new study shows that the immune system's response to colds can help prepare it to defend against COVID-19 - but only in the very young.
A common cold virus causes the immune system to produce T cells that also provide protection against SARS-CoV-2, according to new research. The study, published last month in PNAS, shows that this effect is most pronounced in young children. The finding may help explain why most young people who have been exposed to the cold-causing coronavirus have not developed serious cases of COVID-19.
One curiosity stood out in the early days of the COVID-19 pandemic – why were so few kids getting sick. Generally young children and the elderly are the most vulnerable to disease outbreaks, particularly viral infections, either because their immune systems are not fully developed or they are starting to fail.
But solid information on the new infection was so scarce that many public health officials acted on the precautionary principle, assumed a worst-case scenario, and applied the broadest, most restrictive policies to all people to try to contain the coronavirus SARS-CoV-2.
One early thought was that lockdowns worked and kids (ages 6 months to 17 years) simply were not being exposed to the virus. So it was a shock when data started to come in showing that well over half of them carried antibodies to the virus, indicating exposure without getting sick. That trend grew over time and the latest tracking data from the CDC shows that 96.3 percent of kids in the U.S. now carry those antibodies.
Antibodies are relatively quick and easy to measure, but some scientists are exploring whether the reactions of T cells could serve as a more useful measure of immune protection.
But that couldn't be the whole story because antibody protection fades, sometimes as early as a month after exposure and usually within a year. Additionally, SARS-CoV-2 has been spewing out waves of different variants that were more resistant to antibodies generated by their predecessors. The resistance was so significant that over time the FDA withdrew its emergency use authorization for a handful of monoclonal antibodies with earlier approval to treat the infection because they no longer worked.
Antibodies got most of the attention early on because they are part of the first line response of the immune system. Antibodies can bind to viruses and neutralize them, preventing infection. They are relatively quick and easy to measure and even manufacture, but as SARS-CoV-2 showed us, often viruses can quickly evolve to become more resistant to them. Some scientists are exploring whether the reactions of T cells could serve as a more useful measure of immune protection.
Kids, colds and T cells
T cells are part of the immune system that deals with cells once they have become infected. But working with T cells is much more difficult, takes longer, and is more expensive than working with antibodies. So studies often lags behind on this part of the immune system.
A group of researchers led by Annika Karlsson at the Karolinska Institute in Sweden focuses on T cells targeting virus-infected cells and, unsurprisingly, saw that they can play a role in SARS-CoV-2 infection. Other labs have shown that vaccination and natural exposure to the virus generates different patterns of T cell responses.
The Swedes also looked at another member of the coronavirus family, OC43, which circulates widely and is one of several causes of the common cold. The molecular structure of OC43 is similar to its more deadly cousin SARS-CoV-2. Sometimes a T cell response to one virus can produce a cross-reactive response to a similar protein structure in another virus, meaning that T cells will identify and respond to the two viruses in much the same way. Karlsson looked to see if T cells for OC43 from a wide age range of patients were cross-reactive to SARS-CoV-2.
And that is what they found, as reported in the PNAS study last month; there was cross-reactive activity, but it depended on a person’s age. A subset of a certain type of T cells, called mCD4+,, that recognized various protein parts of the cold-causing virus, OC43, expressed on the surface of an infected cell – also recognized those same protein parts from SARS-CoV-2. The T cell response was lower than that generated by natural exposure to SARS-CoV-2, but it was functional and thus could help limit the severity of COVID-19.
“One of the most politicized aspects of our pandemic response was not accepting that children are so much less at risk for severe disease with COVID-19,” because usually young children are among the most vulnerable to pathogens, says Monica Gandhi, professor of medicine at the University of California San Francisco.
“The cross-reactivity peaked at age six when more than half the people tested have a cross-reactive immune response,” says Karlsson, though their sample is too small to say if this finding applies more broadly across the population. The vast majority of children as young as two years had OC43-specific mCD4+ T cell responses. In adulthood, the functionality of both the OC43-specific and the cross-reactive T cells wane significantly, especially with advanced age.
“Considering that the mortality rate in children is the lowest from ages five to nine, and higher in younger children, our results imply that cross-reactive mCD4+ T cells may have a role in the control of SARS-CoV-2 infection in children,” the authors wrote in their paper.
“One of the most politicized aspects of our pandemic response was not accepting that children are so much less at risk for severe disease with COVID-19,” because usually young children are among the most vulnerable to pathogens, says Monica Gandhi, professor of medicine at the University of California San Francisco and author of the book, Endemic: A Post-Pandemic Playbook, to be released by the Mayo Clinic Press this summer. The immune response of kids to SARS-CoV-2 stood our expectations on their head. “We just haven't seen this before, so knowing the mechanism of protection is really important.”
Why the T cell immune response can fade with age is largely unknown. With some viruses such as measles, a single vaccination or infection generates life-long protection. But respiratory tract infections, like SARS-CoV-2, cause a localized infection - specific to certain organs - and that response tends to be shorter lived than systemic infections that affect the entire body. Karlsson suspects the elderly might be exposed to these localized types of viruses less often. Also, frequent continued exposure to a virus that results in reactivation of the memory T cell pool might eventually result in “a kind of immunosenescence or immune exhaustion that is associated with aging,” Karlsson says. https://leaps.org/scientists-just-started-testing-a-new-class-of-drugs-to-slow-and-even-reverse-aging/particle-3 This fading protection is why older people need to be repeatedly vaccinated against SARS-CoV-2.
Policy implications
Following the numbers on COVID-19 infections and severity over the last three years have shown us that healthy young people without risk factors are not likely to develop serious disease. This latest study points to a mechanism that helps explain why. But the inertia of existing policies remains. How should we adjust policy recommendations based on what we know today?
The World Health Organization (WHO) updated their COVID-19 vaccination guidance on March 28. It calls for a focus on vaccinating and boosting those at risk for developing serious disease. The guidance basically shrugged its shoulders when it came to healthy children and young adults receiving vaccinations and boosters against COVID-19. It said the priority should be to administer the “traditional essential vaccines for children,” such as those that protect against measles, rubella, and mumps.
“As an immunologist and a mother, I think that catching a cold or two when you are a kid and otherwise healthy is not that bad for you. Children have a much lower risk of becoming severely ill with SARS-CoV-2,” says Karlsson. She has followed public health guidance in Sweden, which means that her young children have not been vaccinated, but being older, she has received the vaccine and boosters. Gandhi and her children have been vaccinated, but they do not plan on additional boosters.
The WHO got it right in “concentrating on what matters,” which is getting traditional childhood immunizations back on track after their dramatic decline over the last three years, says Gandhi. Nor is there a need for masking in schools, according to a study from the Catalonia region of Spain. It found “no difference in masking and spread in schools,” particularly since tracking data indicate that nearly all young people have been exposed to SARS-CoV-2.
Both researchers lament that public discussion has overemphasized the quickly fading antibody part of the immune response to SARS-CoV-2 compared with the more durable T cell component. They say developing an efficient measure of T cell response for doctors to use in the clinic would help to monitor immunity in people at risk for severe cases of COVID-19 compared with the current method of toting up potential risk factors.
In this week's Friday Five: The eyes are the windows to the soul - and biological aging?
Plus, what bean genes mean for health and the planet, a breathing practice that could lower levels of tau proteins in the brain, AI beats humans at assessing heart health, and the benefits of "nature prescriptions"
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on new scientific theories and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the stories covered this week:
- The eyes are the windows to the soul - and biological aging?
- What bean genes mean for health and the planet
- This breathing practice could lower levels of tau proteins
- AI beats humans at assessing heart health
- Should you get a nature prescription?