Virtual Clinical Trials Are Letting More People of Color Participate in Research
Herman Taylor, director of the cardiovascular research institute at Morehouse college, got in touch with UnitedHealth Group early in the pandemic.
The very people who most require solutions to COVID are those who are least likely to be involved in the search to find them.
A colleague he worked with at Grady Hospital in Atlanta was the guy when it came to studying sickle cell disease, a recessive genetic disorder that causes red blood cells to harden into half-moon shapes, causing cardiovascular problems. Sickle cell disease is more common in African Americans than it is in Caucasians, in part because having just one gene for the disease, called sickle cell trait, is protective against malaria, which is endemic to much of Africa. Roughly one in 12 African Americans carry sickle cell trait, and Taylor's colleague wondered if this could be one factor affecting differential outcomes for COVID-19.
UnitedHealth Group granted Taylor and his colleague the money to study sickle cell trait in COVID, and then, as they continued working together, they began to ask Taylor his opinion on other topics. As an insurance company, United had realized early in the pandemic that it was sitting on a goldmine of patient data—some 120 million patients' worth—that it could sift through to look for potential COVID treatments.
Their researchers thought they had found one: In a small subset of 14,000 people who'd contracted COVID, there was a group whose bills were paid by Medicare (which the researchers took as a proxy for older age). The people in this group who were taking ACE inhibitors, blood vessel dilators often used to treat high blood pressure, were 40 percent less likely to be hospitalized than those who were not taking the drug.
The connection between ACE inhibitors and COVID hospitalizations was a correlation, a statistical association. To determine whether the drugs had any real effect on COVID outcomes, United would have to perform another, more rigorous study. They would have to assign some people to receive small doses of ACE inhibitors, and others to receive placebos, and measure the outcomes under each condition. They planned to do this virtually, allowing study participants to sign up and be screened online, and sending drugs, thermometers, and tests through the mail. There were two reasons to do it this way: First, the U.S. Food and Drug Administration had been advising medical researchers to embrace new strategies in clinical trials as a way to protect participants during the pandemic.
The second reason was why they asked Herman Taylor to co-supervise it: Clinical trials have long had a diversity problem. And going virtual is a potential solution.
Since the beginning of the pandemic, COVID-19 has infected people of color at a rate of three times that of Caucasians (killing Black people at a rate 2.5 times as high, and Hispanic and American Indian or Alaska Native people at a rate 1.3 times as high). A number of explanations have been put forth to explain this disproportionate toll. Among them: higher levels of poverty, essential jobs that increase exposure, and lower quality or inadequate access to medical care.
Unfortunately, these same factors also affect who participates in research. People of color may be less likely to have doctors recommend studies to them. They may not have the time or the resources to hang out in a waiting room for hours. They may not live near large research institutions that conduct trials. The result is that new treatments, even for diseases that affect Latin, Native American, or African American populations in greater proportions, are studied mostly in white volunteers. The very people who most require solutions to COVID are those who are least likely to be involved in the search to find them.
Virtual trials can alleviate a number of these problems. Not only can people find and request to participate in these types of trials through their phones or computers, virtual trials also cover more costs, include a larger geographical range, and have inherently flexible hours.
"[In a traditional study] you have to go to a doctor's office to enroll and drive a couple of hours and pay $20 for parking and pay $15 for a sandwich in the hospital cafeteria and arrange for daycare for your kids and take time off of work," says Dr. Jonathan Cotliar, chief medical officer of Science37, a platform that investigators can hire to host and organize their trials virtually. "That's a lot just for one visit, much less over the course of a six to 12-month study."
Cotliar's data suggests that virtual trials' enhanced access seriously affects the racial makeup of a given study's participant pool. Sixty percent of patients enrolled in Science37 trials are non-Caucasian, which is, Cotliar says, "staggering compared to what you find in traditional site-based research."
But access is not the only barrier to including more people of color in clinical trials. There is also trust. When agreeing to sign up for research, undocumented immigrants may worry about finding themselves in legal trouble or without any medical support should something go wrong. In a country with a history of experimenting on African Americans without their consent, black people may not trust institutions not to use them as guinea pigs.
"A lot of people report being somewhat disregarded or disrespected once entering the healthcare system," Taylor says. "You take it all together, then people wonder, well, okay, this is how the system tends to regard me, yet now here come these people doing research, and they're all about getting me into their studies." Not so surprising that a lot of people may respond with a resounding "No thanks."
United's ACE inhibitor trial was notable for addressing both of these challenges. In addition to covering costs and allowing study subjects to participate from their own homes, it was being co-sponsored by a professor at Morehouse, one of the country's historic black colleges and universities (often abbreviated HBCUs). United was recruiting heavily in Atlanta, whose population is 52 percent African American. The study promised a thoughtful introduction to a more egalitarian future of medical research.
There's just one problem: It isn't going to happen.
This month, in preparation for the study, United reanalyzed their ACE inhibitor data with all the new patients who'd contracted COVID in the months since their first analysis. Their original data set had been concentrated in the Northeast, mostly New York City, where the earliest outbreak took place. In the 12 weeks it had taken them to set up the virtual followup study, epicenters had shifted. United's second, more geographically comprehensive sample had ten times the number of people in it. And in that sample, the signal simply disappeared.
"I was shocked, but that's the reality," says Deneen Vojta, executive vice president of enterprise research and development for UnitedHealth Group. "You make decisions based on the data, but when you get more data, more information, you might make a different decision. The answer is the answer."
There was no point in running a virtual ACE inhibitor study if a larger, more representative sample of people indicated the drug was unlikely to help anyone. Still, the model United had established to run the trial remains viable. Even as she scrapped the ACE inhibitor study, Vojta hoped not just to continue United's relationship with Dr. Taylor and Morehouse, but to formalize it. Virtual platforms are still an important part of their forthcoming trials.
If people don't believe a vaccine has been created with them in mind, then they won't take it, and it won't matter whether it exists or not.
United is not alone in this approach. As phase three trials for vaccines against SARS CoV-2 get underway, big pharma companies have been publicly articulating their own strategies for including more people of color in clinical trials, and many of these include virtual elements. Janelle Sabo, global head of clinical innovation, systems and clinical supply chain at Eli Lilly, told me that the company is employing home health and telemedicine, direct-to-patient shipping and delivery, and recruitment using social media and geolocation to expand access to more diverse populations.
Dr. Macaya Douoguih, Head of Clinical Development and Medical Affairs for Janssen Vaccines under Johnson & Johnson, spoke to Congress about this issue during a July hearing before the House Energy and Commerce Oversight and Investigations Subcommittee. She said that the company planned to institute a "focused digital and community outreach plan to provide resources and opportunities to encourage participation in our clinical trials," and had partnered with Johns Hopkins Bloomberg School of Public Health "to understand how the COVID-19 crisis is affecting different communities in the United States."
But while some of these plans are well thought-out, others are concerningly nebulous, featuring big pronouncements but fewer tangible strategies. In that same July hearing, Massachusetts representative Joe Kennedy III (D) sounded like a frustrated teacher when admonishing four of the five leads of the present pharma companies (AstraZeneca, Johnson & Johnson, Merck, Moderna, and Pfizer) for not explaining exactly how they'd ensure diversity both in the study of their vaccines, and in their eventual distribution.
This matters: The uptake of the flu vaccine is 10 percentage points lower in both the African American and Hispanic communities than it is in Caucasians. A Pew research study conducted early in the pandemic found that just 54 percent of Black adults said they "would definitely or probably get a coronavirus vaccine," compared to 74 percent of Whites and Hispanics.
"As a good friend of mine, Dr. [James] Hildreth, president at Meharry, another HBC medical school, likes to say: 'A vaccine is great, but it is the vaccination that saves people,'" Taylor says. If people don't believe a vaccine has been created with them in mind, then they won't take it, and it won't matter whether it exists or not.
In this respect, virtual platforms remain an important first step, at least in expanding admittance. In June, United Health opened up a trial to their entire workforce for a computer game that could treat ADHD. In less than two months, 1,743 people had signed up for it, from all different socioeconomic groups, from all over the country. It was inching closer to the kind of number you need for a phase three vaccine trial, which can require tens of thousands of people. Back when they'd been planning the ACE inhibitor study, United had wanted 9,600 people to agree to participate.
Now, with the help of virtual enrollment, they hope they can pull off similarly high numbers for the COVID vaccine trial they will be running for an as-yet-unnamed pharmaceutical partner. It stands to open in September.
Is there a robot nanny in your child's future?
From ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold. Copyright © 2024 by the author and reprinted by permission of St. Martin’s Publishing Group.
Could the use of robots take some of the workload off teachers, add engagement among students, and ultimately invigorate learning by taking it to a new level that is more consonant with the everyday experiences of young people? Do robots have the potential to become full-fledged educators and further push human teachers out of the profession? The preponderance of opinion on this subject is that, just as AI and medical technology are not going to eliminate doctors, robot teachers will never replace human teachers. Rather, they will change the job of teaching.
A 2017 study led by Google executive James Manyika suggested that skills like creativity, emotional intelligence, and communication will always be needed in the classroom and that robots aren’t likely to provide them at the same level that humans naturally do. But robot teachers do bring advantages, such as a depth of subject knowledge that teachers can’t match, and they’re great for student engagement.
The teacher and robot can complement each other in new ways, with the teacher facilitating interactions between robots and students. So far, this is the case with teaching “assistants” being adopted now in China, Japan, the U.S., and Europe. In this scenario, the robot (usually the SoftBank child-size robot NAO) is a tool for teaching mainly science, technology, engineering, and math (the STEM subjects), but the teacher is very involved in planning, overseeing, and evaluating progress. The students get an entertaining and enriched learning experience, and some of the teaching load is taken off the teacher. At least, that’s what researchers have been able to observe so far.
To be sure, there are some powerful arguments for having robots in the classroom. A not-to-be-underestimated one is that robots “speak the language” of today’s children, who have been steeped in technology since birth. These children are adept at navigating a media-rich environment that is highly visual and interactive. They are plugged into the Internet 24-7. They consume music, games, and huge numbers of videos on a weekly basis. They expect to be dazzled because they are used to being dazzled by more and more spectacular displays of digital artistry. Education has to compete with social media and the entertainment vehicles of students’ everyday lives.
Another compelling argument for teaching robots is that they help prepare students for the technological realities they will encounter in the real world when robots will be ubiquitous. From childhood on, they will be interacting and collaborating with robots in every sphere of their lives from the jobs they do to dealing with retail robots and helper robots in the home. Including robots in the classroom is one way of making sure that children of all socioeconomic backgrounds will be better prepared for a highly automated age, when successfully using robots will be as essential as reading and writing. We’ve already crossed this threshold with computers and smartphones.
Students need multimedia entertainment with their teaching. This is something robots can provide through their ability to connect to the Internet and act as a centralized host to videos, music, and games. Children also need interaction, something robots can deliver up to a point, but which humans can surpass. The education of a child is not just intended to make them technologically functional in a wired world, it’s to help them grow in intellectual, creative, social, and emotional ways. When considered through this perspective, it opens the door to questions concerning just how far robots should go. Robots don’t just teach and engage children; they’re designed to tug at their heartstrings.
It’s no coincidence that many toy makers and manufacturers are designing cute robots that look and behave like real children or animals, says Turkle. “When they make eye contact and gesture toward us, they predispose us to view them as thinking and caring,” she has written in The Washington Post. “They are designed to be cute, to provide a nurturing response” from the child. As mentioned previously, this nurturing experience is a powerful vehicle for drawing children in and promoting strong attachment. But should children really love their robots?
ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold (January 9, 2024).
St. Martin’s Publishing Group
The problem, once again, is that a child can be lulled into thinking that she’s in an actual relationship, when a robot can’t possibly love her back. If adults have these vulnerabilities, what might such asymmetrical relationships do to the emotional development of a small child? Turkle notes that while we tend to ascribe a mind and emotions to a socially interactive robot, “simulated thinking may be thinking, but simulated feeling is never feeling, and simulated love is never love.”
Always a consideration is the fact that in the first few years of life, a child’s brain is undergoing rapid growth and development that will form the foundation of their lifelong emotional health. These formative experiences are literally shaping the child’s brain, their expectations, and their view of the world and their place in it. In Alone Together, Turkle asks: What are we saying to children about their importance to us when we’re willing to outsource their care to a robot? A child might be superficially entertained by the robot while his self-esteem is systematically undermined.
Research has emerged showing that there are clear downsides to child-robot relationships.
Still, in the case of robot nannies in the home, is active, playful engagement with a robot for a few hours a day any more harmful than several hours in front of a TV or with an iPad? Some, like Xiong, regard interacting with a robot as better than mere passive entertainment. iPal’s manufacturers say that their robot can’t replace parents or teachers and is best used by three- to eight-year-olds after school, while they wait for their parents to get off work. But as robots become ever-more sophisticated, they’re expected to perform more of the tasks of day-to-day care and to be much more emotionally advanced. There is no question children will form deep attachments to some of them. And research has emerged showing that there are clear downsides to child-robot relationships.
Some studies, performed by Turkle and fellow MIT colleague Cynthia Breazeal, have revealed a darker side to the child-robot bond. Turkle has reported extensively on these studies in The Washington Post and in her book Alone Together. Most children love robots, but some act out their inner bully on the hapless machines, hitting and kicking them and otherwise trying to hurt them. The trouble is that the robot can’t fight back, teaching children that they can bully and abuse without consequences. As in any other robot relationship, such harmful behavior could carry over into the child’s human relationships.
And, ironically, it turns out that communicative machines don’t actually teach kids good communication skills. It’s well known that parent-child communication in the first three years of life sets the stage for a very young child’s intellectual and academic success. Verbal back-and-forth with parents and care-givers is like fuel for a child’s growing brain. One article that examined several types of play and their effect on children’s communication skills, published in JAMA Pediatrics in 2015, showed that babies who played with electronic toys—like the popular robot dog Aibo—show a decrease in both the quantity and quality of their language skills.
Anna V. Sosa of the Child Speech and Language Lab at Northern Arizona University studied twenty-six ten- to sixteen- month-old infants to compare the growth of their language skills after they played with three types of toys: electronic toys like a baby laptop and talking farm; traditional toys like wooden puzzles and building blocks; and books read aloud by their parents. The play that produced the most growth in verbal ability was having books read to them by a caregiver, followed by play with traditional toys. Language gains after playing with electronic toys came dead last. This form of play involved the least use of adult words, the least conversational turntaking, and the least verbalizations from the children. While the study sample was small, it’s not hard to extrapolate that no electronic toy or even more abled robot could supply the intimate responsiveness of a parent reading stories to a child, explaining new words, answering the child’s questions, and modeling the kind of back- and-forth interaction that promotes empathy and reciprocity in relationships.
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Most experts acknowledge that robots can be valuable educational tools. But they can’t make a child feel truly loved, validated, and valued. That’s the job of parents, and when parents abdicate this responsibility, it’s not only the child who misses out on one of life’s most profound experiences.
We really don’t know how the tech-savvy children of today will ultimately process their attachments to robots and whether they will be excessively predisposed to choosing robot companionship over that of humans. It’s possible their techno literacy will draw for them a bold line between real life and a quasi-imaginary history with a robot. But it will be decades before we see long-term studies culminating in sufficient data to help scientists, and the rest of us, to parse out the effects of a lifetime spent with robots.
This is an excerpt from ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold. The book will be published on January 9, 2024.
Story by Big Think
In rare cases, a woman’s heart can start to fail in the months before or after giving birth. The all-important muscle weakens as its chambers enlarge, reducing the amount of blood pumped with each beat. Peripartum cardiomyopathy can threaten the lives of both mother and child. Viral illness, nutritional deficiency, the bodily stress of pregnancy, or an abnormal immune response could all play a role, but the causes aren’t concretely known.
If there is a silver lining to peripartum cardiomyopathy, it’s that it is perhaps the most survivable form of heart failure. A remarkable 50% of women recover spontaneously. And there’s an even more remarkable explanation for that glowing statistic: The fetus‘ stem cells migrate to the heart and regenerate the beleaguered muscle. In essence, the developing or recently born child saves its mother’s life.
Saving mama
While this process has not been observed directly in humans, it has been witnessed in mice. In a 2015 study, researchers tracked stem cells from fetal mice as they traveled to mothers’ damaged cardiac cells and integrated themselves into hearts.
Evolutionarily, this function makes sense: It is in the fetus’ best interest that its mother remains healthy.
Scientists also have spotted cells from the fetus within the hearts of human mothers, as well as countless other places inside the body, including the skin, spleen, liver, brain, lung, kidney, thyroid, lymph nodes, salivary glands, gallbladder, and intestine. These cells essentially get everywhere. While most are eliminated by the immune system during pregnancy, some can persist for an incredibly long time — up to three decades after childbirth.
This integration of the fetus’ cells into the mother’s body has been given a name: fetal microchimerism. The process appears to start between the fourth and sixth week of gestation in humans. Scientists are actively trying to suss out its purpose. Fetal stem cells, which can differentiate into all sorts of specialized cells, appear to target areas of injury. So their role in healing seems apparent. Evolutionarily, this function makes sense: It is in the fetus’ best interest that its mother remains healthy.
Sending cells into the mother’s body may also prime her immune system to grow more tolerant of the developing fetus. Successful pregnancy requires that the immune system not see the fetus as an interloper and thus dispatch cells to attack it.
Fetal microchimerism
But fetal microchimerism might not be entirely beneficial. Greater concentrations of the cells have been associated with various autoimmune diseases such as lupus, Sjogren’s syndrome, and even multiple sclerosis. After all, they are foreign cells living in the mother’s body, so it’s possible that they might trigger subtle, yet constant inflammation. Fetal cells also have been linked to cancer, although it isn’t clear whether they abet or hinder the disease.
A team of Spanish scientists summarized the apparent give and take of fetal microchimerism in a 2022 review article. “On the one hand, fetal microchimerism could be a source of progenitor cells with a beneficial effect on the mother’s health by intervening in tissue repair, angiogenesis, or neurogenesis. On the other hand, fetal microchimerism might have a detrimental function by activating the immune response and contributing to autoimmune diseases,” they wrote.
Regardless of a fetus’ cells net effect, their existence alone is intriguing. In a paper published earlier this year, University of London biologist Francisco Úbeda and University of Western Ontario mathematical biologist Geoff Wild noted that these cells might very well persist within mothers for life.
“Therefore, throughout their reproductive lives, mothers accumulate fetal cells from each of their past pregnancies including those resulting in miscarriages. Furthermore, mothers inherit, from their own mothers, a pool of cells contributed by all fetuses carried by their mothers, often referred to as grandmaternal microchimerism.”
So every mother may carry within her literal pieces of her ancestors.