Virtual Clinical Trials Are Letting More People of Color Participate in Research
Virtual clinical trials are helping to eradicate logistical barriers to clinical trial participation, though trust is still an issue.
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.
Urinary tract infections account for more than 8 million trips to the doctor each year.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”
MILESTONE: Doctors have transplanted a pig organ into a human for the first time in history
A surgeon at Massachusetts General Hospital prepares a pig organ for transplant.
Surgeons at Massachusetts General Hospital made history last week when they successfully transplanted a pig kidney into a human patient for the first time ever.
The recipient was a 62-year-old man named Richard Slayman who had been living with end-stage kidney disease caused by diabetes. While Slayman had received a kidney transplant in 2018 from a human donor, his diabetes ultimately caused the kidney to fail less than five years after the transplant. Slayman had undergone dialysis ever since—a procedure that uses an artificial kidney to remove waste products from a person’s blood when the kidneys are unable to—but the dialysis frequently caused blood clots and other complications that landed him in the hospital multiple times.
As a last resort, Slayman’s kidney specialist suggested a transplant using a pig kidney provided by eGenesis, a pharmaceutical company based in Cambridge, Mass. The highly experimental surgery was made possible with the Food and Drug Administration’s “compassionate use” initiative, which allows patients with life-threatening medical conditions access to experimental treatments.
The new frontier of organ donation
Like Slayman, more than 100,000 people are currently on the national organ transplant waiting list, and roughly 17 people die every day waiting for an available organ. To make up for the shortage of human organs, scientists have been experimenting for the past several decades with using organs from animals such as pigs—a new field of medicine known as xenotransplantation. But putting an animal organ into a human body is much more complicated than it might appear, experts say.
“The human immune system reacts incredibly violently to a pig organ, much more so than a human organ,” said Dr. Joren Madsen, director of the Mass General Transplant Center. Even with immunosuppressant drugs that suppress the body’s ability to reject the transplant organ, Madsen said, a human body would reject an animal organ “within minutes.”
So scientists have had to use gene-editing technology to change the animal organs so that they would work inside a human body. The pig kidney in Slayman’s surgery, for instance, had been genetically altered using CRISPR-Cas9 technology to remove harmful pig genes and add human ones. The kidney was also edited to remove pig viruses that could potentially infect a human after transplant.
With CRISPR technology, scientists have been able to prove that interspecies organ transplants are not only possible, but may be able to successfully work long term, too. In the past several years, scientists were able to transplant a pig kidney into a monkey and have the monkey survive for more than two years. More recently, doctors have transplanted pig hearts into human beings—though each recipient of a pig heart only managed to live a couple of months after the transplant. In one of the patients, researchers noted evidence of a pig virus in the man’s heart that had not been identified before the surgery and could be a possible explanation for his heart failure.
So far, so good
Slayman and his medical team ultimately decided to pursue the surgery—and the risk paid off. When the pig organ started producing urine at the end of the four-hour surgery, the entire operating room erupted in applause.
Slayman is currently receiving an infusion of immunosuppressant drugs to prevent the kidney from being rejected, while his doctors monitor the kidney’s function with frequent ultrasounds. Slayman is reported to be “recovering well” at Massachusetts General Hospital and is expected to be discharged within the next several days.