In the southern US, Matt Maxwell has been working for months to recruit participants for ongoing Covid-19 vaccine trials. As the chief executive officer of Accel Clinical Services, a private clinic that runs trials in Georgia, Florida, and Alabama, he’s used to the logistical difficulty of assembling thousands of people across hundreds of miles. With these trials, though, he’s running into a new challenge.
“I’ve never had a study where someone calls and says we need three more Hispanic patients today,” says Maxwell. “And we’re having those kinds of calls now.”
He’s not the only one. After an influx of white participants in its vaccine trial, pharmaceutical company Moderna told Sharon Smith, vice president of recruiting at the Jacksonville Center for Clinical Research in Florida, to only recruit participants who are Black and Latinx, she says.
The virus has disproportionately affected African American, Latinx, and Native American communities within the US, yet the early stages of recruitment for vaccine trials saw overwhelmingly white participants. That homogeneity is a major obstacle for the testing, approval, and potential use of a vaccine.
In response, Anthony Fauci, director of National Institute of Allergy and Infectious Diseases (NIAID), called on pharmaceutical companies to enroll Black or African American, Latinx, American Indian, and Alaskan Native populations at roughly double their population percentages, or 66.4% of total participants. That representation is essential to garner trust in any approved vaccine, since race and ethnicity can play a role in vaccine responses.
But the industry behind many vaccine trials is ill-equipped to answer that call. Both Maxwell and Smith said the Covid-19 vaccine trials mark the first time pharmaceutical companies have instructed them to enroll racially diverse participants.
Pharmaceutical companies’ struggle to recruit diverse participants to test potential Covid-19 vaccines reflects broader business interests that reinforce racial bias. The industry has long failed to prioritize enrollment of minority groups, instead creating financial incentives for recruitment clinics that emphasize speed at the expense of diversity.
Addressing those long-standing biases is critical to conducting any high-quality vaccine study. The work is time-intensive and, having failed to prioritize diversity until now, many organizations running clinical trials are struggling to change their practices under pressure.
A first time for everything
When pharmaceutical companies study drugs or vaccines, they don’t recruit participants themselves. Instead, they turn to academic centers and private clinics that are practiced at attracting participants and running clinical trials. Typically, a company will hire a contract research organization (CRO), which then draws up contracts with dozens or hundreds of trial sites.
These private clinics are hired on their ability to recruit large numbers of participants quickly and efficiently.
Pharmaceutical corporations running trials pay private clinics an upfront fee to cover administrative costs of recruiting participants, and an additional fee per patient enrolled. A standard budget for a vaccine trial is $10,000 to $15,000 per trial participant, says Maxwell, the bulk of which is spent on the costs of running a trial, but with 10% to 20% profit over the course of a two-year study.Every patient we don’t enroll, another clinic is going to enroll.
Recruitment is time-consuming and expensive, and the fees are designed to encourage enrollment as quickly as possible. Maxwell’s company, Accel Clinical Services, is helping recruit participants for Pfizer, Moderna, and Novovax’s vaccine trials. “It’s competitive enrollment,” he says. “Every patient we don’t enroll, another clinic is going to enroll.”
Financial pressures are less intense for academic institutions. “Many private clinics are driven by the financial interest,” says Jay Vadgama, vice president for research and health affairs at Charles R. Drew University of Medicine and Science, who has run several clinical trials with a focus on underrepresented and under-resourced communities. “Our salaries don’t depend on that kind of revenue.” Instead, he says, pharmaceutical companies pay funds to a university account for education, training, and general expenses, rather than direct compensation for those running the trial.
Among for-profit clinics, the competition incentivizes recruitment of patients who are easy to enroll quickly. In the US, where Black participants make just up 5% of clinical trials and Hispanic participants 1%, the first people to show up are predominantly white. “We’ve had an overwhelming response. Most of them being white Caucasians,” says Smith, who is recruiting participants for Moderna, Pfizer, and Novovax’s Covid-19 vaccine trials.
These clinics may have some experience recruiting different demographic groups. Sometimes, clinical trials are focused only on a particular group, says Smith, noting her clinic helped enroll participants in a study of heart failure among African Americans. But the Covid-19 vaccine trials are the first time a pharmaceutical company has asked her to recruit a demographically representative sample.We’ve had an overwhelming response. Most of them being white Caucasians.
Maxwell agrees: “These vaccine studies are the first time I’ve seen them requiring us to match our racial makeup to our county where we’re located,” he says. Most of the time, recruitment ignores race. “It hasn’t been in the forefront of people’s minds because for us, patients are patients and it’s more about what medical condition you have.”
Diverse recruitment takes more than willingness to enroll participants of all races. In a country where the healthcare system has long disenfranchised certain groups, white people will continue to be overrepresented in clinical trials unless inequalities are explicitly addressed.
How vaccine recruitment contributes to inequality
When clinics are incentivized to recruit participants quickly, without considering diversity, they tend to attract people with flexible schedules. Clinical trials are time-consuming: Participants come in for an initial assessment that can take hours, and multiple follow-up appointments. That means people with less flexible, blue-collar jobs are less likely to enroll. In the US, African Americans, Hispanics, and American Indians are more likely to hold these jobs than non-Hispanic white people.
“Patients that have access to reliable transportation, the ability to take time off to do visits without risking losing their job, patients that have less responsibilities in their life in general—those participants will find it easier to participate in a research trial,” says Maxwell.A lot of our communities don’t have the transportation to go to a clinical site or clinical trial.
Transportation infrastructure in the US is also weaker for those in poorer neighborhoods and, though some pharmaceutical companies pay for the cost of an Uber or Lyft to study sites, this is not standard. “A lot of our communities don’t have the transportation to go to a clinical site or clinical trial,” says Vadgama. Vladimir Berthaud, an internal medicine doctor at Meharry Medical College who is recruiting participants for Novovax’s Covid-19 vaccine, agrees: “Especially in the south, transportation is a must.”
Many clinical trials also require participants to own smartphones, which are used for long-term monitoring. Though some trials provide phones to participants, Maxwell says plenty exclude participants who don’t have their own. As Black, Hispanic, American Indian, and Alaska Native populations are significantly more likely to experience poverty in the US, these barriers to access can further skew racial demographics in trials.
Some racial minorities in the US may also avoid clinical trials because of justified mistrust in the country’s medical system, which has long excluded and abused patients of color. Notorious historical experiments such as the Tuskegee study, in which Black men in Alabama with syphilis were lied to and left to die, contribute to a fear of clinical research. “There’s a lot of skepticism in general against clinical trials, vaccines, the healthcare system, and government in the Black community,” says Berthaud. “That’s been there for generations.”
Over time, biases toward more affluent white participants accumulate and reinforce themselves. Private clinics build up databases of participants from previous trials and use these records for ongoing recruitment, cementing previous demographic inequalities.
Those databases are also filled by patients who were referred to trials by their physicians. But majority African American neighborhoods are 67% more likely to have a shortage of primary care doctors than white neighborhoods, and Vadgama says many physicians are not trained to intentionally refer diverse participants. “There are many, many physicians out there who are practicing in the real world and don’t talk to patients of color to say, by the way, you should consider getting onto a clinical trial,” he says.
Trial recruitment centers themselves must also be more diverse to recruit nationally representative participants, says Berthaud: “Most clinical trial centers are in predominantly white majority institutions.”
The pressure to improve, quickly
The status quo of trial recruitment was not good enough for Covid-19 vaccine trials. “Previously most clinical trials just focused on number [of participants],” says Berthaud. “With coronavirus this is a very different ballgame. This is happening in a very specific context of overt social injustice, racial disparities, and a troubled political atmosphere. That puts pressure on the pharmaceutical companies to get it right.”This is happening in a very specific context of overt social injustice, racial disparities, and a troubled political atmosphere.
There are some immediate changes to address accessibility. To help make it easier for working class participants with less flexible schedules to enroll, for example, Maxwell opened clinics on weekends. Pfizer says it’s providing smartphones to participants who don’t have their own.
But after decades of failing to prioritize diversity, quickly changing the makeup of clinical trials is far from easy. Fixing these problems takes concerted effort over time.
“One advantage we have is the fact we’ve been in these communities for many years,” says Berthaud. Medical researchers at Meharry Medical College, a historically Black college, have worked to earn the trust of local African American physicians and trial participants. “We have a good rapport with medical providers. When medical providers advise on joining a medical trial, they listen.”
Many academic institutions have programs explicitly designed to address racial inequalities, says Vadgama. Charles R. Drew University, for example, was founded to address the lack of medical access in areas of southern Los Angeles with predominantly African American and Latinx populations. “CROs are aware of who we are, where we are, and what kind of communities we represent. They’re interested in collaborating with us because they know we can bring those communities to the table,” he says.
Alejandro Cané, Pfizer’s scientific and medical lead for vaccines in North America, says one solution is to partner with organizations that have close ties to different communities, such as the Black Nurses Association and National Hispanic Caucus of State Legislators. “We’re working in partnership with associations that are very important for those communities,” he says. “It’s not only Pfizer or the [principal investigator] but the local organization that’s very important for the community.”
Pfizer also carefully chose clinics in Arizona, Florida, New York, North Carolina, and Texas where there are large Black, Latinx, and Native American populations, says Cané. “For me, it’s a combination of trust and location.”
Though diversity is improving, progress is slow. Black Americans made up 7% of Moderna’s trial participants as of Sept. 17, and around 34.5% of participants as of Oct. 9 are from diverse communities, defined as participants who are Black, Asian, American Indian or Alaska Native, Hispanic or Latinx, Hawaiian or other Pacific Islander. A company spokesperson said it would provide a breakdown of total diversity per race once enrollment is complete. AstraZeneca did not respond to requests to provide data on diversity within its Covid-19 vaccine trials.https://datawrapper.dwcdn.net/sNYdJ/1/
Meanwhile, Pfizer increased its sample size to from 30,000 to 44,000 in a bid to recruit more participants from minority groups. The company has made diversity data public, showing that 29% of US participants and 43% of global participants are from diverse backgrounds. Rather than aiming for the diversity targets outlined by Fauci, a Pfizer company spokesperson said the company’s goal is to have 30% minority participation—defined as Asian, Black, Hispanic/Latinx, or Native American—within US trials, and 40% globally.
Racially diverse research is essential to understand the impact of vaccines and treatments on all demographics. But clinical trials are also a medical benefit in their own right. “If I told you there was a more effective form of insulin but it was disproportionately available to Caucasian people, I think that would upset a lot of people,” says Maxwell. “Clinical trials that can extend people’s lives or improve their quality of life deserve that same level of scrutiny. They deserve to operate under that same principle that access should be well distributed, fair, and representative of society.”