An analysis of the demographics of a decade’s worth of vaccine clinical trials has found that Black Americans, Latinos, American Indians, and Alaskan Natives, as well as people age 65 and older, were underrepresented as participants within these studies, though most of the differences, when compared with the U.S. population, were not especially large. Adult women, on the other hand, were found to be overrepresented.
More striking, the researchers said, was that of the 230 trials they examined — encompassing some 220,000 people — more than 40% did not record participants’ race and about 65% did not report their ethnicity.
“This is a massive gap in information, and if we want to improve enrollment in clinical trials and we want to see diversity in clinical trials, we need the data,” said Steven Pergam, a vaccine and infectious disease expert at the Fred Hutchinson Cancer Research Center in Seattle and an author on the paper. “It’s amazing that we don’t have the data.”
The lack of diversity in vaccine trials drew attention last year as several Covid-19 vaccine trials had difficulty enrolling people of color. Watching that struggle unfold as the pandemic devastated the country, and communities of color in particular, spurred Julie Silver, an associate professor of physical medicine and rehabilitation at Harvard Medical School, and her colleagues to investigate how representative vaccine clinical trials have been historically.
“This is the first time that a study has looked at what we’ve done over the past decade in terms of inclusion for vaccine clinical trials,” said Silver. “I thought that would help us to understand what we need to do in the future.”
The findings, published Friday in the journal JAMA Network Open, indicate that racial and ethnic disparities have long plagued vaccine clinical trials and provide insight into the importance of diminishing those gaps going forward.
“This study highlights just how far we have to go when it comes to making sure that vaccines work for everyone, and that many organizations and institutions bear responsibility for the problem,” said Jonathan Jackson, director of the Community Access, Recruitment, and Engagement Research Center at Massachusetts General Hospital and Harvard Medical School, who was not involved in the study.
Last year the researchers scoured ClinicalTrials.gov for vaccine studies completed from July 1, 2011, to June 30, 2020. The trials included vaccines against influenza, human papillomavirus, rotavirus, hepatitis B, meningococcal and pneumococcal bacteria, diphtheria, tetanus, pertussis, and malaria, among other scourges. Covid-19 vaccine trials were still ongoing so they were excluded.
Though all 230 clinical trials reported age and sex, the team found only 134 reported race data and only 79 reported ethnicity data.
“This mirrors the early stages of the Covid-19 pandemic, when we simply did not measure disproportionate infection rates in these long-abused groups,” said Jackson. “Given longstanding inequities in clinical research and care, this level of missing data only underscores the depth and complexity of the diversity problem in clinical trials, and should be a headline in its own right.”
In the 134 trials that did report race, 81 (60.4%) did not include Hawaiian or Pacific Islander participants and 65 (48.5%) did not include American Indian or Alaska Native participants.
In the trials that reported race, white adults made up 78% of all participants, Black adults made up 11%, Asians were 6%, American Indians and Alaska Natives made up 0.4%, and Hawaiian and Pacific Islanders were 0.2%. Where ethnicity was reported, Hispanics and Latinos accounted for 12%.
Compared with their share of the U.S. population in 2011 and 2018, white adults were overrepresented in the trials by about 2 to 4 percentage points.
In contrast, Black adults were underrepresented by about 2 to 3 percentage points. American Indians and Alaska Natives were underrepresented by 0.4 to 0.9 percentage points. And Hispanic and Latino people were underrepresented by about 5 to 7 percentage points.
Asian adults and Hawaiian and Pacific Islanders were enrolled at rates similar to their share of the U.S. population.
“Small inequities are still important inequities,” said Laura Flores, a medical and Ph.D. student at the University of Nebraska Medical Center and lead author on the paper. “We’re doing a genuine disservice to these populations by not reaching out and not keeping records or not including them in trials that might benefit them.”
Jackson said the findings likely undercount the extent of underrepresentation of people of color because the researchers compared enrollment data with census data. It would have been better, he said, to compare enrollment with data that reflect those who are at highest risk for getting the infection being studied. “A truly equitable representation comparison would have revealed the true depth of inequitable recruitment to clinical trials,” he said.
The researchers also reported that enrollment of adults over the age of 65 was low, which was not unexpected given that older people are often excluded from early-stage trials. But to the researchers’ surprise, women were overrepresented, making up about 56% of the participants in the studies they examined, while accounting for about 51% to 52% percent of the population. The team had suspected to find the opposite because, they said, conventionally most clinical trials have been done with adult white men.
“That was a really interesting finding, one that we can’t [explain,]” said Silver.
Going forward, the team said it hopes funding agencies such as the National Institutes of Health, as well as the Food and Drug Administration and the pharmaceutical industry, will take better notice of the racial disparities and put more resources into enrolling diverse populations, especially Black and Latino people, into vaccine and other clinical trials.
“They need to be sure they realize that recruiting minorities is not cheap,” said Carlos del Rio, an infectious disease specialist from Emory University School of Medicine and another author of the study. “The low-hanging fruit is recruiting easy-to-reach participants. The harder to reach populations require more money.”
The researchers said they also hope their study will encourage stronger enforcement of regulations requiring researchers to report race and ethnicity in clinical trials.
“There are some regulations about this, but there’s no teeth to them at the moment,” said Pergam.
In 1993, the NIH Revitalization Act called for the National Institutes of Health to “establish guidelines for the inclusion of women and minorities in clinical research.” The policy was updated in the early 2000s to expand those inclusion guidelines and clarify the reporting guidance for sex, gender, race, and ethnicity. An update in 2017 called for Phase 3 clinical trials to “ensure results of valid analyses by sex/gender, race, and/or ethnicity are submitted to Clinicaltrials.gov.”
“We need to shift that narrative from ‘possibly you should report this’ to a requirement that ‘this is needed,’” Pergam said. “There clearly needs to be a stronger hand pushing this to be done, because if we can’t do it in vaccine trials, then it really does suggest it’s problematic.”