Most racial and ethnic minorities and adults 65 years and older have been underrepresented in U.S. vaccine clinical trials over the last decade, while women have been overrepresented, according to a study published in JAMA Network Open in February.
More importantly, researchers discovered that a large percentage of trials reported no data on the race or ethnicity of their participants, despite federal guidelines and recommendations, which have set minimum standards for inclusion of diverse populations in clinical trials.
“Anytime we have chronic underrepresentation of any given population, we’re not going to understand the medical needs and how the proposed treatments will work for that population,” says one of the study’s authors, Dr. Julie K. Silver. “And it’s important to recognize that this sometimes comes down to physiological differences. For example, in women versus men. Or in someone who is older, whose kidneys may work differently than someone who’s 20 years old.”
The authors looked at 230 vaccine clinical trials conducted in the U.S. between July 2011 and June 2020. Ongoing vaccine trials, including COVID-19, were excluded. A total of 219,555 adults and children participated in them. Forty two percent of the trials didn’t report race and 66% didn’t report ethnicity on ClinicalTrials.gov, a database of privately- and publicly-funded clinical studies conducted worldwide.
“We don’t know if they collected the data and just didn’t report it on ClinicalTrials.gov,” says Silver, an associate professor and associate chair of the Department of Physical Medicine and Rehabilitation at Harvard Medical School. “So it’s missing from ClinicalTrials.gov, where it’s supposed to be reported.”
The study, “Assessment of the Inclusion of Racial/Ethnic Minority, Female, and Older Individuals in Vaccine Clinical Trials,” adds to the body of evidence that participants of most clinical trials are not truly representative of the general population, leaving gaps in understanding health disparities and increased burden of diseases.
Silver and her colleagues write that improving racial and ethnic diversity in vaccine trials is important because it might be associated with improved vaccination rates among minority groups. “Efforts to improve inclusion may help to address vaccine hesitancy, provide education, and counter safety concerns about vaccines by ensuring equitable representation in definitive clinical trials,” they write.
For the new study, the team compared the demographic makeup of vaccine trial participants against the U.S population data from 2011 and 2019 American Community Surveys from the U.S. Census Bureau. They find that Black, Hispanic or Latino, American Indian, Alaska Natives and older adults were underrepresented in vaccine trials.
Among the adult clinical trials that reported participants’ race, 78% of participants were white people, who comprise 76% of the U.S. population. Black people make up 14% of the U.S. population but 11% of vaccine trial participants. Adults identified as American Indian or Alaska Native make up 0.4% of participants, compared with 1.3% of the U.S. population.
In adult trials that reported ethnicity, fewer than 12% of participants identified as either Hispanic or Latino. Meanwhile, census data show 19% of adults living in the U.S. identify as Hispanic or Latino.
The groups well represented in adult vaccine trails were Asians and Native Hawaiian or Pacific Islanders, the analysis finds.
The analysis also shows that among adult clinical trials, 45% recruited adults 65 years and older age group and 40% enrolled participants 65 years or older. Among 170 trials reporting participants’ age, 12% of participants were age 65 or older — 4 percentage points lower than the U.S. population.
In pediatric trials, Black children made up 10% of participants and Hispanic children made up 23%. Census data show 14% of American children are Black and 25% are Hispanic or Latino.
Researchers were surprised to learn that women were overrepresented, Silver says.
Women, who accounted for 56% of trial participants, make up about 51% of the U.S. population, according to census data.
“Most prior studies — not all — have shown underrepresentation of women in clinical trials,” Silver says. “Though that’s not universally the case, that tends to be more common than either equitable inclusion or overrepresentation.”
The researchers didn’t look into what could be driving the overrepresentation of women in vaccine trials. Silver says one possibility is that some clinical trials recruit in pediatricians’ offices and moms often are the parent bringing children to appointments.
“We certainly can’t determine whether that’s true or not, or whether that’s influencing the results,” Silver says.
The “2015-2019 Drug Trials Snapshots Summary Report,” published in November 2020 by the U.S. Food and Drug Administration, also shows women were overrepresented in clinical trials.
That report, which covers a variety of clinical trials – not just vaccines — with a combined 292,766 adult participants worldwide between 2015 and 2019, finds that 56% of participants were women.
Globally, women represent 51% of the clinical participants, the FDA report shows.
Diversity in COVID-19 vaccine trials
Data from the three COVID-19 vaccine clinical trials, meanwhile, paint a different picture.
Women are underrepresented in Pfizer, Moderna and Johnson & Johnson clinical trials, while the percentage of minority groups varies by each company’s trial.
A January report by the Kaiser Family Foundation, “Racial Diversity within COVID-19 Vaccine Clinical Trials: Key Questions and Answers,” compares the participant make up of Pfizer and Moderna vaccines, pointing out that diversity in COVID-19 vaccine trials is an important topic because the pandemic has taken a disproportionate toll on people of color.
“Diversity within clinical trials for a COVID-19 vaccine helps ensure safety and effectiveness across populations and may increase confidence in getting the vaccine among people of color,” the authors write.
The report shows that, compared with the Census Bureau’s 2019 American Community Survey data, whites were overrepresented in both Pfizer and Moderna COVID-19 vaccine trials, while Black and Asian participants were underrepresented. American Indian/Alaska Natives and Native Hawaiian or Other Pacific Islanders were equally represented. Hispanic participants were overrepresented, compared with the general population.
“These data show that although people of color are underrepresented in the clinical trials for the two initial COVID-19 vaccines compared to their share of the population, the trials include people from diverse racial/ethnic backgrounds and are more diverse than some trials have historically been,” the authors write.
The Johnson & Johnson vaccine trial data, which were released after KFF’s report, show Black, Hispanic and American Indian or Alaska Native participants were overrepresented compared with the 2019 census data. Asian participants were underrepresented, while Native Hawaiian or other Pacific Islanders were equally represented.
Recommendations to diversify clinical trials
There are several reasons why people of color are underrepresented in clinical trials.
For one, according to the Kaiser Family Foundation report, fewer clinical trials are available at hospital systems where people of color are more likely to receive care. Lack of information and historical and ongoing racism and discrimination are among other contributors, the report says.
Researchers have made greater efforts in recent years to increase diversity in clinical trials.
Both the FDA and National Institutes of Health have made recommendations and guidelines for data collection and inclusion of diverse populations in clinical trials.
In 2001, the National Institutes of Health updated its policy to provide a minimum standard of inclusion for sex, gender and racial and ethnic minority groups in Phase 3 clinical trials, which is one of the final phases of research, showing safety and efficacy of the drug on the study participants. In 2017, it announced an amendment requiring investigators to submit trial results for these specific groups to ClinicalTrials.gov.
“Findings suggest that NIH policies on reporting of identified groups have increased over time, but a need to focus such policies beyond reporting to representative enrollment remains,” Silver and her colleagues write, recommending investments by federal agencies and industry to ensure enrollment is fair and equitable.
There are other efforts to improve diversity among research participants.
The National Academies of Sciences, Engineering, and Medicine recently set up an ad hoc committee to “undertake a study examining the long-term economic and medical impacts of the lack of inclusion of women and underrepresented minority groups in clinical research and subsequent translational work.”
In late February, the NIH launched an initiative called UNITE, aimed at ending structural racism and racial inequities in biomedical research.
“Our intention is to apply what we learn from this initiative to all future actions centered on diversity, equity, and inclusion for other groups who have been marginalized,” the director of the Dr. Francis Collins, writes in a blog post on the institute’s website. “Our resolve must be unflinching – it must not waver in the face of difficulties or tire at the magnitude of the problem.”
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