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# Ensuring Inclusive Representation in Covid-19 Research Trials

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Chapter 1: The Importance of Diversity in Vaccine Trials

It is widely acknowledged by experts that adequate representation of people of color in coronavirus vaccine and drug trials is crucial. However, there is uncertainty regarding whether this is currently being achieved.

The notorious Tuskegee Syphilis Study stands as a stark reminder of the ethical failures in biomedical research in the U.S. Initiated in 1932 during the Great Depression, this study aimed to justify funding for treatment programs aimed at Black Americans suffering from syphilis. The U.S. Public Health Service enlisted 600 Black men in Alabama, 399 of whom were already infected. They were misled into believing they were receiving treatment for "bad blood," a term commonly used at the time for various health issues, while they were denied proper care.

The true purpose of the study—documenting the effects of untreated syphilis—was never disclosed to the participants. Initially set to last just six months, it extended over four decades. By the time it was halted in 1972 due to a public outcry and an Associated Press investigation, researchers had known for over 30 years that penicillin was an effective treatment. Unfortunately, the men involved were never given this option, leading to numerous deaths from the infection or related complications, and many unknowingly transmitted the disease to their partners and children.

The painful legacy of the Tuskegee Study contributes to the ongoing distrust that Black Americans and other marginalized groups have towards medical research. Nearly 50 years after its conclusion, Black Americans represent just 5% of clinical trial participants, despite making up 12% of the U.S. population.

Ruqaiijah Yearby, JD, MPH, a law professor and executive director at the Saint Louis University Institute for Healing Justice and Equity, states, "Historically, participation has been low for racial and ethnic minorities, and I think the legacy of [the] Tuskegee [Syphilis Study] is a part of that." Yearby also highlights more recent exploitative practices in clinical trials that have deepened this distrust.

Section 1.1: Current Representation in Clinical Trials

According to a Pew Research Center poll conducted on June 4, Black Americans exhibit greater skepticism towards medical professionals and experimental treatments than many other racial or ethnic groups, which contributes to lower enrollment in vaccine trials. Structural barriers and researcher biases further exacerbate this issue. A 2011 study by the Society for Women's Health Research and the FDA revealed that while Black Americans account for 12% of the population, they only constitute 5% of clinical trial participants. The disparity is even more pronounced for Hispanics, who make up 16% of the population but only 1% of trial participants.

Given that Black Americans are approximately five times more likely to succumb to Covid-19 compared to whites, and Hispanics about four times more likely, the lack of representation in research targeting SARS-CoV-2 could hinder the effectiveness of drug development for these groups.

On July 14, the New England Journal of Medicine reported on phase 1 results for Moderna's mRNA vaccine, developed with support from the National Institute of Allergy and Infectious Diseases (NIAID). The trial, which included 45 participants, showed promising immune responses, yet only two were Black and six identified as Hispanic or Latino, with the remaining 40 being white. A spokesperson for NIAID noted that recruitment reflected those who responded to the call, but highlighted plans for increased inclusivity in future trials.

Subsection 1.1.1: The Need for Diverse Trials

Diverse representation in clinical trials

Section 1.2: Challenges to Inclusivity

Some other research initiatives have demonstrated better inclusivity. A preliminary study on the antiviral drug remdesivir, published on May 22 in NEJM, included over 1,000 hospitalized Covid-19 patients, with approximately 21% identifying as Black and 23% as Hispanic—figures that better reflect U.S. demographics.

Experts agree that as clinical trials advance into larger phases, diversity in participants will be essential. Although efforts are underway to ensure inclusivity, the effectiveness of these measures remains uncertain.

Chapter 2: The Significance of Inclusive Research

Participation in clinical trials can provide access to potentially life-saving treatments for participants. For instance, those involved in SARS-CoV-2 vaccine trials may gain immunity, while treatment trials could be lifesaving.

The rationale for inclusivity in trials is clear: excluding or underrepresenting certain groups denies them access to critical medical advancements. As Yearby states, "If you're not doing research on a diverse population, then you don't know how it's going to be safe and effective across a diverse population."

A 2015 review by the FDA found that nearly 20% of newly approved drugs displayed different efficacy or safety profiles based on race or ethnicity. This discrepancy can arise from varying prevalence of metabolic diseases among different groups. Factors such as age, sex, and ancestry may also influence treatment outcomes.

Michael from Walter Reed emphasizes the need for trials to reflect the demographics of those most affected by Covid-19. "We don't want studies where the community at risk and the community being tested are different."

Fisher, a social medicine professor, highlights biases in recruitment strategies that can deter minority participation. She points out that trials often cater to those with more flexible schedules and may be located far from public transport, further complicating access for disadvantaged groups.

While some pharmaceutical companies are acknowledging the need for diversity in their studies, achieving this goal remains complex. Pfizer’s Jerica Pitts notes their commitment to studying in diverse communities, using data to identify areas with higher rates of Covid-19 infections.

The success of these strategies may be supported by existing evidence. A 2013 study found no racial or ethnic underrepresentation in trials involving lung injury patients, attributing this success to the focus on diverse population centers.

Creating a Framework for Engagement

Experts agree that "community engagement" is vital for ensuring diverse representation in Covid-19 trials. This concept involves including members from various communities in the planning and implementation phases of research.

"People who are underrepresented or marginalized need to be brought into the fold throughout the process," asserts Charmaine Royal, a professor at Duke University. Many marginalized individuals are willing to participate but often aren't approached.

Michael notes that the lessons learned from the AIDS epidemic regarding community engagement should inform current practices. He stresses the importance of ensuring that those with in-group knowledge are involved in trial design and recruitment.

Early in the pandemic, the rapid pace of research outstripped appropriate engagement efforts, but there has been progress. The establishment of the Covid-19 Prevention Network has been a significant step forward.

Ultimately, the effectiveness of these efforts will be measured by the demographic data from trial enrollments. If disparities continue, adjustments will need to be made to achieve equitable participation.

As of now, it remains uncertain whether these initiatives will yield the desired outcomes.

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