Diversity matters: Inclusivity in clinical trials

Why diversity matters

Vaccines are often designed to be given to large groups of people. The COVID-19 pandemic has taught us that infectious diseases do not stop at borders. This is why it is so important to understand the safety and efficacy of a vaccine in a diverse group of volunteers of varying age, gender, race, health status, and geographic and ethnic origin, because a vaccine can affect different people in different ways.

Ethnicity: Researchers have found that young African Americans, for example, produced different amounts of antibodies (proteins that fight an infection caused by a virus or bacteria) when given an influenza vaccine, compared with Whites and older African Americans.1 Similarly, the immune response to a rubella vaccine was higher in African Americans than in Whites or Hispanics.2 Understanding these differences can help researchers optimize the use of a vaccine to bring more benefits to more people around the world.

Gender: When it comes to gender, the inclusion of women in phase 1 trials in the United States remains low at just 22%.3 It is important to study the effect of a vaccine or drug in women, given that medicines may have a different effect on them compared with men.4 Even though vaccination of pregnant women is also known to be important and beneficial, pregnant women tend to be routinely excluded from these studies for health and safety concerns, but also for ethical reasons.5 While there may be risks, surveys have revealed that many pregnant women would be willing to take part in vaccine trials.6

Age: About 46% of Europeans aged 45 to 54 years receive prescription medicines, rising to 87% for those over 75 years of age.7 Despite these numbers, clinical trials for broad conditions (not age-specific) included just 9% of participants aged 65 years or older, and only 1% of volunteers were aged 75 years or older.8 One of the reasons why studies tend to exclude older adults is that these groups are often considered to be frail. For respiratory diseases, however, which can impact a broad age range, it’s essential that clinical research address age diversity to ensure that drugs or vaccines are safe and effective for all.

Health status and existing medical conditions: Connected to challenges in age group diversity, comorbidity (the presence of two or more health conditions in a person) can be another factor in the exclusion of volunteers from clinical trials. Older volunteers are more often excluded due to having multiple medical challenges for which they require various medical treatments that may risk their safety or interfere with a clinical trial.8 One study that examined clinical trials for their age diversity found that in 75% of trials, comorbidities were the reason for exclusion.8 Another study reported that comorbidity was one of the exclusion criteria in 68% of the examined trials.9 In the real world, patients may have multiple medical conditions or be coprescribed medication. Assessing representatives of these patient populations is vital to ensure medicines work as intended for as many people as possible.

The historical lack of diversity in clinical trials means we are not always getting an accurate picture of the efficacy and safety of innovative new tools in real-world populations. Fortunately, increased commitment from pharmaceutical companies and technological advancements are starting to make a positive difference. Improved access to digital technologies, such as telehealth and video calls, are making it easier to enable participation of people who do not live near trial sites, lowering barriers and expanding the potential increased diversity in trials.10

Diversity in Novavax clinical trials: Novavax is committed to diversity in our clinical trials, in order to detect differences in safety and efficacy among people of different ages, comorbidities, races, ethnicities, and genders.

PREVENT-19, our phase 3 trial conducted in the United States and Mexico, was designed in line with diversity guidance from the FDA.11 We prioritized enrolling underrepresented minorities and people at greater risk of infection with COVID-19, including those with underlying medical conditions and those at higher risk for contracting the disease, that is people living in more crowded or shared housing and essential workers in hospitals, transportation, and farming sectors.12

Of the almost 30,000 participants, 13% were aged 65 years or older.13 Furthermore, 20% of all participants were Hispanic, 12% were African American, 7% were Native American, and 5% were Asian American.13

Historically, Native Americans have had fewer opportunities to participate in clinical trials because of typically poor access to study sites, which are often based in central urban areas. Distrust of the medical community is also a large factor that impacts the potential participation of Native American communities. Some tribes also require several layers of approval for clinical trials, a challenge researchers aren’t always willing to overcome.14 Although these communities have seen some of the highest rates of COVID-19 deaths due to the disease, they have been largely underrepresented in clinical studies.15 By working closely with these communities, the Novavax US phase 3 PREVENT-19 trial was able to recruit approximately 2,000 Native Americans.13

By including underrepresented groups in vaccine trials, we can help shape the future of equitable scientific research.

  1. Kurupati R, et al. Oncotarget. 2016;7:62898−62911.
  2. Mayo Clinic. African-Americans Respond Better to Rubella Vaccine. Available at: https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-discovers-african-americans-respond-better-to-rubella-vaccine/ [Accessed January 2022].
  3. Labots G, et al. Br J Clin Pharmacol. 2018;84:700−707.
  4. United States General Accounting Office. GAO-01-286R Drugs Withdrawn from Market. 2001. Available at: https://www.gao.gov/assets/gao-01-286r.pdf [Accessed January 2022].
  5. Ruth F, et al. Ethics Hum Res. 2020;42(4):17–23 [Accessed January 2022].
  6. Schwartz D. Vaccines. 2018;6:81.
  7. Marum RJ. Brit J Clin Pharmacol. 2020;86:2014−2016.
  8. Beers E, et al. J Am Geriatr Soc. 2014;62:1883−1890.
  9. He J, et al. Trials. 2020;21:228.
  10. ACRO. Technology solutions: Weathering a storm, helping envision a future. Available at: https://www.acrohealth.org/2020/11/16/technology-solutions-weathering-a-storm-helping-envision-a-future/ [Accessed January 2022].
  11. FDA. Center for Drug Evaluation and Research. Enhancing the Diversity of Clinical Trial Populations — Eligibility Cr. U.S. Food and Drug Administration. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enhancing-diversity-clinical-trial-populations-eligibility-criteria-enrollment-practices-and-trial [Accessed January 2022].
  12. Novavax. COVID-19 Vaccine Candidate Trials. Available at: https://www.novavax.com/PREVENT-19 [Accessed January 2022].
  13. Dunkle LM, et al. N Eng J Med. 2022;386:531–543.
  14. Guadagnolo BA, et al. J Health Care Poor Underserved. 2008;20:210–226.
  15. Center for American Indian Health. COVID-19 Pfizer Vaccine Clinical Trial. 2021. Available at: https://caih.jhu.edu/programs/pfizer-covid-19-vaccine-clinical-trial/ [Accessed January 2022].
Additional reading

Additional reading

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Recombinant, protein-based nanoparticle vaccine technology

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