These days clinical trials are a global endeavor spanning 204 countries, according to Home – ClinicalTrials.gov (1), something that should make accusations of racial bias harder to substantiate. However, the crux of the matter is who participates in clinical trials within a given country.
- Diversity mandates do little when mechanisms to enforce them are left unstated. In such a vacuum, individual biases and structural barriers drive the process.
- The US has a bleak history of unethical medical experimentation on minorities that has left them with a persistent and deep mistrust of the medical establishment.
- Meantime, being largely white, US clinical trial organizers don’t reflect the ethnic diversity of the population at large. Such a decision-making silo inadvertently de-prioritizes clinical trial recruitment of minorities.
Diversity mandates do little when mechanisms to enforce them are left unstated
After clinical trials became the norm for new drug approvals post- WWII, white males remained over-represented in them for several decades. In response, the US National Institutes of Health Revitalization Act of 1993 mandated women and minorities be represented in NIH-funded research. Enforcing a mandate is easier said than done especially when mechanisms to do so are left unstated. Not surprising then that biases and structural barriers take hold and drive the process in such a vacuum.
- As recently as 2015, though blacks and Latinos make up ~30% of the US populations, a study found they accounted for just ~6% of participants in federally funded clinical trials (2).
- Another US study found <2% of cancer clinical trials focused on the health needs of racial/ethnic minorities (3).
- Even though African Americans are >30% more likely to have asthma and even >3X more likely to die from it, a study found <5% of federally funded lung disease studies in the US focused on them between 1993 and 2013 (4).
- Even Precision medicine – Wikipedia, the notion that medical treatment could be tailored to an individual’s variations in genes, environment and lifestyle, leaves minorities far behind. As of 2011, ~96% of participants in >1000 Genome-wide association study – Wikipedia (GWAS) were of European descent (5).
- Since some minorities tend to be poorer and to live in places far from large reputed medical centers that conduct clinical trials, practical constraints such as time and money needed to travel to a study site may hamper their participation.
- Diversity mandates on federally funded trials don’t apply to the pharmaceutical industry which is today the biggest funder of clinical trials. For such trials, only something like a diversity mandate enforceable by the FDA during its review process of product approval could make a dent (6).
The US has a bleak history of unethical medical experimentation on minorities that has left them with a persistent and deep mistrust of the medical establishment
In the US, the Tuskegee syphilis experiment – Wikipedia looms large in collective consciousness as a constant reminder of the lengths to which racial animus could infect a clinical study design in that the study doctors knowingly and wantonly withheld treatment from syphilis-infected poor, uneducated, rural black men not for a year or two but for a whopping 40 years. Any wonder then that studies (7, 8) continue to find the African American community mistrust of the medical establishment?
Given such a bleak history, where African Americans are concerned, racial bias in US clinical trial enrollment is best viewed as a two-way street with low black (and other minority) participation explainable two ways,
- one, implicit bias of trial researchers may play a considerable role in restricting minority enrollment. Some recent studies found a profound degree of implicit bias in medical doctors on matters of race. It stands to reason to assume such bias might well bleed into clinical trial enrollment processes as well.
- A 2016 study found substantial numbers of white medical students continue to hold false beliefs about biological differences between black and white people, (see below from 9),
‘blacks have thicker skin than do white people or that black people’s blood coagulates more quickly than white people’s blood.’
- Another 2016 study found (see below from 10, emphasis mine),
‘…significant racial-ethnic disparities, with non-Hispanic Blacks being less likely (adjusted odds ratio ranging from 0.56–0.67, p value < 0.05) to receive opioid prescription at discharge during ED visits for back pain and abdominal pain, but not for toothache, fractures and kidney stones, compared to non-Hispanic whites after adjusting for other covariate.’
- Indeed, such implicit bias has been used to explain the far lower rates of prescription opioid abuse among African Americans and Hispanics in the early years of the ongoing opioid crisis (11, 12).
- two, blacks, especially black males, have for long actively avoided participating in clinical trials due to their understandable deep-rooted mistrust of the medical establishment (7, 8). Some other minorities also avoid them due to lingering mistrust engendered by a past history of trust abuse.
- Apparently so hard-wired is this mistrust that as recently as 2014, a severe TB outbreak in the small rural Alabama town of Marion went unchecked because those affected chose not to go to a doctor (13).
- Bad acts and actors in US biomedical research didn’t magically end with Tuskegee. In 1989, Arizona State University researchers collaborated with the Havasupai Tribe on a type II diabetes project. In 2003, Carletta Tiousi, a trial participant, found out that blood samples taken during this trial had been used without her and other participants’ consent for testing schizophrenia, migration and inbreeding (14). A lawsuit led to an out of court settlement and the tribe members received funds for a school and clinic, and return of their samples.
Being largely white, clinical trial organizers don’t reflect the ethnic diversity of the population at large. Such a decision-making silo inadvertently de-prioritizes recruitment of minorities
Minority participation in US clinical trials could be increased through concerted effort on fairly simple, practical steps (15, 16, 17, 18, 19),
- Situate clinical trials where minorities tend to live.
- Provide low income participants travel assistance back and forth to trial sites.
- Focus on recruitment efforts in places such as churches and barbershops where minorities tend to congregate.
- Employ minority recruitment staff to serve as outreach partners to engage with potential minority participants in their own languages.
- Advertise clinical trials within ethnic communities using culturally appropriate informational material clarifying purpose of the trial, and how data will be collected and used.
Nothing new about any of these suggestions. They’ve floated around for years and yet little changes. Bias in clinical trial recruitment, as in any aspect of human life, need not always occur deliberately. They can and often are the result of blinkered thinking that easily takes root in silos. When a particular majority has the power, the decisions it makes reflect that.
Minority researchers would be more likely to focus on issues of health disparities in minority populations and yet even after controlling for other variables such as education, training and experience, one study found that they were ~half as likely to get NIH grants (20).
Racially homogenous make-up of clinical trial participants reflect the racially homogenous make-up of clinical trial decision makers. Seats at the table; changes in clinical trial participants will occur lockstep with changes in clinical trial organizers, when trials are conducted not by largely white doctors but by a healthy mix of white, black, Hispanic and other minority doctors who better represent their distribution in the US population at large.
1. Studies on Map – ClinicalTrials.gov
2. Oh, Sam S., et al. “Diversity in clinical and biomedical research: a promise yet to be fulfilled.” PLoS medicine 12.12 (2015): e1001918. http://journals.plos.org/plosmed…
3. Chen, Moon S., et al. “Twenty years post‐NIH Revitalization Act: Enhancing minority participation in clinical trials (EMPaCT): Laying the groundwork for improving minority clinical trial accrual.” Cancer 120.S7 (2014): 1091-1096. Twenty years post‐NIH Revitalization Act: Enhancing minority participation in clinical trials (EMPaCT): Laying the groundwork for improving minority clinical trial accrual – Chen – 2014 – Cancer – Wiley Online Library
4. Burchard, Esteban G., et al. “Moving toward true inclusion of racial/ethnic minorities in federally funded studies. A key step for achieving respiratory health equality in the United States.” American journal of respiratory and critical care medicine 191.5 (2015): 514-521. https://www.atsjournals.org/doi/…
5. Bustamante, Carlos D., M. Francisco, and Esteban G. Burchard. “Genomics for the world.” Nature 475.7355 (2011): 163. https://www.igb.illinois.edu/sit…
6. Wilder, Julius M. “Scientific and Ethical Considerations for Increasing Minority Participation in Clinical Trials.” (2018). https://cdn.intechopen.com/pdfs/…
7. Alsan, Marcella, and Marianne Wanamaker. “Tuskegee and the Health of Black Men.” The Quarterly Journal of Economics 133.1 (2017): 407-455. https://economics.stanford.edu/s…
8. Wong, Kristin X. “The Pivotal Role that Race Plays in Medical Research: The Tuskegee Syphilis Study.” (2018). https://pdxscholar.library.pdx.e…
9. Hoffman, Kelly M., et al. “Racial bias in pain assessment and treatment recommendations, and false beliefs about biological differences between blacks and whites.” Proceedings of the National Academy of Sciences 113.16 (2016): 4296-4301. http://www.pnas.org/content/pnas…
10. Singhal, Astha, Yu-Yu Tien, and Renee Y. Hsia. “Racial-ethnic disparities in opioid prescriptions at emergency department visits for conditions commonly associated with prescription drug abuse.” PLoS One 11.8 (2016): e0159224. http://journals.plos.org/plosone…
11. Meghani, Salimah H., Eeeseung Byun, and Rollin M. Gallagher. “Time to take stock: a meta-analysis and systematic review of analgesic treatment disparities for pain in the United States.” Pain Medicine 13.2 (2012): 150-174. https://academic.oup.com/painmed…
12. Finding Good Pain Treatment Is Hard. If You’re Not White, It’s Even Harder.
13. In Rural Alabama, a Longtime Mistrust of Medicine Fuels a Tuberculosis Outbreak
14. Havasupai Tribe and the lawsuit settlement aftermath
15. Galsky, Matthew D., et al. “GEographic accessibility to clinical trials for advanced cancer in the United States.” JAMA internal medicine 175.2 (2015): 293-295. Accessibility to US Clinical Trials for Cancer
16. Tanner, Andrea, et al. “Communicating effectively about clinical trials with African American communities: A comparison of African American and White information sources and needs.” Health promotion practice 17.2 (2016): 199-208. https://www.researchgate.net/pro…
17. Wallington, Sherrie F., et al. “Enrolling minority and underserved populations in cancer clinical research.” American journal of preventive medicine 50.1 (2016): 111-117. https://www.ncbi.nlm.nih.gov/pmc…
18. Konkel, Lindsey. “Racial and ethnic disparities in research studies: the challenge of creating more diverse cohorts.” Environmental health perspectives 123.12 (2015): A297. https://www.ncbi.nlm.nih.gov/pmc…
19. Graham, Louis F., et al. “Outreach Strategies to Recruit Low-Income African American Men to Participate in Health Promotion Programs and Research: Lessons From the Men of Color Health Awareness (MOCHA) Project.” American journal of men’s health (2018): 1557988318768602. http://journals.sagepub.com/doi/…
20. Ginther, Donna K., et al. “Race, ethnicity, and NIH research awards.” Science 333.6045 (2011): 1015-1019. Race, Ethnicity, and NIH Research Awards