Biomarker Studies, Clinical Trials, & Racial Disparities: What the FDA Recommends
The influence of race on disease etiology is not a novel concept but one that has been hotly debated for years. Is biological race an imaginary concept and does the color of our skin have any impact on our susceptibility to disease and how we experience it? As one scientist frames it:
The notion of “racial diseases”—that people of different races suffer from peculiar diseases and experience common diseases differently—is centuries old. It is tied to the original use of biology in inventing the political category of race.
Dorothy Roberts, Fatal Invention
Race and Disease
In the days of slavery, there were three racial groups that a human being could belong to; you were either white, slave or “other.” By the 2010 census, the number of races had grown to fifteen (1,2). While “white” as a race has always remained as a constant, other races such as blacks (negroes, slaves, coloreds, African Americans) have mutated over the years due to social and political factors(3).
According to information from the CDC, racial and ethnic minorities experience higher rates of sickness across a wide range of conditions such as hypertension, diabetes, asthma, obesity, and heart disease as compared to whites. A recent example is the COVID-19 pandemic, which had a disproportionate impact on racial and ethnic minorities highlighting the enduring health disparities. That said, the relationship between race and disease could be multifactorial. People in the same race or ethnicity are likely to share not only genetic characteristics inherited from common ancestors but also socio economic environments.
Currently, the federal government requires that all government funded research incorporates racial classifications in structuring and reporting results. The overall goal of doing this is to reduce race-based health disparities by determining how racial differences impact health and disease.
This raises two concerns; how is race defined and what is the utility and validity of racial differences in clinical research. One sociologist researcher named Catherine Lee analyzed NIH funded biomedical research that was published between 1990 and 1999. She arrived at the following conclusion:
Authors tended to see race or ethnicity as important and significant in their research. However, despite seeing the importance of race or ethnicity in their research, authors rarely defined or operationalized the concepts adequately. Moreover, when presenting findings of racial or ethnic difference, authors generally did not provide explanations of the difference. I argue that this under-theorized and unspecified use of race or ethnicity and the biological conclusions drawn about health and difference have the potential to reify “race” and to limit our thinking about what these biomedical differences suggest about health disparities and inequalities in general (4).
Biomarkers and Racial Disparities
Biomarkers have become important tools in assessing health status, susceptibility to disease, and response to treatment (5). However, biomarkers for chronic conditions are usually derived from clinical trials which in spite of an increased focus on racial inclusion still face a paucity of racial and ethnic representation. (6,7). This poses a few challenges; some of which we have highlighted below.
Racial disparities in biomarker testing for non-small cell lung cancer (NSCLC)
A retrospective observational study investigated the disparities in whites versus black patients with NSCLC who were undergoing biomarker testing and compared it with the rate of enrollment in clinical trials in the US (8). The researchers found a difference of over 10% in biomarker testing between the white and black populations. The researchers noted that this could have contributed to the more than double the rate of participation of whites compared to blacks in clinical trials. The researchers concluded that access to appropriate biomarker testing can help to ensure equal access to quality care.
A subsequent 2022 study revealed a similar trend where a statistically significant relationship was observed between biomarker/NGS testing and enrollment in clinical trials after adjusting for covariates (9).
Racial and ethnic disparities in participation in clinical trials: Oncology precision studies
A group of researchers carried out a cross-sectional research of cancer studies captured in the Clinicaltrials.gov registry targeting precision medicine objectives and that reported racial and ethnicity data. In total 93 studies with 5867 enrollees were included (10).
The study revealed that while minority racial groups were underrepresented, non-Hispanic whites were over-represented relative to the incidence of the partial cancers in those populations. The researchers concluded that there’s a need to increase racial diversity among enrollees in precision medicine trials so that all communities can benefit equally from cancer research breakthroughs and personalized treatments.
Why Are Asian Americans Underrepresented in Cancer Clinical Trials?
One study found that even though it is clear that Asian Americans are underrepresented in clinical trials, the cause remains unclear (11). This study ruled out cultural and religious barriers but emphasized the need for education on the benefits of participation in clinical trials.
A different study undertook to investigate the representation, awareness, and experience of Asian Americans in cancer clinical trials (12). The researchers handed out surveys to newly diagnosed cancer patients at outpatient oncology clinics. They made two observations:
Asians were less willing to participate in clinical trials and were less likely to know anyone who had participated in such
Asians were less likely to meet the inclusion criteria for most clinical trials
Failure to recruit minority populations in clinical trials impedes the generalizability of trial findings for these populations. It is therefore imperative to increase participation of the Asian community in biomarker and other clinical trials.
FDA Recommendations for Racial Diversity in Biomarker Studies
The FDA recommends that clinical trials represent the racial and ethnic diversity across different populations. To this end, the FDA formulated a draft guidance on April 14 last year that lays out the criteria for increasing enrollment of underrepresented groups in clinical trials. This draft mandates clinical trial sponsors to come up with a “Race and Ethnicity Diversity Plan” that should be provided to the FDA prior to the end of Phase 2 trials. The plan should highlight evidence, if any, that the safety and efficacy of a given drug, biologic, or medical device may vary due to racial factors. It should also include reports on the pharmacokinetic and pharmacodynamic investigations carried out by the trial sponsor. In addition, clinical trial sponsors must set enrollment goals that ensure equal representation of racial and ethnic minorities in clinical research.
The FDA outlines five distinct categories that researchers need to consider when creating a diversity plan for clinical trials. They are listed below:
Overview of the disease/ condition
Scope of medical product development program (scope of clinical trials)
Enrollment goals for underrepresented racial and ethnic participants
Specific plan for enrolling and retaining diverse participants
Status of meeting enrollment goals (as applicable)
While the FDA’s quest to mandate clinical trial sponsors to have a diverse cohort is noble, the practicality of it is wanting. As observed above, minorities are less likely to participate in clinical trials for various reasons. Even when they are willing, clinical researchers often face insurmountable challenges in their quest to obtain ethically sourced and racially diverse biosamples.
Garner Biosolutions has exclusive access to several hospitals across India that can provide biospecimens to help clinical trial sponsors meet racial and ethnic diversity goals. Our biospecimens are affordable, ethically sourced, traceable, and from a diverse population. In addition, you can make a bespoke biospecimen order to match the unique needs of your clinical trial. Contact us today and let us make your research a success!
References
Bhatnagar, M. (2007). Identifying the identified: The census, race, and the myth of self-classification. Tex. J. on CL & CR, 13, 85.
Hickman, C. B. (1996). The devil and the one drop rule: Racial categories, African Americans, and the US census. Mich. L. Rev., 95, 1161.
Racebox.org. The census since 1790. 2014 Retrieved 04/11/2014, from http://racebox.org/
Lee C. (2009). "Race" and "ethnicity" in biomedical research: how do scientists construct and explain differences in health?. Social science & medicine (1982), 68(6), 1183–1190.
Crimmins, E., Vasunilashorn, S., Kim, J. K., & Alley, D. (2008). Biomarkers related to aging in human populations. Advances in clinical chemistry, 46, 161–216.
Albert M. A. (2007). Inflammatory biomarkers, race/ethnicity and cardiovascular disease. Nutrition reviews, 65(12 Pt 2), S234–S238.
Sliwa, K., Stewart, S., & Gersh, B. J. (2011). Hypertension: a global perspective. Circulation, 123(24), 2892–2896.
Debora S. Bruno, Lisa M. Hess, et al (20210. Racial disparities in biomarker testing and clinical trial enrollment in non-small cell lung cancer (NSCLC). Journal of Clinical Oncology 2021 39:15_suppl, 9005-9005
Bruno, D. S., Hess, L. M., Li, X., Su, E. W., & Patel, M. (2022). Disparities in Biomarker Testing and Clinical Trial Enrollment Among Patients With Lung, Breast, or Colorectal Cancers in the United States. JCO precision oncology, 6, e2100427.
Aldrighetti CM, Niemierko A, Van Allen E, Willers H, Kamran SC. Racial and Ethnic Disparities Among Participants in Precision Oncology Clinical Studies. JAMA Netw Open. 2021;4(11):e2133205. doi:10.1001/jamanetworkopen.2021.33205
Ma, G. X., Seals, B., Tan, Y., Wang, S. Y., Lee, R., & Fang, C. Y. (2014). Increasing Asian American participation in clinical trials by addressing community concerns. Clinical trials (London, England), 11(3), 328–335.
Paterniti, D. A., Chen, M. S., Jr, Chiechi, C., Beckett, L. A., Horan, N., Turrell, C., Smith, L., Morain, C., Montell, L., Luis Gonzalez, J., Davis, S., & Lara, P. N., Jr (2005). Asian Americans and cancer clinical trials: a mixed-methods approach to understanding awareness and experience. Cancer, 104(12 Suppl), 3015–3024.
