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The Demographic-Related Biases of Clinical Trials

Authored by Nambita Sahai

Art by Michelle Choi


Undoubtedly, research trials have played an indispensable role in promoting global health. They have been instrumental in developing the newest treatments and drugs to manage a plethora of diseases. However, are they all equitable? A simple change in demographics can potentially skew the results of a study. For example, geographic location can affect lifestyle differences like nutrition, environmental risk, etc. This is evident in countries like Korea, Japan, and China which experience higher rates of stomach cancer due to H. Pylori and differences in cuisine [1]. This should prompt us to account for human diversity in research by geographic demographics, gender, and more. 


Additionally, up to 80% of behavioral and social studies overrepresent the Western, Educated, Industrialized, Rich, and Democratic (W.E.I.R.D) population [2]. Despite Congress passing the National Institutes of Health Revitalization Act to increase minority and female participation in studies, there is still a large lack of representation, even when minority subpopulations are more likely to have that disease [3]. Essentially, the results of this research only cater to a subset of rich participants from a certain locality — such as college students in the United States — failing to account for proper diversity in trials [2]


It would be remiss to ignore the importance of maintaining diversity in animal model research as well. It has been shown that male mice are systematically used at greater rates than female mice. Typically, this is done under the assumption of higher variability in experiments with females due to greater hormone changes [4]. Even in vitro studies, or those done out of living organisms, fail to specify if cells have come from male or female lines, which could create an imbalance in the process [5]. This makes it challenging to generalize a single study to an entire population and results in an inability to recognize the variability in patient outcomes [6]. 


Even after the research is finished, there can be considerable bias in what is published. For example, a study shows that mentioning the sample country in a title affects paper evaluations ​​[7]. Countries that are low-income tend to be less represented in medical journals, and “diseases of poverty” are less likely to be featured [8]. There is also systematic underfunding for diseases that affect women, such as endometriosis, versus those that primarily affect men [9]


So, if diversity is so important, what can we do to make our trials more representative? Some proposed methods include: 


  1. Increasing the Diversity of Researchers


A diverse set of researchers has been shown to generate new research questions and new perspectives [10]. Ensuring that the people conducting the research are diverse makes it easier to ensure that the variety of opinions and problems focus on the research itself [11]. 


  1. Spreading the Importance of Volunteering in Trials


As participating in clinical trials is voluntary, it is important to spread the importance of having diverse participants in trials. Acknowledging historical events — like the Tuskegee experiment causing medical mistrust among populations such as minority communities — is one approach to making volunteering more accessible [12].  The Tuskegee experiment involved unethical testing on African American men, causing preventable illness [12]. Ultimately, history must be addressed to make trials more accessible. 


  1. Broadening Inclusion Criteria and Removing Unjustified Exclusion


It is important to attempt to include as many populations as possible, such as those who are older or those with abnormal weights, if there is no scientific justification as to why they should not be part of the study [13]


  1. Introducing Flexibility in Research Sites (Location, Accessibility to Visit)


For example, the FDA suggests having clinical research sites in locations with large minority populations, using social media recruitment with multiple languages, and strengthening engagement with communities through organization and outreach in order to increase diversity and participation in clinical trials [14]. Scientists should aim to reduce as many barriers as possible during the design of their experiments. 


These are only some approaches to make sure that we continue to publish and fund diverse and equitable research that will help as many people as possible around the world.


References

  1. Azar, B. (2010, May 1). Are your findings 'WEIRD'? American Psychological Association. Retrieved April 16, 2023, from https://www.apa.org/monitor/2010/05/weird

  2. Clinical Trials Have Far Too Little Racial and Ethnic Diversity. (2018, September 1). Scientific American. https://www.scientificamerican.com/article/clinical-trials-have-far-too-little-racial-and-ethnic-diversity/

  3. Rozenbaum, M. (2019, August 3). Why we need female mice in drug trials. Understanding Animal Research. Retrieved April 16, 2023, from https://www.understandinganimalresearch.org.uk/news/why-we-need-female-mice-in-drug-trials#:~:text=In%20fact%2C%20in%20scientific%20studies,reported%20only%2024%25%20were%20female

  4. Karp, N. A., & Reavey, N. (2018). Sex bias in preclinical research and an exploration of how to change the status quo. British Journal of Pharmacology, 176(21), 4107–4118. https://doi.org/10.1111/bph.14539

  5. Duscheck, J. (2017, march 20). Studies of scientific bias targeting the right problems. Stanford Medicine News Center. Retrieved April 16, 2023, from https://med.stanford.edu/news/all-news/2017/03/studies-of-scientific-bias-targeting-the-right-problems.html

  6. Kahalon, R., Klein, V., Ksenofontov, I., Ullrich, J., & Wright, S. C. (2021). Mentioning the sample's country in the article's title leads to bias in research evaluation. Social Psychological and Personality Science, 13(2), 352-361. https://doi.org/10.1177/19485506211024036

  7. Yousefi-nooraie, R., Shakiba, B., & Mortaz-hejri, S. (2006). Country development and manuscript selection bias: A review of published studies. BMC Medical Research Methodology, 6(1). https://doi.org/10.1186%2F1471-2288-6-37

  8. Mirin, A. A. (2021). Gender disparity in the funding of diseases by the U.S. national institutes of Health. Journal of Women's Health, 30(7), 956–963. https://doi.org/10.1089/jwh.2020.8682

  9. Swartz, T. H., Palermo, A.-G. S., Masur, S. K., & Aberg, J. A. (2019). The science and value of diversity: Closing the gaps in our understanding of inclusion and diversity. The Journal of Infectious Diseases, 220(Supplement_2), S33-S41. https://doi.org/10.1093/infdis/jiz174

  10. Kozlowski, D., Larivière, V., Sugimoto, C. R., & Monroe-white, T. (2022). Intersectional inequalities in science. Proceedings of the National Academy of Sciences, 119(2). https://doi.org/10.1073/pnas.2113067119

  11. Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry. (n.d.). FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enhancing-diversity-clinical-trial-populations-eligibility-criteria-enrollment-practices-and-trial

  12. Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry. (n.d.). FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enhancing-diversity-clinical-trial-populations-eligibility-criteria-enrollment-practices-and-trial

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