Learn how research can neglect certain groups of people and unintentionally have negative impacts on them.
Health research helps advance disease knowledge, treatment, and quality of life for people living with chronic diseases like arthritis. However, if care is not taken, research can neglect certain groups of people and unintentionally have negative impacts on them. One of the key reasons this happens is related to “representation”. Representation refers to who is and who is not included in research as study subjects in trials are supposed to reflect the population that’s affected. For example, are study participants of different genders and ages or of diverse racial backgrounds?
These questions are important because when research is conducted with primarily one group of people (e.g. white adults), benefits are both limited and skewed. It discounts the input, experiences and medical data of a much more diverse real-world patient population. Results cannot be generalized to all patients and may even end up worsening health inequities that already exist.
For example, in the multi-billion dollar race to develop a vaccine for COVID-19, representation has become an obstacle because researchers haven’t recruited sufficient numbers of minorities to join the clinical trials. Of the 350,000 people in the United States who’ve registered online for a coronavirus clinical trial, 10% are Black or Latino. That’s not nearly enough as research shows that more than half of United States coronavirus cases have been among Black and Latino people.
For a brief overview of health inequities and what causes them, read the first article in our Health Inequities series.
Underrepresentation in clinical trials
Thanks to the hard work of many patient advocates, research has become more diverse, inclusive and patient-centred in recent decades. However, change is still needed in many areas particularly when it comes to clinical trials. A clinical trial is a type of research study involving patient volunteers aimed at answering specific treatment questions. In arthritis for example, clinical trials may be conducted to find out whether a new medication is safe and effective or how a new medication compares to existing ones. When certain groups of people are excluded from these trials, little is known about how treatments will impact them.
Women continue to be underrepresented in clinical trials, particularly elderly women and women who are pregnant. In fact, pregnant women are routinely excluded from drug studies4. As a result, women have had to make very difficult decisions about whether or not they will continue medication while pregnant with little information about how a drug will impact them or their fetus. Dr. Mary De Vera and her team at Arthritis Research Canada are addressing this gap by conducting research that is specifically focused on pregnancy and use of arthritis medications. Watch this video to learn more.
It is important to note that Health Canada recommends for women to be included in clinical trials and the federal government has also made a commitment to ensuring sex and gender is routinely considered when analysing research. However, a 2019 study has shown that underrepresentation in a number of disease areas still persists in Canada1. The researchers believe that this is due to policies not being well implemented or the fact that they are primarily just recommendations which are not always followed. Overall, gender representation is deeply important because women’s smaller body sizes, higher fat contents and hormone levels mean that their drug responses can differ greatly from men’s.
People from racial minority groups are also underrepresented in clinical trials. This is true across a number of different disease areas including those which disproportionally impact communities of colour, such as arthritis and cancer2,3,4. A study found that overrepresentation of white participants and underrepresentation of minorities exist in clinical trials for rheumatoid arthritis (RA) treatments. The study found that between 2008-2018, white participants made up 74.6% to 97% of study participants in RA trials4. In another study, researchers found that fewer than 8% of trials for approved cancer drugs in the United States reported participants from all four of the country’s major racial groups (White, Asian, Black and Hispanic)3. Only 22% reported Black participants, even though the population has a high incidence of certain cancers. Their results also showed that racial reporting and representation has only minimally increased in the last decade.
While both of these studies were conducted in the US, their findings are also relevant to Canada. Dr. Jonathan Loree, assistant professor in the division of medical oncology at the University of British Columbia says that pharmaceutical companies often apply for drug approval through the FDA first (the drug approval body in the US) because it serves the largest market. Then they submit to Health Canada and the clinical trials considered in the approvals are commonly the same as those used in the US5.
Lastly, clinical trials often have strict criteria that prohibit elderly folks and people with multiple health conditions from participating4. This issue is particularly important in arthritis research as many patients are elderly and/or have multiple chronic conditions. Thus, the exclusion of these groups mean that clinical trials are not reflecting a ‘real-world’ setting with typical arthritis patients. In a recent #CRArthritis interview, Dr. Sasha Bernatasky explained how she and Dr. Glen Hazlewood are working to tackle this issue through pragmatic trials. Pragmatic trials are a type of clinical trial that more closely resemble the real world. For example, they have less strict inclusion criteria so that seniors and people with multiple health conditions can participate. Dr. Bernatasky and Dr. Hazlewood are working to set up a network within Canada that could support more pragmatic trials in rheumatology.
Overlapping demographic factors affecting representation in research: As described above, racial minorities, women and seniors are particularly underrepresented in clinical trials. It is important to consider what this means for patients who are in more than one of these groups. How much research do you think represents an elderly black woman with multiple chronic conditions? How does this compare to representation of an elderly white woman, or, a young white man? These questions refer to something called intersectionality. Intersectionality considers the overlapping factors of age, race, gender, income and disability that make up a person’s identity and experiencs11. Intersectionality helps us to understand the different layers of discrimination or privilege that a person may experience. Researchers are increasingly taking an intersectional perspective in their studies to ensure the complex experiences of different patients are included.
Personalized and precision medicine – who is it leaving behind?
“Personalized and precision medicine” may be the future of inflammatory arthritis treatment. In fact, it was the theme of the 2018 Canadian Rheumatology Association (CRA) and Arthritis Health Professions Association (AHPA) Annual Scientific Meeting. According to the Canadian Institutes of Health Research, personalized and precision medicine refers to “the identification of biomarkers and genetic signatures for prevention and prediction of therapeutic response”6. In other words, instead of taking a trial and error approach to finding the right medication(s), precision medicine would use a patient’s genetic information to help identify the right treatment for them in a timely manner. Precision medicine represents an exciting shift from “one size fits all” healthcare to a more personalized system. However, racial minorities have been found to be underrepresented in the case of genetic research for precision medicine. A 2018 analysis found that more than 80% of genome-wide association studies in the United States were based on people of European descent7. People of African and Latin American ancestry, Hispanic people and Indigenous peoples are particularly underrepresented in these studies. Together, they make up less than 4% of all samples analyzed7. This represents a huge gap in genomics research and precision medicine for minority communities8.
Taking steps forward
How can we ensure that all patients are included in the future of arthritis treatment and clinical trials? Some evidence-based recommendations are listed below.
- Building trust and research partnerships – One of the reasons that racial minorities are often underrepresented in research is due to a long history of mistrust between minority communities and healthcare providers/researchers9. For trust to be re-built, genuine research partnerships must be established. This means including patients in some or all stages of the research process from deciding what topic is studied, to how the research is conducted to how the findings are presented and used. Patient partners should be of diverse genders, ages and races to ensure different patient voices are included in the research process. To learn more about patient partnerships in research, check out this Arthritis Broadcast Network article.
- Fostering diversity among researchers and healthcare teams – Representation is about who participates and who conducts a study. Evidence shows that people are more likely to participate in a clinical trial when they feel a level of familiarity with the researcher or physician who approaches them about the study10. A diverse team of clinician researchers not only helps participants to feel more comfortable but also ensures that studies are not developed and conducted from an only white or male perspective.
- Addressing language barriers – Ensuring systems are in place to facilitate the participation of people who do not speak English will also improve people’s ability to participate in clinical studies. To learn more about overcoming language barriers in healthcare, check out our article on The Language Gap.
Go deeper: Other articles in this series
- Understanding Health Inequities in Canada: What shapes a person’s health?
- Spotlight on Indigenous Peoples and Barriers to Arthritis Care
- The Language Gap
Learn more about equity in research:
In this Arthritis At Home interview, learn how clinician researcher Nevena Rebić incorporates social justice, anti-racism and decolonization practices into her work.
- Yakerson, A. Women in clinical trials: a review of policy development and health equity in the Canadian context. International Journey for Equity in Health; 18(56). (2019) https://equityhealthj.biomedcentral.com/track/pdf/10.1186%2Fs12939-019-0954-x
- O’Reilly ED, Snyder A. The cost of racial disparities in clinical trials. Axios. (June 18 2020). https://www.axios.com/black-americans-diseases-clinical-trials-2acaa476-0ec8-4362-8e90-2f5c3c85c916.html
- Loree JM, Anand S, Dasari A, et al. Disparity of race reporting and representation in clinical trials leading to cancer drug approvals from 2008 to 2018. JAMA Oncology;5(10). e191870–e191870 (2019). doi:10.1001/jamaoncol.2019.1870
- Strait A, Castillo F, Choden S, et al. Demographic Characteristics of Participants in Rheumatoid Arthritis Randomized Clinical Trials: A Systematic Review. JAMA Netw Open.2(11) :e1914745 (2019) doi:10.1001/jamanetworkopen.2019.14745
- University of British Columbia. Study finds lack of racial diversity in cancer drug clinical trials. Medical Express. (2019). https://medicalxpress.com/news/2019-08-lack-racial-diversity-cancer-drug.html
- CIHR. Personalized medicine overview. Government of Canada. https://cihr-irsc.gc.ca/e/43707.html
- Popejoy A, Fullerton S. Genomics is failing on diversity. Nature. (October 12 2016). https://www.nature.com/news/genomics-is-failing-on-diversity-1.20759
- Perera, M. Leaving some behind: the growing gap in precision medicine for minority populations. Expert Review of Precision Medicine and Drug Development, 4:1, 3-5. (2019). https://www.tandfonline.com/doi/full/10.1080/23808993.2019.1529541
- Occa, A., Morgan, S.E. & Potter, J.E. Underrepresentation of Hispanics and Other Minorities in Clinical Trials: Recruiters’ Perspectives. Journal of Racial and Ethnic Health Disparities 5, 322–332 (2018). https://doi-org.ezproxy.library.ubc.ca/10.1007/s40615-017-0373-x
- Koehn, C. The role of ethnicity in willingness to participate in arthritis clinical trials. The journal of Rheumatology. 23(12) 2283-2284. (2005)
- Kimberlé Crenshaw: What is intersectionality? YouTube. (June 22, 2018). https://www.youtube.com/watch?v=ViDtnfQ9FHc