Global regulatory agencies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) utilize the answers provided by clinical trials to evaluate the safety and efficacy of novel therapies, inform medical professionals on the use of new therapeutic agents and make approval decisions³.The importance of clinical trials to provide evidence regarding pharmacokinetics/pharmacodynamics, safety, and efficacy of potential treatments across different demographic populations can’t be overstated³.

When clinical trials fail to include racial and ethnic diversity into medical research, it can be harmful for large segments of the population – especially if these trials involve the research of new drugs or combinations of drugs, new ways of doing surgeries or improvements to existing treatments. Clinical trials that only focus on a subset of the population can lead to medical advancements that only work for some people by ignoring the diverse genetic, environmental, cultural and lifestyle factors that play a key role in the development and treatment of medical conditions.

Depending on the topic of the study, different populations of people may be recruited as test subjects. Some studies may only require healthy volunteers, some may look at diseases primarily occurring in just men or just women, while others may have an age restriction¹. But even with such variations in study populations, diversity and racial representation in clinical trials is particularly important. Historically, there has always been a vast imbalance in racial representation in clinical trials and certain racial and ethnic groups of people have not been well represented².  

To combat this, the U.S. Congress passed the National Institutes of Health Revitalization Act in 1993 as a means to improve the enrollment of minorities in clinical trials⁶. This policy was subsequently updated in the year 2000 to require the inclusion of women and minority groups in all “biomedical and behavioral research projects involving human subjects” unless there was a clear justification for their exclusion¹². Other national and international efforts to increase and facilitate greater diversity in clinical trials included the Federal Drug Administration Race and Ethnicity Guidance, as well as the International Conference on Harmonization Guidance⁴. Yet, even with such measures and calls for the inclusion of racial/ethnic minorities and women in late-phase clinical research studies, these minority groups remain vastly underrepresented.

In fact, 92% of participants in clinical trials conducted back in 1997 were Caucasian and in 2014, this figure was still at a resounding 86%⁷.

Same, Same, but Different?

People may experience the same disease and its treatment very, very differently. Including people from a variety of backgrounds and living conditions, as well as acknowledging features like race and ethnicity means that all communities could potentially benefit from scientific advances. It has long been known that population differences in disease prevalence, pathophysiology, and outcome can often be attributed to a variety of factors, such as genetic differences in cases of cystic fibrosis, sickle cell disease, or breast cancer suppressor gene abnormalities for instance⁷. Differences in biomarkers, such as estrogen receptor positivity or negativity in breast cancer, environmental differences, lifestyle choices, like tobacco use or a sedentary routine, and social factors can all differ amongst different races and ethnicities⁷.

Most recently, COVID-19 vaccine trials fundamentally highlighted these disparities. While African American individuals represented 21%of COVID-19 deaths in the United States, they made up only 3% of major vaccine trial participants⁶.

Racial and ethnic gaps in data collection can significantly skew medical evidence and its associated innovation towards therapies that lack appropriate efficacy and safety measures for minority populations⁶. Clear mismatches between the populations being studied and those on which therapy will be focused on, exist more often than we know.

One particularly eye-opening example of the consequences that result when representative populations are omitted from clinical trials are the recommendations that were made after a large-scale trial examined the effect of the drug tamoxifen on breast cancer prevention⁸. ‍

13,388 women were studied over a span of 5 years – of which only 220 were African American (a group with a slightly lower breast cancer incidence, but a higher mortality) and 249 women were other unspecified minorities⁸.

Even though the number of included minorities was extraordinarily low, the published guidelines suggested that African American women should be counseled against preventative therapy with tamoxifen when 10 years younger than non-AfricanAmerican women⁹. Such recommendations can clearly be potentially dangerous to a whole subset of the population, and in fact, subsequent studies showed that tamoxifen therapy was equally as effective in African American women after all¹⁰.

‍So What About Cancer?

There are more than 100 types of cancer affecting every type of cell known to man. Unsurprisingly, oncology makes up the majority of clinical trial research worldwide.

At LARVOL, following oncology clinical trials is our bread and butter! We strive to make clinical trial data as accessible and simple to follow as possible. For more information, request a demo here!

Cancer can affect each and every one of us. It affects people of all races, ethnicities, genders, and ages. It is important to consider health disparities, including health outcomes influenced by unequal access to health insurance or differences in the incidence and survival rates for people with cancer that exist among racial or ethnic minority groups³.

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Certain minority groups report a higher incidence of certain cancers.

For instance, multiple myeloma, colorectal cancer, triple negative breast cancer or prostate cancer all occur disproportionately more often in African American individuals³. While others, such as gastric cancers are more prevalent among Asians and Pacific Islanders³.According to the CDC, African American men have more lung, prostate, colon, and rectal cancers than Caucasian men and, overall, AfricanAmerican men have more malignant tumors and are less likely to survive cancer than the general population¹¹.‍

There is a real-world need for clinical oncology trials to adequately represent diverse racial and ethnic groups to better reflect the populations that are most likely to benefit from a drug.

Particularly, considering that for clinical oncology trials conducted in the United States, the distribution was still heavily skewed towards Caucasians (84%) – with minimal representation of African Americans(7.3%), Asians (3.4%) and Hispanics/Latinos (2.8%) based on literature published in 2019³.

To promote social justice and health equity and ultimately produce more innovative science, including a diverse range of people from different communities in clinical oncology trials is of vital importance and much work still remains to be done moving forward.‍

How Can We Do Better as Clinicians and Researchers?

Diversity in clinical oncology trials matters because it promotes equitable access to effective cancer treatments, helps identify differences in treatment responses among diverse patient populations, and can help reduce health disparities.
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Some strategies that may encourage increased participation of minorities in clinical trials include:

1. Engaging with communities:
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   Historically, lack of information due to the types of institutions where patients receive care and general patient mistrust has proven to be a major factor in limited involvement of minorities in clinical trials³.
   
   Collaborating with community organizations and leaders could help raise awareness of clinical trials, while also being an opportunity to appropriately address any concerns or mistrust that may exist in those communities. This can involve the use of targeted outreach efforts and culturally appropriate educational materials.
   
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2. Addressing barriers to participation:
   
   Sociodemographic and health-related factors often prevent many patients from receiving definite therapy. In a study comparing the receipt of non-definitive therapy and survival among patients with high-risk prostate cancer, African American and Hispanic patients were more likely to only receive systemic therapy or not be treated at all compared to their Caucasian counterparts³.
   
   Systemic barriers such as lack of access to transportation, language barriers, and financial constraints can prevent individuals from participating in clinical trials.
   
   Addressing these barriers can involve providing transportation or childcare, offering interpreter services, and providing financial compensation for participation.
   
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3. Increase diversity in clinical trial staff:
   
   Previous studies have shown that African American patients were more comfortable being approached by and engaging with an African American recruiter⁶.Additionally, in predominantly Caucasian medical settings, African American patients were also more likely to comply with prescribed procedures when recommended by an African American physician⁶.
   
   More clinicians and researchers from underrepresented groups are needed to help build trust and confidence in clinical trial participation. Having a diverse staff can help create a more welcoming and inclusive environment for participants.
   
   This can involve actively recruiting and hiring staff from diverse backgrounds and providing diversity and cultural competency training.
   
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4. Using diverse recruitment methods:
   
   Traditional recruitment methods such as advertisements in medical clinics and hospitals may not reach all populations.
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   Broader audiences may be reached by using alternative recruitment methods, such as social media, community events, and word-of-mouth referrals.
   
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5. Considering cultural factors:
   
   Cultural factors can affect how individuals view clinical trials and participate in them. On average, physicians were found to spend less time with African American than Caucasian patients and not recommending participation in their trials as often³.
   
   Understanding and addressing cultural factors can involve adapting study protocols and materials to be culturally appropriate and providing cultural sensitivity training to clinical trial staff.
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Overall, increasing diversity in clinical trials is a multifaceted process that requires a combination of steps, so we as healthcare providers can move towards ensuring equitable access to effective treatments for all populations.

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Representation in clinical trials matters.

Both on the side of the research scientists trying to connect with people from different cultures, as well as their participants.

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References:

1. NIH: National Institutes of Health[Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2022 Oct3]. NIH Clinical Research Trials and You; [updated 2022 Oct 3]. Available from:https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics.
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2. NIMHD: National Institute on MinorityHealth and Health Disparities [Internet]. U.S. Department of Health & HumanServices, National Institutes of Health [updated 2023 Mar 15]. Diversity andInclusion in Clinical Trials; [updated 2023 Mar 15]. Available from: https://www.nimhd.nih.gov/resources/understanding-health-disparities/diversity-and-inclusion-in-clinical-trials.html.
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3. Camidge DR, Park H, Smoyer KE, Jacobs I, Lee LJ, Askerova Z, McGinnis J, Zakharia Y. Raceand ethnicity representation in clinical trials: Findings from a literature review of Phase I oncology trials. FutureOncology,202117:24,3271-3280
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4. TurnerBE, Steinberg JR, Weeks BT, Rodriguez F, Cullen MR. Race/ethnicity reporting and representation in US clinical trials: A cohort study. The LancetRegional Health - Americas, Volume 11, 2022, 100252, ISSN 2667-193X. https://doi.org/10.1016/j.lana.2022.100252.
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5. Taylor AL, Wright JT. Should ethnicity serve as the basis for clinical trial design? Importance of Race/Ethnicity inClinical Trials. Lessons From the African-American Heart Failure Trial(A-HeFT), the African-American Study of Kidney Disease and Hypertension (AASK),and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart AttackTrial (ALLHAT). Circulation, 2005;112:3654–3666. https://doi.org/10.1161/CIRCULATIONAHA.105.540443
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6. Segre LS, Chuffo Davila R, Carter C,Arndt S. Race/ethnicity matching boosts enrollment of black participants in clinical trials. Contemporary Clinical Trials, 122 (2022) 106936.
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7. Knepper, TC, McLeod, HL. When will clinical trials finally reflect diversity? Nature 557,157-159 (2018). doi: https://doi.org/10.1038/d41586-018-05049-5
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8. Fisher B, Constantino JP, WickerhamDL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, AtkinsJ, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolnark N. Tamoxifen for prevention ofbreast cancer: report of the National Surgical Adjuvant Breast and BowelProject P-1 Study. J Natl Cancer Inst. 1998;90:1371–1388.
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9. Gail MH, Costantino JP, Bryant J, Croyle R, Freedman L, HelzlsouerK, Vogel V. Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J Natl Cancer Inst. 1999;91:1829 –1846.
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10. McCaskill-Stevens W, Wilson J, BryantJ, Mamounas E, Garvey L, James J, Cronin W, Wickerham DL. Contralateral breast cancer and thromboembolic events in African-American women treated with tamoxifen. J Natl Cancer Inst. 2004;96:1762–1769.
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11. Disparities in cancer care. J Oncol Pract. 2006 Sep;2(5):234-9. doi:10.1200/JOP.2006.2.5.234. PMID: 20859342; PMCID: PMC2793626.
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12. Flores,LE, Frontera, WR, Andrasik, MP, Del Rio, C, Mondriguez-Gonzalez, A, Price, S,Krantz, EM, Pergam, SA, Silver, JK. Assessment of the inclusion of racial/ethnic minority, female, and older individuals in vaccine clinical trials. JAMA Network Open. 2021;4(2):e2037640.doi:10.1001/jamanetworkopen.2020.37640