Stronger Racial and Ethnic Minority Presence Is Needed in Clinical Cancer Trials | OncLive

Stronger Racial and Ethnic Minority Presence Is Needed in Clinical Cancer Trials

August 12, 2020

Numerous analyses conducted over the past few years have underscored a serious issue in clinical cancer trials that needs to be addressed: a lack of racial and ethnic diversity among participants.

Numerous analyses conducted over the past few years have underscored a serious issue in clinical cancer trials that needs to be addressed: a lack of racial and ethnic diversity among participants. Investigators who considered hundreds of trials across a wide range of tumor types and treatments not only found a significant lack of published racial data with regard to patients, but a dearth of ethnic participants all together.

Although there are several potential reasons for this, perhaps most prominent among them is the lack of patient trust because of historic and systemic mistreatment in clinical research settings. For example, in the US Public Health Service Syphilis Study at Tuskegee, investigators infected 600 black men with syphilis without their informed consent.1 Another example in the realm of infectious diseases was the Guatemala syphilis experiment, which tested the efficacy of penicillin (Pfizerpen) and the arsenic-based agent orvus-mapharsen in 5500 Guatemalan prisoners, sex workers, soldiers, children, and psychiatric patients, more than one-quarter of whom were purposefully infected with various sexually transmitted infections, and all of whom were enrolled without their consent.2

“Clinical trials are really where we improve the treatment of [patients with] cancer,” said Ruben Mesa, MD, director of the UT Health San Antonio MD Anderson Cancer Center. “Whether it be in terms of developing new therapies, new modalities, testing, radiation therapies, for those trials to really inform us, [they] need to really include the patient population [that we see in the clinic]—the actual people we are treating. In addition to issues around social justice and [racially and ethnically diverse] patients having access to those studies, study results are only really valid if they actually reflect the patients being treated [in practice].”

Several studies have examined why racial disparities exist within clinical cancer trials, the negative impact these disparities might have on the health of patients of color with cancer, and what healthcare professionals might be able to do to encourage more inclusivity in these trials.

Diversity in Prostate Cancer Clinical Trials

In one study, investigators analyzed 72 clinical prostate trials that were conducted from 1985 to 2019 that had a total of 893,378 pooled participants.3 Results showed that nearly all the patients enrolled on those studies were white men; this is especially problematic, as African American men have been found to have higher incidences of prostate cancer, as well as worse survival outcomes, according to the study authors. Latino men have also been shown to have a higher incidence of metastatic prostate cancer compared with white patients in the United States. Additional studies have indicated that the tumor biology of prostate cancer has been found to vary depending by race and ethnicity; however, research into these disparities and how they affect outcomes has been limited, according to the authors of the paper.

Results from the analysis showed that of the patients enrolled on prostate cancer screening trials specifically, 97.5% were white men, 0.5% were black or African American men, 0.4% were Asian men, 0.09% were American Indian or Alaska Native men, 0.2% were Hispanic or Latino men, and 1.3% were either another race or didn't have their race specified.

Results regarding representation proved to be similar with regard to prostate cancer treatment trials, as well, with 83.4% of participants being white, 6.7% being black or African American, 3.3% being Asian, 0.6% being American Indian or Alaska Native, and 0.9% being Hispanic or Latino. The same trend could be observed regarding participation on prostate cancer prevention trials, with 84.6% of participants being white, 8.5% black or African American, 0.2% Asian, 0.005% American Indian or Alaska Native, and 4.2% Hispanic or Latino.

Numerous factors that can lead to these racial disparities. In a separate interview with OncLive, Mesa touched on several potential contributors that might lead to underrepresentation on cancer clinical trials.

“Many contributors [can lead to a lack of diversity in clinical trials], including having the liberty and economic means to participate in those studies, having the concentration of those studies frequently occur at academic centers that have more limited geographic distribution, so more patients have to travel there, as well as corresponding expenses, employment barriers, and even awareness in health literacy,” said Mesa. “Because of that, we probably have less confidence that the outcomes that we see are applicable across all populations as we wish that they would be.”

Of the 844,002 participants who were enrolled on the studies and had racial and ethnic data available, 96% were white. A notable geographic disparity was also noted by investigators. Despite men of African descent having higher prostate cancer mortality rates, only 2 of 67 Caribbean and African countries were represented in these clinical trials.

Although some progress was made in terms of inclusion on these trials over the years—going from barely any racial or ethnic participation from 1985 to 1989 beyond white participants to only 69% of prostate cancer trial participants being white from 1995 to 1999—a notable decrease in the participation of African American participants can be observed from 1995 to 2014, dropping from 11.3% to just 2.8%.

To this end, investigators have proposed a benchmark goal of 56.3% non-Hispanic white participants and 22.2% non-Hispanic African American patients to be enrolled on prostate cancer clinical trials to solve for this problem. However, additional efforts must be dedicated to also incorporating other racial minorities, such as Hispanics and Latinos, for whom prostate cancer mortality is thought to have surpassed that of white patients, according to the investigators. Moreover, Asian patients are thought to have a significantly lower incidence of and mortality from the disease compared with other races, the study authors noted. As such, incorporating more of these patients on clinical trials could allow for further evaluation of protective factors against the disease, information that could have implications for prevention and treatment.

Moreover, negative beliefs surrounding trial participation and a lack of knowledge were indicated to be 2 of the biggest factors discouraging African American patients from enrolling on clinical trials in prostate cancer. To this end, improved patient navigation programs and stronger clinical trial infrastructure are needed to encourage minority participation.

Organizations such as the International Registry of Men with Advanced Prostate Cancer (IRONMAN) are testing similar methods to help encourage more diverse patient populations to enroll on clinical prostate cancer trials; this includes the IRONMAN Diversity Working Group and Advocacy Working Group and building clinical trial infrastructure in countries that have previously been excluded from clinical trials, such as Brazil and South Africa.

Challenges With Pediatric Clinical Trial Participation

Another analysis, which was part of a larger study, was aimed at examining factors associated with parents and guardians declining to have their child participate in a pediatric oncology next-generation sequencing (NGS) study. The most significant demographic variable that was associated with decline to participate in the clinical trial was race and ethnicity, with the families of black children being far more likely to refuse participation, according to the study authors.4

“For any research, ethnic and racial diversity are important in order for the findings to be representative of the general population, including racial and ethnic minorities,” said Katianne M. Howard Sharp, PhD, lead author of the study and an instructor within the Department of Psychology at St. Jude Children's Hospital. “Historically, minorities undergoing genetic testing have been more likely to receive results of a variant of uncertain significance in cancer predisposition genes, which refers to a germline variant that is unclear and in need of further research.”

Next-generation sequencing has the potential to benefit pediatric cancer care, as it has already helped to estimate that 5% to 15% of children with cancer have some manner of underlying predisposition, such as adult-onset cancers. However, it is believed that in order to make genomic sequencing equally available to all patients in clinical practice, it’s important to be inclusive of racially and ethnically diverse patients in clinical trials, according to the study authors.

In the trial, investigators examined factors that lead to parents refusing study participation in Genomes for Kids (G4K; NCT02530658), an initiative that offered comprehensive genomic tumor analysis, as well as analysis of germline tissues, to pediatric patients with cancer.

From August 2015 to April 2017, investigators collected data on 363 children who were approached for enrollment on G4K at St. Jude's Children's Research Hospital. Pediatric patients enrolled on the study would receive germline sequencing and results for 63 cancer predisposition genes would be provided to the families. The families of patients on the study were re-contacted with updated results based on new findings; an additional 93 genes were added over the course of the study, which resulted in a total of 156 different cancer predisposition genes. Participants had to be 21 years of age or younger and needed a diagnosis of a liquid or solid non–central nervous system (CNS) tumor or a solid CNS tumor.

From there, investigators examined different patient demographic and clinical criteria, including sex, race, ethnicity, region of residence within the United States, as well as parental factors, such as age at diagnosis, education level, marital status, sibling status, and religion. Of the families who were approached to participate in the trial, 14.6% (n = 53) declined to have their child enrolled. Investigators found that the families of black children were notably more likely to refuse enrollment compared with families of non-Hispanic white children (odds ratio [OR] = 4.50; 95% CI, 2.29-8.84; P <.001). Other factors, such as a father's marital status (OR = 3.75; 95% CI, 1.69-8.30; P <.001) or a need for an interpreter (OR = 0.16; 95% CI, 0.02-1.21]; P = .076) were not found to have a significant impact on declining trial participation.

“Black children [and their families] were more likely to decline enrollment, even when controlling for other demographic and clinical factors that might be related to enrollment in genetic research,” Howard Sharp explained. “For example, income and access to care have been described as variables potentially related to genetic testing access and access to genetic testing research.”

However, as patients accepted by St. Jude will receive treatment regardless of whether or not their families have insurance or can pay for it, this potentially excludes income as a factor of refusal to enroll, according to Howard Sharp.

Among the families who did not want their children to participate, 87.5% were willing to provide a reason why. Accessibility, paired with a parent refusal rate ranging from 12% to 30% over concerns of discrimination (insurance discrimination and privacy violations) and psychological impact of mutation disclosure, has led to a dearth of diverse patient populations on these trials. The most common reason provided for declining was because they were feeling overwhelmed (22.9%), while others opted for targeted clinical genetic testing (20%). Others reasons included concerns over insurance discrimination (17.1%), the child themselves did not wish to participate (17.1%), some did not want to know the results (11.4%), and some didn't see a direct benefit for their child (8.6%). These rates of refusal indicate a need for further consideration of diversity and inclusion when it comes to recruiting efforts for these trials.

“One of our goals is to increase representation of minorities in genetic research by fostering trust both in that medical research and in the institution,” concluded Howard Sharp. “We [hope] to increase this through practices such as increased transparency in how genetics information will and will not be used, as well as how privacy will be ensured. That way, patients can know what they are and are not consenting to.”

References

  1. US Public Health Service Syphilis Study at Tuskegee. Centers for Disease Control and Prevention. Centers for Disease Control. Updated March 2, 2020. Acces sed July 22, 2020. https://bit.ly/2XFv8cY.
  2. Rogers K. Guatemala syphilis experiment. Encyclopaedia Britannica. March 18, 2018. Accessed July 22, 2020. https://bit.ly/3fDj9CR.
  3. Rencsok EM, Bazzi LA, McKay RR, et al. Diversity of enrollment in prostate cancer clinical trials: current status and future directions. Cancer Epidemiol Biomarkers Prev. 2020;29(7):1374-1380. doi: 10.1158/1055-9965.EPI-19-1616
  4. Howard Sharp KM, Jurbergs N, Ouma A, et al. Factors associated with declining to participate in a pediatric oncology next-generation sequencing study. JCO Precis Oncol. 2020;4:202-211. doi:10.1200/PO.19.00213

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