Real-World Evidence: Research Reveals a Lack of Racial Diversity in Clinical Trials for Cancer Drugs

Clinical trials for cancer drugs lack racial and ethnic diversity in their populations, according to findings published in August in JAMA Oncology.¹

Researchers from the University of British Columbia (UBC), The University of Texas MD Anderson Cancer Center, the Fred Hutchinson Cancer Center, and Baylor University sought to evaluate the frequency of race reporting and representation in 230 trials supporting FDA oncology drug approvals from July 2008 to June 2018. The study authors analyzed 112,293 participants from the 4 major racial and ethnic groups in the United States: white, black, Asian, and Hispanic. Taking into account that some trials reported on more than 1 group, these are the results:

• 144 (62.6%) trials reported on the white population

• 110 (47.8%) trials reported on the Asian population

• 88 (38.2%) trials reported on the black population

• 23 (10%) trials reported on the Hispanic population

Among the 230 trials, 145 (63%) reported on at least 1 group, 18 (7.8%) reported on the 4 major groups, and 58 (25.2%) reported on racial and ethnic subgroups. The differentiation of race reporting in trials between July 2008 and June 2013 versus July 2013 and June 2018 changed nominally (45 trials [56.6%] vs 100 trials [67.1%]; odds ratio [OR], 1.63; 95% CI, 0.93-2.87; P = .09), as did race subgroup analysis (13 trials [16.1%] vs 45 trials [30.2%]; OR, 2.26; 95% CI, 1.16-4.67; P = .03).

The data also revealed a stark contrast in representation for the black and Hispanic populations, at 3.1% and 6.1%, respectively.

Black and Hispanic participants also were underrepresented in trials in regard to rates of cancer incidence, at 22% and 44% of their expected rate of cancer; by contrast, whites were enrolled at 98% and Asians at 438% of their expected rate of cancer incidence. The lack of representation by black and Hispanic enrollees was further exemplified by the minimal change in proportion from each race enrolled between July 2008 and June 2013 versus July 2013 and June 2018 (blacks, 3.6% vs 2.9%; Hispanics, 5.3% vs 6.7%).

A lack of diversity in cancer studies was previously documented. Scientists from Johns Hopkins’ Bloomberg School of Public Health wrote in 2018 how fewer than 5% of breast cancer studies were stratified by race and socioeconomic factors.² These researchers emphasized the need to prioritize social factors like race to understand correlating vulnerability and mortality rates with specific ethnicities.

For many years, assessment devices like the Breast Cancer Risk Assessment Tool were only validated for white women, which significantly underestimated the risk of breast cancer in black women, who have higher rates of breast cancer at younger ages.² By utilizing data from a primarily white study group, scientists ignore the impact of cancer drug efficacy on the other 3 major race groups, which may prove detrimental to survival rates.

Lead study author Jonathan Loree, MD, assistant professor in the Department of Medicine, Division of Medical Oncology at UBC,1 provided an instance in which a medication used to treat lung cancer showed mediocre trial results in the general population but exhibited incredible responses among nonsmoking young women in a study in Asia due to a genetic mutation common in this population.3 Asked in an interview how physicians reacted to his findings, Loree expressed his own astonishment.

“I think physicians were aware that disparities might exist based on prior work; however, the magnitude of disparity noted in our study is something that is quite surprising,” he said. Delving into the distinctions found in each race can unveil personalized approaches to treating patients based on social factors, but the disparity in race enrollment inhibits this interpretation.

Senior investigator in the study Kanwal Raghav, MBBS, MD, assistant professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer, provided additional insight on how to combat these disparities. “A potential step in this direction would be if the regulatory agencies request post approval studies fueled with real-world data to help generate evidence and fill the disparity gaps for otherwise underrepresented subgroups in initial studies,” Raghav said in an email.

Raghav’s idea for real-world data involvement is an approach the FDA called for in a framework released in December 2018.⁴ Back in 2016, Congress passed the 21st Century Cures Act, which directed the FDA to develop processes for using real-world evidence (RWE) in the course of drug regulation.⁵ The FDA joined COTA Healthcare in a 2-year research and collaboration agreement to reform treatment through RWE and electronic health records (EHRs). Starting with breast cancer, the FDA and the healthcare data and analytics company created a study protocol to guide approaches to handling treatment within subpopulations.⁶

COTA is a technology company founded by oncologists and data scientists on the idea that harnessing the vast amounts of information from disorganized EHRs will enable data interpretation so that doctors can relate these findings toward current patients with cancer. In the August issue of Evidence-Based Oncology™, COTA Chief Medical Officer Andrew Norden, MD, MPH, MBA, highlighted the steps being taken within the FDA’s partnership to work in populations that are often excluded from clinical trials.⁷

The use of EHRs and RWE to combat racial disparity in clinical trials is providing innovative steps to include underrepresented races, like black and Hispanic patients, in their data. Through the ongoing effort by the FDA and COTA to correct race representation, doctors can understand what cancer treatments are best for their patients.

“Real-world evidence is one of many tools that we can use to help address variation in subpopulations and to learn more about how to best utilize cancer treatments to improve outcomes in patients,” said Loree. References

1. 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 [published online August 15, 2019]. JAMA Oncology. doi: 10.1001/jamaoncol.2019.1870.

2. Dean LT, Gehlert S, Neuhouser ML, et al. Social factors matter in cancer risk and survivorship. Cancer Causes & Control. 2018;29(7):611-618. doi: 10.1007/s10552-018-1043-y.

3. Study finds lack of racial diversity in cancer drug clinical trials [press release]. Vancouver, British Columbia: UBC News; August 16, 2019. news.ubc.ca/2019/08/16/study-finds-lack-ofracial-diversity-in-cancer-drug-clinical-trials/. Accessed September 11, 2019.

4. Framework for FDA’s real-world evidence program. FDA website. www.fda.gov/media/120060/download. Published December 2018. Accessed August 21, 2019.

5. Zegarelli BM. 21st Century Cures Act requires FDA to expand the role of real world evidence. Mintz website. mintz.com/insights-center/viewpoints/2146/2016-12-21st-century-cures-actrequires-fda-expand-role-real-world. Published December 19, 2016. Accessed August 21, 2019.

6. COTA Healthcare website. cotahealthcare.com. Accessed August 21, 2019.

7. Norden A, Caffrey M. COTA collaboration: helping FDA figure out what’s possible, what’s not in embrace of real-world evidence. Am J Manag Care. 2019;25(SP9):SP266-SP268

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