Naveed Saleh, MD, MS, for MDLinx | September 06, 2019
It may be surprising to learn that the rate of human genetic variation secondary to differences between populations (ie, races) is small. Moreover, people of different races can be more genetically similar to each other than people of the same race.
Nevertheless, ample genetic data support the accurate classification of people into different racial populations. And in the case of clinical trials, this distinction is important, especially in the current era of personalized and precision medicine.
A dearth of racial representation occurs across all clinical trials—not only those assessing lung cancer—but disparities have long been observed in lung cancer treatment among racial and ethnic minorities. And with lung cancer leading the charge with cancer mortality among men and women in the United States and worldwide, this underrepresentation is, indeed, troubling.
Let’s start with the more general lack of diversity and then move to the more specific lack of diversity in lung cancer trials.
Black and Hispanic races are underrepresented in major clinical trials, according to the results of a retrospective study published in JAMA Oncology.
“Racial diversity in clinical trials serves as a metric of societal equality and access to healthcare, while also allowing assessment of biologic differences that may determine differential efficacy of drugs,” wrote the authors, led by Jonathan M. Loree, MD, BC Cancer, Vancouver, British Columbia, Canada. “This is particularly important in racially pluralistic societies such as the United States because studies have demonstrated survival differences from cancer by race, even after controlling for socioeconomic and treatment differences.”
In this study, Dr. Loree and colleagues examined the frequency of race reporting and race representation between July 2008 and June 2018 in 230 trials (n = 112,293) supporting the FDA approval of oncology drugs. Notably, cancer estimates by race were based on National Cancer Institute (NCI)–Surveillance, Epidemiology, and End Results (SEER) and US Census databases.
Participant race was recorded in only 145 (63%) trials. From July 2008 to June 2013 vs July 2013 to June 2018, the rate of trials noting race changed minimally (56.6% vs 67.1%, respectively). Moreover, the number of trials reporting race subgroups also changed minimally. White, Asian, Hispanic, and black individuals constituted 76.3%, 18.3%, 6.1%, and 3.1% of participants, respectively, with proportions changing little from July 2008 to June 2013 vs July 2013 to June 2018.
When compared with proportions of US cancer incidence, black individuals represented only 22% of the value expected; Hispanic individuals, 44%; and whites individuals, 98%. Asian individuals bucked the trend with a representation that was 438% of what was expected.
Lack of diversity in cancer trials also keeps minorities from benefiting from scientific advances, and decreases the generalizability of trial results. Furthermore, genetic variation by race may be important in determining drug metabolism and response. Trials need to analyze racial variations in drug metabolism and biomarker frequency. Issues with trial inclusivity have been addressed by the NIH and FDA, with unclear benefit.
With respect to specific differences, the proportion of key driver mutations, including epidermal growth factor receptor mutations observed in lung cancer, range widely across races. Moreover, in similar trials with uniform characteristics, black participants seem to harbor increased intratumor genetic heterogeneity and decreased survival compared with their white counterparts.
“This finding suggests an underlying biological connotation to the social construct of race and indicates a need to understand this complexity,” stated the authors.
Various roadblocks could play a role in the underrepresentation of certain populations in clinical trials, including the fact that although some racial groups may view clinical trials state of practice, other groups perceive their participation as exploitation (recall the Tuskegee syphilis study). Other barriers included distance to treatment, means of transportation, and lower incomes. Specifically, in 2017, the median US household income was most for Asian people ($81,331), followed by white ($68,145), Hispanic ($50,486), and black individuals ($40,258).
Dr. Loree and fellow researchers acknowledged that, although it is hard to prospectively ensure race participation, certain steps can be taken in this direction. These steps include smaller, targeted follow-up studies; taking phase 4 data from an underrepresented group; and posting data to publicly accessible portals, such as Project Data Sphere, that can help further elucidate race-specific analysis.
Enrollment disparity is common in lung cancer trials, too, according to the results of a study published in the Journal of Clinical Oncology. In this high-power study, investigators mined the SEER database for NCI-funded lung-cancer trials from 1990 to 2012. They discovered that, although disparities in these trials decreased for older patients and women, they persisted among black and Hispanic individuals, as well as for Asian/Pacific Islanders. Of note, any improvements in boosting enrollment may be due to changes in specific trial characteristics and policy changes.
Finally, in an editorial published in the Annals of Translational Medicine, researchers explained that the issue of under-enrollment is nothing new, and recommended the following:
“Improving enrollment of under-represented populations in cancer treatment trials will require changes ranging from the individual level to funding priorities and policies. The need persists for concerted efforts to identify and address common patient barriers to participation. Providing trial access in rural communities and building trust within under-represented groups is crucial. Increasing patient engagement in trial design and routine assessment of patient-reported measures may increase enrollment.”