4. Discussion
Our study is the first one to look at the reporting trends in race and sex in phase III lung cancer trials over last 35 years. The results of our analysis further substantiate the evidence that continues to highlight the disparities surrounding race in clinical trials.
Examining the trends in reporting of sex, we find more positive change over time. In the studies we reviewed, 98.8% reported participant sex. Analyzing these trends, we noted progressive increase in women representation since 1985. While the trends over time are promising, females are still underrepresented with a mean participation rate of 34.97% from 2015-2019. This is despite females accounting for 48.9% of lung cancer in the United States [13]. Similar patterns have also been seen in other, non-cancer clinical trials as well. For example, cardiovascular and lipid lowering agent clinical trials also showed underrepresentation of females at a participation rate of 33%-38% [14, 15].
We were surprised to find that no phase III lung cancer study, in our database, between 1984-1992 reported on race. In reviewing the literature for evidence, we encountered significant variability in race reporting across different studies. As an example, Brahan et al. found significant increases in race reporting from 29.6% to 63.5% in pediatric studies conducted in 1991-1993 and 2000-2002 [16]. In a 2011 study, Geller et al. looked at 86 clinical trials across nine high-impact journals and found that one-fifth of the studies failed to report the distribution of participant race [17]. Unlike the findings from these studies, our findings showed that a significantly larger proportion of lung cancer phase III clinical trials did not report the distribution of participant race. There can be several reasons for such degree of variance. Pediatric clinical studies, especially pediatric oncology studies, have more centralized review and sponsoring processes, and are more likely to be funded by the NIH. Logically, such studies are more likely to comply with the NIH policies including the provisions of the NIH Revitalization Act and hence the significant change in the race and sex reporting as noted by Brahan et al. This increase in race reporting, while encouraging, falls short of the ideal as a third of pediatric oncology studies still did not report race as a variable. Another reason for lack of reporting on race may be that majority of the studies are multinational in nature and may include geographical areas with less cultural heterogeneity. This is likely an important limitation of our study. However, the rapid globalization and human migration over the last two decades calls for a more acute evaluation. The results of our study in the context of recent demographic changes highlight the significance of addressing this trend as health inequality and disparities are becoming more of a global issue.
Our findings of minority underrepresentation in lung cancer phase III clinical trials have also been observed in other studies as well. A 2004 study looking at race-based disparities in cancer clinical trials also found White participants to represent 85.6% of all participants and another study found White participants to represent 76.3% of all participants in cancer drug clinical trials [4, 18]. One might question the generalizability of this finding in the context of the demographic make-up of the population and the epidemiology of the disease under study. For lung cancer, this is especially important as the incidence in African Americans, the largest minority population in the United States, is 59.5 per 100,000 compared to 61.6 per 100,000 in Whites [13]. Loree et al in 2019 evaluated the reporting of race and other demographic variables in the landmark clinical trials leading to the approval of antineoplastic therapies and found a similar finding of decline in African American participation between 2008 and 2018 [18].
The principles of justice, beneficence and the medicine’s professional code of conduct require diversity and inclusion as mission critical to its social contract with the society. These higher moral values call out for all efforts to ensure adequate access of all segments of society to the benefits of biomedical research. While it may be debatable that non-reporting is not synonymous with not-being included, it is strong enough evidence to support the conclusion of non-inclusion. Although positive changes have been made in the reporting of sex, there is clearly room for much improvement when it comes to the reporting of race. The responsibility to move the needle forward falls on shoulders of all stakeholders. The clinicians and patient care teams should review and discuss the importance of race and sex reporting with the patients in the broader context of its value to the society and in addressing the disparities. The clinical trials’ sponsors should work with the study teams to ensure recording sex and race amongst other demographic information in case report forms. The medical publishers should mandate the reporting of race and sex as a criterion for acceptance of publication.
Our study does have limitations . Given that this study was a retrospective analysis, it carries the same weaknesses associated with such studies. As noted in the methods section, we could not reliably decipher which studies were solely U.S. based versus from other regions as majority of the manuscripts had author affiliations from various institutions across the globe.