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.