Vascular surgeons treat a diverse patient population and Level I evidence derived from RCT guides the standard of surgical care based on representative sampling of that population. In this study we have shown that complete demographic reporting of gender and race/ethnicity is absent from a large portion of vascular surgery RCT conducted in the U.S. Complete demographic reporting, particularly for ethnicity, was associated with larger, multicenter and/or government funded trials. There does not appear to be significant increases in reporting over time, particularly in the years following the NIH Revitalization Act of 1993. Among studies reporting gender and ethnicity data, women were significantly underrepresented in clinical trials for aortic, lower extremity and carotid artery procedures, while ethnic minorities were underrepresented in RCT involving aortic aneurysms and carotid revascularization.
The underreporting and underrepresentation of women and minorities occurs in a broad array of clinical research across multiple specialties. Even in specialties with known health disparities between gender and ethnicity, such as in diabetes, cardiac disease, HIV and cancer, there is persistent underreporting of complete demographic data in clinical research.16
There is also a demonstrated underrepresentation of women and minorities in clinical trials as well as underutilization of women and minorities in statistical models aimed at better understanding the disparities in disease prevalence and outcomes.17
Oddone, et al. evaluated trials containing an invasive arm and demonstrated that most enrolled fewer minority patients than expected. Interestingly, this same study showed that a majority of trials for diseases with disproportionate minority prevalence (diabetes, hypertension, end stage renal disease) enrolled more minority subjects than expected.18
As we have noted, PAD is more prevalent in AA and HA. As such, our study corroborates Oddone's findings in RCT of LER where minority enrollment exceeded estimated procedure frequency. One potential explanation for this over-representation may be that many RCT occur at large academic institutions that already care for a larger number of minority patients. Thus, the pool of trial participants is already over-represented in these institutions.
Significant consideration has been given to the causes of underrepresentation of minorities and women in RCT. There is a long-held belief that ethnic minorities are less willing to participate in human and clinical research, attributed to a mistrust of the medical and scientific community stemming from the Tuskegee syphilis and other similar experiments widely publicized in the media.19
However, this notion has become increasingly controversial as multiple recent studies have demonstrated equivalent willingness to participate in clinical trials regardless of ethnicity.20
Despite this, it is reported that minorities are more likely to believe that they had been previously treated in a trial without their consent.21
This suggests a persistent element of differing expectations and mistrust that needs to be overcome. In contrast, women, particularly those of child bearing age, have a long history of being excluded from RCT. Historically, this, in part, stems from a desire to limit the exposure of women of child bearing age to experimental treatments.22
However, with the recognition that gender is an important variable in the manifestation of disease and in the response to treatment, there has been significant effort toward balanced enrollment by gender into clinical trials. That there remains a persistent disparity in representation of women in a broad spectrum of clinical trials suggests the interplay of multiple subtle factors both in society and in clinical trial design and execution.23
Several limitations are present in this study. First, race/ethnicity is self-reported in RCT and in the NIS database. Furthermore, race/ethnicity is a complex topic with significant contributions from the fields of genetics, sociology, anthropology, and history. Not all minorities share similar backgrounds making broad categorization difficult, especially considering immigration patterns in the U.S. Despite these inherent difficulties in defining race/ethnicity, studies should at least try to report this important demographic in some manner. Presumably, gender is a more straightforward demographic variable to evaluate, yet many studies do not even report this data. It is possible that the studies not reporting gender or ethnicity may in fact have over-representation of these groups and thus the overall RCT enrollment distribution may be appropriate. However, when important demographic information is not available, no meaningful conclusions can be made.
Second, appropriate trial design may necessitate exclusion of portions of the population that have significant minority or gender representation. For example, end-stage renal disease is frequently a component of the exclusion criteria of vascular surgery RCT and it disproportionately affects AA.24, 25
As such, the goal of developing accurate endpoint measurement may have the unintended, and potentially unavoidable, consequence of under-representing specific patient populations.
Third, enrollment results are not entirely under the control of researchers. Very few RCT can draw enrollment from a nationally representative patient population. Even for multi-center studies, the local institutions conducting the trial may have distinct referral patterns. In particular, the VA patient population is not representative of the U.S. population in that it under represents women. However, many high quality vascular surgery RCT that guide clinical decision-making come from VA collaborations. Our sub-analysis excluding VA studies demonstrated attenuated disparities in enrollment. A more balanced incorporation of the VA population into the main analysis would require access to VA population and procedural data not available to the authors. Furthermore, with the increasing military enlistment of women and minorities in recent decades, the current veteran population may be more demographically similar to the entire U.S. population than in previous times.
Finally, the limited number of studies available in each category does not lend themselves to more sophisticated statistical measures. Because many of the parameters examined were strongly co-associated (for example, large trials and multi-center trials consisted of overlapping groups), multivariate logistic regression did not yield interpretable results and were therefore left out of this analysis.
In spite of these limitations, this study clearly demonstrates under-reporting of gender and race/ethnicity as well as disparities in the enrollment of women and minorities in vascular surgery RCT. This has significant implications for the interpretation and generalizability of these studies to the overall population. Recognition of these limitations may help surgeons assimilate other studies with better representation for their patient population. The authors of this study do not imply that the disparities in reporting and enrollment are intentional. Rather, patient concerns, unrecognized bias, and local population demographics likely contribute to these disparities. Nevertheless, this issue should be highlighted to promote compliance to NIH regulations in future studies. Further, in the interest of better understanding out diverse patient population, we feel these regulations should extend to all vascular surgery clinical studies, not just those funded by the NIH. With this recognition, researchers can focus on identifying and improving barriers to balanced recruitment and retention appropriate for their local environment. Such strategies can include focused recruitment and education about clinical research ethics and safeguards, recruitment of institutions with intrinsic minority representation into multi-center trials, and recruitment goals/caps based on estimates of disease incidence or procedural frequency.