This cohort study identifies differences in the racial, ethnic, and socioeconomic characteristics of patient populations among candidate sites in the US that did vs did not participate in clinical trials for novel transcatheter valve therapies.
Key Points
Question
What are the racial, ethnic, and socioeconomic characteristics of patients treated at sites that participate in clinical trials for novel transcatheter valve therapies compared with candidate sites that do not participate in these trials?
Findings
In this cohort study of 1050 hospitals, patients treated in trial hospitals were more socioeconomically advantaged than patients treated at nontrial hospitals. There was no meaningful difference in the proportion of Black and Hispanic patients at trial vs nontrial hospitals.
Meaning
Site selection may improve socioeconomic diversity in clinical trials for transcatheter valves but may not improve racial and ethnic diversity.
Abstract
Importance
Racial and ethnic minority and socioeconomically disadvantaged patients have been underrepresented in randomized clinical trials. Efforts have focused on enhancing inclusion of minority groups at sites participating at clinical trials; however, there may be differences in the patient populations of the sites that participate in clinical trials.
Objective
To identify any differences in the racial, ethnic, and socioeconomic composition of patient populations among candidate sites in the US that did vs did not participate in trials for novel transcatheter therapies.
Design, Setting, and Participants
This cross-sectional analysis used Medicare Provider Claims from 2019 for patients admitted to hospitals in the US. All clinical trials for transcatheter mitral and tricuspid valve therapies and the hospitals participating in each of the trials were identified using ClinicalTrials.gov. Hospitals with active cardiac surgical programs that did not participate in the trials were also identified. Data analysis was performed between July 2021 and July 2022.
Exposures
Multivariable linear regression models were used to identify differences in racial, ethnic, and socioeconomic characteristics among patients undergoing cardiac surgery or transcatheter aortic valve replacement at trial vs nontrial hospitals.
Main Outcome and Measures
The main outcome of the study was participation in a clinical trial for novel transcatheter mitral or tricuspid valve therapies.
Results
A total of 1050 hospitals with cardiac surgery programs were identified, of which 121 (11.5%) participated in trials for transcatheter mitral or tricuspid therapies. Patients treated in trial hospitals had a higher median zip code–based household income (difference of $5261; 95% CI, $2986-$7537), a lower Distressed Communities Index score (difference of 5.37; 95% CI, 2.59-8.15), and no significant difference in the proportion of patients dual eligible for Medicaid (difference of 0.86; 95% CI, −2.38 to 0.66). After adjusting for each of the socioeconomic indicators separately, there was less than 1% difference in the proportion of Black and Hispanic patients cared for at hospitals participating vs not participating in clinical trials.
Conclusions and Relevance
In this cohort study among candidate hospitals for clinical trials for transcatheter mitral or tricuspid valve therapies, trial hospitals took care of a more socioeconomically advantaged population than nontrial hospitals, with a similar proportion of Black and Hispanic patients. These data suggest that site selection efforts may improve enrollment of socioeconomically disadvantaged patients but may not improve the enrollment of Black and Hispanic patients.
Introduction
Racial and ethnic minority and socioeconomically disadvantaged patients have been underrepresented in randomized clinical trials.1,2 Underrepresentation limits clinicians’ ability to apply the findings of major clinical trials to these patients and may contribute to limiting their access to novel, experimental therapies after their ultimate regulatory approval.3,4,5 To address inequities in trial enrollment, the National Institutes of Health (NIH) Revitalization Act of 1993 mandated appropriate inclusion of racial and ethnic minority groups; however, representativeness remains a problem for clinical trials, including both industry-funded and NIH-funded trials enrolling patients with cardiovascular conditions.6,7,8,9,10 In 1 review of 143 clinical trials conducted between 2008 and 2017 to evaluate 35 novel cardiometabolic drugs, just 2.1% of enrollees were Black and 2.1% were Hispanic.11
Efforts from the NIH and the US Food and Drug Administration have focused on enhancing inclusion of minority groups at sites participating at clinical trials; however, another factor that may limit representation of racial and ethnic minority groups and socioeconomically disadvantaged patients in clinical trials is the characteristics of the hospitals that most often participate as clinical trial sites and enroll patients.12 If hospitals that participate in clinical trials take care of relatively few patients from racial and ethnic minority groups and/or socioeconomically disadvantaged patients, this would represent a systemic barrier to trial access for these populations.
Transcatheter therapies to treat mitral and tricuspid valve disease are not yet standard of care in most circumstances but are an area of rapid development with multiple ongoing industry-sponsored clinical trials. In this study, we sought to identify the characteristics of sites that participate in clinical trials for novel transcatheter tricuspid and mitral valvular therapies among candidate hospitals with active cardiac surgery programs. We specifically aimed to identify any differences in the racial, ethnic, and socioeconomic composition of patient populations among candidate sites in the US that did and did not participate in these trials.
Methods
Study Cohort
This study was deemed to be exempt by the institutional review board at the University of Pennsylvania due to the use of deidentified data, and informed consent was waived due to institutional policy for deidentified administrative data. The Medicare Provider Analysis and Review data files and the Master Beneficiary Summary data files were used to identify Medicare fee-for-service beneficiaries aged 66 years or older who were admitted to hospitals with existing cardiac surgery programs between January 1, 2019, and December 31, 2019. To identify representative patients undergoing cardiovascular and cardiac surgical procedures at these hospitals, Medicare beneficiaries undergoing cardiac surgery procedures or transcatheter aortic valve replacement (TAVR) during this period were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision procedure codes. We used an age cutoff of 66 years to ensure a minimum 12-month preoperative period to assess comorbidities. Hospitals were considered to have an active cardiac surgery program if they coded for 10 or more major cardiac surgery procedures in 2019. We chose 10 procedures to minimize the effect of administrative coding errors at the hospital level (eFigure in the Supplement).
Trial hospitals for transcatheter tricuspid and mitral valvular therapies were identified using ClinicalTrials.gov. ClinicalTrials.gov was queried on September 30, 2021, for the terms transcatheter tricuspid valve repair, transcatheter tricuspid valve replacement, transcatheter mitral valve repair, and transcatheter mitral valve replacement. Trial hospitals were identified, and the Centers for Medicare & Medicaid Services certification number obtained from the Medicare Inpatient Hospital Look-up Tool from 2018.13
The terms transcatheter aortic valve replacement and transcatheter aortic valve repair were not queried given the establishment of transcatheter aortic valve replacement as the treatment modality of choice for the majority patients with aortic stenosis. We did not investigate transcatheter pulmonary valve replacement and transcatheter pulmonary valve repair because these therapies are predominantly used among pediatric and adolescent patients rather than the older adult population.
Geographic Identification
Patient and hospital zip code information was obtained from the Hospital Data Claims and Demographic Data files. Patients and hospitals were assigned to Core-Based Statistical Areas using zip code information from US Department of Housing crosswalk files using 2010 Census geographies, as described previously.14 The US Office of Management and Budget defines metropolitan areas as urban clusters of at least 50 000 people and micropolitan areas as urban clusters of between 10 000 and 50 000 people. Zip codes that were not linked to metropolitan or micropolitan Core-Based Statistical Areas were defined as rural.
Race, Ethnicity, and Socioeconomic Identification
Race and ethnicity were defined as per the Master Beneficiary Summary data files. Existing categories were Asian, Black, Hispanic, White, other, and unknown. For the purposes of this analysis, since the categories were mutually exclusive, we will use Black to refer to non-Hispanic Black individuals and White to refer to non-Hispanic White individuals throughout.
Socioeconomic status of Medicare fee-for-service patients was defined using 3 measures, as described previously.14 Median household income for each patient was assessed using patient zip code data cross-linked with the Dartmouth Atlas.15 Dual-eligibility status for Medicaid for each patient was assessed using Medicare Denominator files.16 The Distressed Communities Index (DCI) score for each patient was obtained using patient zip code data and crosswalk files for DCI data between 2012 and 2016.17 The DCI combines 7 economic indicators (percentage of population with high school diploma, housing vacancy rate, percentage of adults not working, poverty rate, median income ratio, change in employment, and change in business establishments) to generate a single index score, with a range from 0 (least distressed) to 100 (most distressed).
Statistical Analysis
Characteristics of hospitals with cardiac surgery programs that participated in transcatheter tricuspid and mitral valvular trials were compared with hospitals that did not participate in trials using the t test to compare means and χ2 analysis to compare proportions, as appropriate. Similarly, baseline clinical, demographic, and socioeconomic characteristics of patients who underwent cardiac surgery or TAVR between 2016 and 2019 at hospitals that participated in transcatheter valvular trials were compared with those of patients treated in hospitals that did not participate in trials using the t test to compare means and χ2 analysis to compare proportions, as appropriate.
To estimate the associations between participation in clinical trials among cardiac surgery hospitals and hospital location (metropolitan, micropolitan, rural), proportion of Black or Hispanic patients treated at each hospital, and the socioeconomic characteristics of patients undergoing cardiac surgery or TAVR at each hospital, 3 separate multivariable linear regression models were generated, with hospital characteristic variables and patient characteristics aggregated at the hospital level. Each model included only 1 socioeconomic indicator (median household income, proportion of dual eligibility for Medicaid, mean DCI score) to avoid collinearity.
As secondary analyses, we determined the clinical and demographic characteristics of all Medicare beneficiaries at the studied hospitals and repeated the above analyses. Statistical analyses were performed using SAS, version 9.4 (SAS Institute) and R Studio, version 1.3.959 (R Foundation). All statistical testing was 2-tailed, with P values less than .05 designated statistically significant.
Results
We identified 1050 active cardiac surgical programs between January 1, 2019, and December 31, 2019. There were 32 unique clinical trials for transcatheter mitral and tricuspid valve therapies (10 transcatheter mitral valve repair, 10 transcatheter mitral valve replacement, 6 transcatheter tricuspid valve repair, 6 transcatheter tricuspid valve replacement). Only 4 of the 32 trials had demographic data of trial participants available on ClinicalTrials.gov. Among those 4 trials, proportions of Black trial participants ranged from 0% to 16.7%, and proportions of Hispanic trial participants ranged from 3.3% to 6.9%. A list of all included trials is provided in eTable 1 in the Supplement. Of the 1050 hospitals with cardiac surgery programs, 121 (11.5%) participated in 1 or more trial of transcatheter mitral or tricuspid therapies. Among the 121 trial hospitals, the median (IQR) hospital participated in 3 (2-5) trials. Details on mitral and tricuspid valve procedures performed at trial and nontrial hospitals during the study period are provided in eTable 2 in the Supplement. Geographical maps of sites that participated in clinical trials for percutaneous mitral or tricuspid valve therapies were generated (Figure).
Figure. US Trial and Nontrial Cardiology Hospitals.
Geographic map of hospitals with cardiac surgery programs that did or did not participate in clinical trials for transcatheter mitral and tricuspid valve therapies between January 1, 2019, and December 31, 2019.
Trial hospitals for percutaneous mitral or tricuspid valve therapies were larger (79.3% vs 30.4% with greater than 400 beds; P < .001) and were more likely to be academic centers (61.2% vs 16.6%; P < .001) (Table 1). Trial hospitals were more likely to be in metropolitan areas (99.2% vs 94.8%; P = .03). Further, patients undergoing cardiac surgery or TAVR at trial hospitals tended to have higher rates of clinical comorbidities than patients undergoing cardiac surgery or TAVR at nontrial hospitals (Table 2).
Table 1. Characteristics of Hospitals With Cardiac Surgery Programs That Did and Did Not Participate in Clinical Trials for Transcatheter Mitral and Tricuspid Valve Therapies.
| Variable | No. (%) | P value | |
|---|---|---|---|
| Nontrial hospitals (n = 929) | Trial hospitals (n = 121) | ||
| Bed size | |||
| <100 Beds | 23 (2.5) | 2 (1.7) | <.001 |
| 100-399 Beds | 624 (67.2) | 23 (19.0) | |
| ≥400 Beds | 282 (30.4) | 96 (79.3) | |
| Teaching hospital | 154 (16.6) | 74 (61.2) | <.001 |
| Profit status | |||
| For-profit | 181 (19.5) | 16 (13.2) | .19 |
| Nonprofit | 651 (70.1) | 94 (77.7) | |
| Government | 97 (10.4) | 11 (9.1) | |
| Region | |||
| Midwest | 249 (26.8) | 25 (20.7) | .11 |
| Northeast | 115 (12.4) | 24 (19.8) | |
| South | 363 (39.1) | 47 (38.8) | |
| West | 202 (21.7) | 25 (20.7) | |
| Area | |||
| Metropolitan | 881 (94.8) | 120 (99.2) | .03 |
| Nonmetropolitan | 48 (5.2) | 1 (0.8) | |
Table 2. Characteristics of Patients Undergoing Cardiac Surgery or TAVR at Hospitals That Did and Did Not Participate in Clinical Trials for Transcatheter Mitral and Tricuspid Valve Therapies.
| Variable | No. (%) | P value | |
|---|---|---|---|
| Patients treated in nontrial hospitals (n = 334 453) | Patients treated in trial hospitals (n = 154 369) | ||
| Age, mean (SD), y | 74.9 (6.6) | 76.1 (7.2) | <.001 |
| Sex | |||
| Female | 113 458 (33.9) | 56 984 (36.9) | <.001 |
| Male | 220 995 (66.1) | 97 385 (63.1) | |
| Race and ethnicity | |||
| Asian | 5413 (1.6) | 3072 (2.0) | <.001 |
| Black | 14 294 (4.3) | 6889 (4.5) | |
| Hispanic | 14 481 (4.3) | 6.028 (3.9) | |
| White | 291 577 (87.2) | 134 282 (87.0) | |
| Othera | 4125 (1.2) | 1745 (1.1) | |
| Unknown | 4563 (1.4) | 2353 (1.5) | |
| Region | |||
| Midwest | 84 186 (25.2) | 32 793 (21.2) | <.001 |
| Northeast | 56 752 (17.0) | 39 390 (25.5) | |
| South | 135 123 (40.4) | 57 966 (37.6) | |
| West | 58 392 (17.5) | 24 220 (15.7) | |
| Patient residence | |||
| Metropolitan | 259 243 (77.5) | 129 468 (83.9) | <.001 |
| Nonmetropolitan | 75 210 (22.5) | 24 901 (16.1) | |
| Median household income, median (IQR), $ | 50 498 (40 142-65 422) | 57 966 (44 034-79 215) | <.001 |
| DCI score, median (IQR) | 44.3 (20.4-70.8) | 31.1 (13.6-58.7) | <.001 |
| Dual eligibility for Medicaid | 20 632 (6.2) | 8657 (5.6) | <.001 |
| Elixhauser Comorbidity Score, mean (SD) | 6.2 (3.2) | 6.6 (3.2) | <.001 |
| Comorbidities | |||
| Heart failure | 175 917 (52.6) | 96 580 (62.6) | <.001 |
| Hypertension | 314 071 (93.9) | 144 684 (93.7) | .02 |
| Diabetes | 152 870 (45.7) | 65 177 (42.2) | <.001 |
| Stroke | 16 227 (4.9) | 7860 (5.1) | <.001 |
| Peripheral vascular disease | 92 251 (27.6) | 47 220 (30.6) | <.001 |
| Kidney disease | 111 504 (33.3) | 55 070 (35.7) | <.001 |
| Liver disease | 15 389 (4.6) | 8067 (5.2) | <.001 |
Abbreviations: DCI, Distressed Communities Index; TAVR, transcatheter aortic valve replacement.
“Other” is used per the Centers for Medicare & Medicaid Services data files.
In unadjusted models, compared with patients undergoing cardiac surgery or TAVR for at nontrial hospitals, patients undergoing cardiac surgery or TAVR at trial hospitals resided in zip codes with higher median (IQR) income ($57 966 [$44 034-$79 215] vs $50 498 [$40 142-$65 422]; P < .001) and lower levels of community distress (median [IQR] DCI score, 31.1 [13.6-58.7 vs 44.3 [20.4-70.8]; P < .001) and were less often dual eligible for Medicaid (5.6% vs 6.2%; P < .001) (Table 2). We found similar results when studying the socioeconomic characteristics of all Medicare beneficiaries at trial vs nontrial hospitals, although trial hospitals treated a higher proportion of Black patients among total beneficiaries compared with nontrial hospitals (9.7% vs 8.0%; P < .001) (Table 3).
Table 3. Patient Characteristics Among All Medicare Beneficiaries Admitted to Sites Between 2016 and 2019 That Did or Did Not Participate in Clinical Trials for Transcatheter Mitral and Tricuspid Valve Therapies.
| Variable | No. (%) | P value | |
|---|---|---|---|
| Patients admitted to nontrial hospitals (n = 7 798 324) | Patients admitted to trial hospitals (n = 1 845 297) | ||
| Age, mean (SD), y | 77.4 (8.2) | 76.8 (8.1) | <.001 |
| Sex | |||
| Female | 4 197 226 (53.8) | 958 450 (51.9) | <.001 |
| Male | 3 601 098 (46.2) | 886 847 (48.1) | |
| Race and ethnicity | |||
| Asian | 162 151 (2.1) | 46 451 (2.5) | <.001 |
| Black | 621 308 (8.0) | 178 291 (9.7) | |
| Hispanic | 393 700 (5.0) | 93 194 (5.1) | |
| White | 6 452 666 (82.7) | 1 479 903 (80.2) | |
| Othera | 93 325 (1.2) | 20 723 (1.1) | |
| Unknown | 75 174 (1.0) | 26 735 (1.4) | |
| Region | |||
| Midwest | 2 046 133 (26.2) | 404 531 (21.9) | <.001 |
| Northeast | 1 093 522 (14.0) | 466 924 (25.3) | |
| South | 3 229 663 (41.4) | 703 778 (38.1) | |
| West | 1 429 006 (18.3) | 270 064 (14.6) | |
| Patient residence | |||
| Metropolitan | 6 479 885 (83.1) | 1 622 535 (87.9) | <.001 |
| Nonmetropolitan | 1 318 439 (16.9) | 222 762 (12.1) | |
| Median household income, median (IQR), $ | 50 917 (40 111-66 062) | 57 725 (43 189-78 568) | <.001 |
| Distressed Communities Index score, mean (SD) | 45.8 (29.0) | 37.6 (27.8) | <.001 |
| Dual eligibility for Medicaid | 984 458 (12.6) | 201 927 (10.9) | <.001 |
| Elixhauser Comorbidity Score, mean (SD) | 12.22 (13.09) | 12.26 (13.34) | <.001 |
| Comorbidities | |||
| Heart failure | 2 274 190 (29.2) | 523 807 (28.4) | <.001 |
| Hypertension | 6 493 140 (83.3) | 1 506 613 (81.6) | <.001 |
| Diabetes | 2 646 785 (33.9) | 585 275 (31.7) | <.001 |
| Stroke | 323 191 (4.1) | 60 003 (3.3) | <.001 |
| Peripheral vascular disease | 1 113 069 (14.3) | 270 164 (14.6) | <.001 |
| Kidney disease | 2 078 343 (26.7) | 465 948 (25.3) | <.001 |
| Liver disease | 375 208 (4.8) | 96 636 (5.2) | <.001 |
“Other” is used per the Centers for Medicare & Medicaid Services data files.
Differences in the racial, ethnic, and socioeconomic characteristics of patients undergoing cardiac surgery or TAVR in trial and nontrial hospitals are summarized in Table 4. After adjusting for hospital and patient clinical characteristics, patients undergoing cardiac surgery or TAVR at trial hospitals had higher median zip code–based household income than patients treated in nontrial hospitals (difference of $5261; 95% CI, $2986-$7537; P < .001). Patients at trial hospitals also lived in less distressed communities (difference in mean DCI score of 5.37; 95% CI, 2.59-8.15; P < .001). However, there was no significant difference in the proportion of patients dual eligible for Medicaid between trial and nontrial hospitals (difference of 0.86; 95% CI, −2.38 to 0.66; P = .27).
Table 4. Differences in Racial, Ethnic, and Socioeconomic Status Among Patients Undergoing Cardiac Surgery or TAVR in Trial vs Nontrial Hospitals Adjusted for Hospital, Demographic, and Clinical Characteristics.
| Variable | Difference between trial and nontrial hospitals (95% CI) | P value |
|---|---|---|
| Median household income, $ | 5261 (2986 to 7537) | <.001 |
| Proportion Black patients, % | 0.09 (−0.01 to 0.18) | .06 |
| Proportion Hispanic patients, % | 0.02 (−0.03 to 0.09) | .36 |
| Mean DCI score | −5.37 (−8.41 to −2.59) | <.001 |
| Proportion Black patients, % | 0.12 (0.01 to 0.23) | .03 |
| Proportion Hispanic patients, % | 0.03 (−0.04 to 0.10) | .47 |
| Proportion dual eligible for Medicaid, % | −0.86 (−2.38 to 0.66) | .26 |
| Proportion Black patients, % | 0.38 (0.34 to 0.43) | <.001 |
| Proportion Hispanic patients, % | 0.39 (0.34 to 0.43) | <.001 |
Abbreviations: DCI, Distressed Communities Index; TAVR, transcatheter aortic valve replacement.
In both unadjusted and adjusted models, there was less than 1% difference in the proportion of Black and Hispanic patients cared for at hospitals participating and not participating in clinical trials (Table 4). Similar findings were seen when studying all Medicare beneficiaries at trial vs nontrial hospitals (eTable 3 in the Supplement).
Discussion
In this cohort study, we sought to identify whether site selection may be associated with inequities in randomized clinical trial participation by race, ethnicity, and socioeconomic status by describing differences in the racial, ethnic, and socioeconomic composition of the patient populations of hospitals that participated in clinical trials for transcatheter valvular therapies vs candidate hospitals that did not. We found that hospitals that participated in trials for transcatheter mitral and tricuspid valve therapies cared for a patient population that was socioeconomically more advantaged than the patient population of hospitals that did not participate in trials. However, they also cared for a population that had similar proportions of Black and Hispanic patients. These data would suggest that broader inclusion of potential clinical trial sites may improve access to clinical trials among socioeconomically disadvantaged patients, but may not improve the enrollment of Black and Hispanic patients. Given the inequities that have been well documented in cardiovascular clinical trials, these data would suggest that hospitals currently participating in clinical trials for structural heart disease need to actively engage Black and Hispanic communities to improve enrollment in clinical trials.
Surgical treatment has been the standard of care for patients with mitral and tricuspid pathology who require intervention. However, the surgical treatment of valvular heart disease is invasive and may not be an option for patients who have clinical comorbidities that put them at high risk or prohibitive risk for adverse events around the time of surgery. Advances in percutaneous therapies for mitral and tricuspid repair and replacement are less invasive and may provide treatment options for those patients who may otherwise die of their valvular heart disease.18,19,20
We have previously shown that the initial growth in the availability of novel commercial therapies may not be equally afforded to all segments of the population.4,21 With TAVR, a transformative device therapy for the treatment of patients with severe symptomatic aortic stenosis, we found that sites that adopted this technology after US Food and Drug Administration approval were predominantly in metropolitan areas that took care of socioeconomically more advantaged patients.14 Further, within metropolitan areas with several centers performing TAVR, we found that areas with higher proportions of Black, Hispanic, and socioeconomically disadvantaged patients had lower age-adjusted rates of TAVR, suggesting the presence of inequities in access to this procedure.5
The current study aimed to build on these prior findings by examining potential inequities in access to novel and experimental valvular heart disease therapies that are still in the clinical trial phase. While still investigational, these therapies may address unmet clinical needs and provide potentially lifesaving treatments to patients who otherwise may have only high-risk options or no options at all. Often, hospitals that participate in clinical trials for novel therapies will have early access to the procedure when it becomes commercially available.22 Despite the various benefits to hospitals and patients of participating in clinical trials, inequities in clinical trials persist.
Historically, efforts to improve equity in clinical trials have focused on the sociocultural dynamics among patients, physicians, and communities. Setting racially stratified recruitment targets prior to recruitment was associated with greater diversity among recruited participants.23 A similar community-focused approach was found to be largely successful in a hypertension trial that recruited and randomized Black male participants via Black barbershops in the Los Angeles metro area.24 Comparably fewer efforts have focused on changes in the selection of sites based on patient populations to improve equity in access to novel technologies in trials. Typically, site-selection practices favor the same large sites that routinely conduct trials to meet recruitment goals and project timelines. However, these sites generally do not serve disadvantaged populations and fail to adequately engage community-based clinicians, who serve as key liaisons in connecting low-income, racial and ethnic minority patient populations with clinical trials.25 Moreover, while many clinical trial sites are within short driving distances for patients living in densely populated areas, some clinical trial sites are not and remain largely inaccessible to patients living in rural areas. Thus, there may be disparities in access to trial participation even among established clinical trial sites.
We found that hospitals with the capability to participate in clinical trials for novel transcatheter mitral and tricuspid valve therapies, but did not, took care of a more socioeconomically disadvantaged patient population compared with hospitals that did participate in trials. Patients at hospitals that did participate in clinical trials had a median household income that was $5000 higher than that for patients treated in candidate hospitals that did not participate in trials. They also were from areas with less community distress. Though on unadjusted analyses there were fewer patients in trial hospitals who were dual eligible for Medicaid services, this was not statistically significant in multivariable analysis after adjusting for race and ethnicity.
To participate in clinical trials, hospitals need to have considerable investment in necessary infrastructure, including institutional review boards, clinical research coordinators, physicians with the interest and training to serve as principal investigators, and attorneys to handle an often complicated contracting process. These barriers are exacerbated by low enrollment rates in clinical trials (<1 patient per site per month in some trials) due to narrow inclusion criteria, substantial participant burden, and contracting practices that pay sites per patient enrolled.26,27 Though larger hospitals with robust clinical research operations can break even (or make money) under this system using economies of scale, start-up costs may be prohibitive for hospitals that care for poorer patients and may have smaller revenue margins. Efforts to increase participation of sites caring for socioeconomically disadvantaged patients should focus on reducing participant burden to increase enrollment rates and on reducing the site-level financial and administrative burdens required for clinical trial participation. Alternatively, companies sponsoring clinical trials could be incentivized to include sites caring for more socioeconomically disadvantaged patients.
In contrast, we found that the proportion of Black and Hispanic patients undergoing cardiac surgery or TAVR at trial hospitals was similar to the proportion at nontrial hospitals. Differences were less than 1% and were either not different or significantly greater at trial hospitals adjusting for each marker of socioeconomic status. However, the proportion of patients undergoing cardiac surgery or TAVR who were Black or Hispanic were lower than the overall Medicare population at studied hospitals. Given the well-documented racial and ethnic inequities in trial enrollment, these data would suggest that inequities in trial enrollment of Black and Hispanic patients are not caused by the selection of sites with few racial and ethnic minority patients, but instead are due to issues with enrollment among existing sites.8,9
Black and Hispanic patients may face structural barriers limiting their enrollment in trials. In particular, the health care system has failed to earn and maintain trust from minoritized racial and ethnic groups due to historical mistreatment in scientific research and clinical care, as well as structural racism and implicit biases among treating clinicians.28,29,30,31,32,33 It is also possible that racial and ethnic enrollment disparities in mitral and tricuspid valve therapy trials may, in part, stem from upstream disparities in referrals to structural heart programs and diagnosis of underlying valvular heart disease. Rather than trying to recruit sites that care for more racial and ethnic minority groups, efforts to improve the representation of Black and Hispanic patients could focus on enriching the enrollment of these patients at existing sites. Specifically, increasing diversity among clinical trial leadership, liaising partnerships between site-level principal investigators and community stakeholders, and addressing unconscious biases in all stages trial recruitment and enrollment may be potentially effective strategies to increase representation of minoritized racial and ethnic groups.34,35,36,37
Limitations
There are several limitations to this study. First, the use of administrative claims data precludes us from the granularity necessary to identify eligible patients at each of these hospitals for the studied trials with severe mitral or tricuspid valve disease meeting trial eligibility criteria. Instead, we used the population of patients undergoing cardiac surgery or TAVR, which we felt would be reflective of the pool of patients potentially eligible for trial participation for percutaneous valve therapy. We included patients who underwent their operation in 2019, which we felt would be representative of the patients undergoing cardiac surgery and TAVR at these hospitals. Second, we limited our analysis to transcatheter mitral and tricuspid valve therapies. This represents just one area of technological advancement in medicine. These results may not be generalizable to other clinical trials for other conditions. Third, we limited our analysis to fee-for-service beneficiaries and did not have access to Medicare Advantage beneficiaries. However, taken together, this represents a unique analysis of the basis of inequities in clinical trials for transcatheter therapies for mitral and tricuspid valve disease, and clinical trials overall.
Conclusions
In this cohort study among candidate hospitals for clinical trials for transcatheter mitral or tricuspid valve therapies, trial hospitals took care of more socioeconomically advantaged patients and similar numbers of Black and Hispanic patients compared with nontrial hospitals. These data suggest that site selection efforts may improve enrollment of socioeconomically disadvantaged patients but may not improve the enrollment of Black and Hispanic patients.
eFigure: CONSORT Diagram of Hospitals Included in the Study
eTable 1: Transcatheter Mitral and Tricuspid Valve Therapy Clinical Trials Included in Study Cohort
eTable 2: Mitral and Tricuspid Valve Procedures Performed at Non-Trial and Trial Hospitals in 2019 Among Medicare Fee-for-Service Beneficiaries Aged 66 Years and Older
eTable 3: Differences in Racial, Ethnic and Socioeconomic Status Among All Medicare Beneficiaries Treated in Trial Versus Non-Trial Hospitals Adjusted for Hospital, Demographic and Clinical Characteristics
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eFigure: CONSORT Diagram of Hospitals Included in the Study
eTable 1: Transcatheter Mitral and Tricuspid Valve Therapy Clinical Trials Included in Study Cohort
eTable 2: Mitral and Tricuspid Valve Procedures Performed at Non-Trial and Trial Hospitals in 2019 Among Medicare Fee-for-Service Beneficiaries Aged 66 Years and Older
eTable 3: Differences in Racial, Ethnic and Socioeconomic Status Among All Medicare Beneficiaries Treated in Trial Versus Non-Trial Hospitals Adjusted for Hospital, Demographic and Clinical Characteristics
