Underrepresentation In Clinical Trials Research Articles

Barriers to Accessing and Engaging in HIV Preventive Care and Pre-Exposure Prophylaxis Experienced by Transgender Women in Florida.

PrEP, a biomedical HIV prevention option, continues to be underutilized among transgender women who could benefit from sustained use, especially women of color and those who identify as Latina and/or reside in the southeastern US. We explored the barriers and facilitators experienced by transgender women who live in Florida regarding accessing, using, and/or staying on PrEP. In-depth interviews and focus groups were conducted in either Spanish or English with adult transgender women living in Florida (N = 22). The interviews were audio-recorded, transcribed, and coded in ATLAS.ti using thematic analyses. The mean age of the participants was 42.2 years. Among the participants, 73% were Hispanic/Latina, 59% were foreign-born, and approximately one-third were living with HIV (but had past experience with PrEP). Transgender women cited the following barriers to accessing or considering PrEP: (1) costs and benefits of PrEP use; (2) under-representation in clinical trials resulting in unknown or misinformation regarding PrEP side effects; (3) chronic poverty; and (4) trauma and discrimination. Other stressors, such as behavioral healthcare needs, were identified. Our analysis revealed interlocking systems of oppression like transphobia, discrimination, and misgendering, which were common barriers experienced by our participants. These synergistically epidemic (i.e., syndemic) barriers contributed to their feelings of being systematically excluded in social spaces, research, public health planning and policies, laws, and social programs related to PrEP. These structural barriers are impediments to HIV preventive care but also act as a source of stress that contributes to mental health problems, financial vulnerability, substance abuse, and other deleterious health outcomes.

LOWER MORTALITY RISK WITH COMBINATION THERAPY WITH ANTI-TNF THERAPY AND THRIOPURINE COMPARED TO THIOPURINE ALONE IN ELDERLY PATIENTS WITH UC

Abstract INTRODUCTION Despite increasing incidence rates of ulcerative colitis (UC) in the elderly, efficacy and safety data for medical management in this cohort is lacking due to underrepresentation in clinical trials and registries. Selection of medical therapy is often complex, taking into consideration a multitude of factors, including real and perceived risks of infection and malignancy. In the past, immunomodulators, such as thiopurines, were commonly used as monotherapy for maintenance, offering the added advantages of affordability and oral administration. Indeed, there are elderly patients who have been maintained for decades on thiopurine monotherapy. Further, thiopurines can be used in combination with anti-TNF therapy for improved efficacy and reduced immunogenicity compared to monotherapy with either agent in ulcerative colitis (UC). Whether the use of combination therapy imposes an additive risk compared to thiopurine monotherapy is still unclear. This study aimed to investigate outcomes of thiopurine monotherapy versus combination therapy with anti-TNF agents in elderly patients (age ≥65 years) with UC. METHODS The TriNetX Research Network was accessed on October 15th, 2023, to compare outcomes in elderly patients 65 years or older with UC who are receiving thiopurine monotherapy and patients who are receiving combination therapy with an anti-TNF (adalimumab, certolizumab pegol, golimumab, or infliximab). The outcomes examined were 1-year rate of corticosteroid and colectomy as well as 10-year rate of mortality, colon cancer, skin cancer, and respiratory and urinary tract infections. Statistical risk analysis was performed using the TriNetX analytical platform. RESULTS A total of 2,597 patients (2,245 thiopurines monotherapy and 352 AZA plus anti-TNF combination therapy) were included in the study (Table 1). Among the monotherapy and combination therapy cohorts, mean age was 71 years old and approximately 56% male. Ten-year mortality was higher in the thiopurine monotherapy group (OR 1.67, p=0.002). The combination therapy cohort had higher rates of steroid use (32.4% vs. 24.3%, p=0.001) and colectomy at 1 year compared to the monotherapy cohort (4.5% vs. 1.2%, p<0.001). There was no significant difference in 10-year risk of colon cancer (OR 1.05, p=0.88), skin cancer (OR 1.51, p=0.06), incidence of respiratory (OR 1.48, p=0.07) and urinary tract infections (OR 1.18, p=0.23). CONCLUSION The study findings highlight the risks of thiopurine use in patients over the age of 65 given the significantly higher 10-year mortality risk in thiopurine monotherapy-treated patients. The results also suggest that combination therapy with thiopurine and anti-TNF therapies - despite utilization in patients with more active disease indicators - is not associated with an additive risk in terms of infection and mortality in elderly patients. Table 1 Characteristics and Outcomes of Elderly Patients with UC either on Thiopurine Monotherapy or Combination Therapy with anti-TNF agents

Immunotherapy in Elderly Patients-Single-Center Experience.

Cancer management faces a substantial challenge posed by the aging demographic. Aging is marked by accumulated DNA damage, and this phenomenon is implicated in the process of tumorigenesis. The concept of immunosenescence, postulated to manifest in elderly individuals, is defined by an age-related decline in T cells and a simultaneous elevation in proinflammatory status, leading to a diminished efficacy in response to immunotherapy. Notably, despite the rising prevalence of cancer in the elderly population, their underrepresentation in clinical trials persists. This underscores the unmet need to evaluate the safety and efficacy of cancer treatment in the elderly. This retrospective, single-center cohort study aimed to assess and evaluate the effectiveness and safety of immunotherapy in patients compared to younger individuals with metastatic solid tumors receiving ICI. A total of 220 patients were included, mostly males, with a median age of 64. The proportion of patients ≥ 65 years old was 56.5%. The use of ICI showed no significant differences concerning overall survival (OS) and progression-free survival (PFS) among age groups across different cancer types (melanoma, non-small-cell lung cancer (NSCLC), renal, and bladder cancer; p = 0.388). Concerning the response to treatment in renal cancer patients, a significant difference was observed (p = 0.041), suggesting a potential negative impact of age on the treatment response. In patients that presented immune-related adverse events (irAEs), oral corticosteroid therapy was marginally associated (p = 0.059) with the elderly population. When evaluating the NSCLC population alone (n = 131, 59.5%), our study revealed a strong association between the development of irAEs, patients' PFS and OS, and the duration of ICI treatment, but not directly correlated with age. The NSCLC elderly population presented a marginally greater number of irAEs, although without statistical significance (p = 0.86). ICI maintained efficacy and safety in elderly patients, challenging the notion that age alone should determine treatment decisions. The findings emphasize the necessity of a comprehensive geriatric assessment rather than relying solely on chronological age for personalized cancer treatment in the elderly population. Further prospective studies are needed to better understand immune responses in older adults and derive predictive biomarkers for cancer treatment.

Abstract A119: Unveiling disparities in clinical trial participation: Exploring socioeconomic barriers and access to insurance among diverse ethnic groups

Abstract Introduction: Diversity in clinical trials (CTs) is crucial for enhancing the ability to generalize research findings and promote equal health services for underserved populations. Researchers and companies seeking approval for late-stage CTs are now asked by the US Food and Drug Administration (FDA) to provide a diversity plan to ensure inclusivity among CT participants. To design such a plan, it is important to study the barriers leading to underrepresentation in CTs. While CTs interventions are mostly covered by trial sponsors, insurance coverage is still required for participation. We studied the impact of insurance coverage, as a potential  factor impacting participation in CTs among underserved communities, while considering other key parameters such as age, sex, cancer type and disease status. Methods: Leal is an AI-based platform that matches cancer patients (pts) to CTs based on a self reported medical profile. The profile includes parameters essential for CT matching including disease status, stage, biomarker/mutational status, treatment history, comorbidities and demographics. This study included a multi-ethnic cohort of 4,525 pts who signed up to the platform in 2023. We analyzed potential barriers for CT enrollment among various ethnic groups. We implemented the non-parametric Pearson's Χ², the Welch's t-test and the Games-Howell pairwise comparisons tests, at significance level of 0.05. Results: Insurance coverage was significantly linked to ethnicity. Non-white pts comprised 37% of uninsured pts, which was markedly higher compared to their representation in the insured group (24%, p<0.0001). Medicaid had the most diverse subscriber base (33%) compared to other insurance providers (p<0.0001), independently from disease status and cancer type. In addition, when considering participation in CTs, 78% of non-white pts were willing to travel up to 50 miles, while a larger percentage of white pts (64%) were open to traveling between 100 and 200 miles (p<0.0001). Conclusions: We found a strong association between socioeconomic status and potential barriers for CTs participation including insurance coverage and willingness to travel. The higher proportion of uninsured non-whites highlights the disparity in access to insurance of underserved populations. This may stem from both financial constraints or limited education and community resources. Medicaid had the most diverse subscriber base, which is aligned with its aim to provide coverage to pts with low income. To increase diversity in CTs, financial support programs for uninsured patients should be considered. In addition, CT sites should consider incorporating insurance programs for pts with disadvantaged backgrounds. Our study also revealed reduced willingness among non-whites to travel long distances to trial sites. To ensuring representative outcomes across diverse populations, regardless of location or socioeconomic status, requires addressing accessibility limitations through financial support, localized trial sites, and community-targeted recruitment strategies. Citation Format: Ritta Jubran, Yelena Lapidot, Tzvia Bader, Avital Gaziel. Unveiling disparities in clinical trial participation: Exploring socioeconomic barriers and access to insurance among diverse ethnic groups [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A119.

Survival Outcomes and Health-Related Quality of Life in Older Adults Diagnosed with Acute Myeloid Leukemia Receiving Frontline Therapy in Daily Practice.

Acute myeloid leukemia has a poor prognosis in older adults, and its management is often unclear due to its underrepresentation in clinical trials. Both overall survival (OS) and health-related quality-of-life (HRQoL) are key outcomes in this population, and patient-reported outcomes may contribute to patient stratification and treatment assignment. This prospective study included 138 consecutive patients treated in daily practice with the currently available non-targeted therapies (intensive chemotherapy [IC], attenuated chemotherapy [AC], hypomethylating agents [HMA], or palliative care [PC]). We evaluated patients' condition at diagnosis (Life expectancy [Lee Index for Older Adults], Geriatric Assessment in Hematology [GAH scale], HRQoL [EQ-5D-5L questionnaire], and fatigue [fatigue items of the QLQ-C30 scale]), OS, early death (ED), treatment tolerability (TT) and change in HRQoL over 12 months follow-up. The median OS was 7.1 months (IC not reached, AC 5.9, HMA 8.8, and PC 1.0). Poor risk AML category and receiving just palliative care, as well as a higher Lee index score in the patients receiving active therapy, independently predicted a shorter OS. The Lee Index and GAH scale were not useful for predicting TT. The white blood cell count was a valid predictor for ED. Patients' HRQoL remained stable during follow-up.

Commentary: Some water in the data desert: the Cancer Intervention and Surveillance Modeling Network's capacity to guide mitigation of cancer health disparities.

Despite significant progress in cancer research and treatment, a persistent knowledge gap exists in understanding and addressing cancer care disparities, particularly among populations that are marginalized. This knowledge deficit has led to a "data divide," where certain groups lack adequate representation in cancer-related data, hindering their access to personalized and data-driven cancer care. This divide disproportionately affects marginalized and minoritized communities such as the U.S. Black population. We explore the concept of "data deserts," wherein entire populations, often based on race, ethnicity, gender, disability, or geography, lack comprehensive and high-quality health data. Several factors contribute to data deserts, including underrepresentation in clinical trials, poor data quality, and limited access to digital technologies, particularly in rural and lower-socioeconomic communities.The consequences of data divides and data deserts are far-reaching, impeding equitable access to precision medicine and perpetuating health disparities. To bridge this divide, we highlight the role of the Cancer Intervention and Surveillance Modeling Network (CISNET), which employs population simulation modeling to quantify cancer care disparities, particularly among the U.S. Black population. We emphasize the importance of collecting quality data from various sources to improve model accuracy. CISNET's collaborative approach, utilizing multiple independent models, offers consistent results and identifies gaps in knowledge. It demonstrates the impact of systemic racism on cancer incidence and mortality, paving the way for evidence-based policies and interventions to eliminate health disparities. We suggest the potential use of voting districts/precincts as a unit of aggregation for future CISNET modeling, enabling targeted interventions and informed policy decisions.

Outcomes of male patients with HR+/HER2– advanced breast cancer receiving palbociclib in the real-world POLARIS study

PurposeData on treatments for male breast cancer patients are limited owing to rarity and underrepresentation in clinical trials. The real-world POLARIS study gathers data on palbociclib use for the treatment of hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) advanced breast cancer (ABC) in female and male patients. This sub-analysis describes real-world palbociclib treatment patterns, clinical outcomes, and quality of life (QoL) in male patients.MethodsPOLARIS is a prospective, noninterventional, multicenter, real-world study of patients with HR+/HER2– ABC receiving palbociclib. Assessments included medical record reviews, patient QoL questionnaires (European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire–Core 30), site characteristics questionnaires, and physician treatment selection surveys. Variables included demographics, disease history, global health status/QoL, clinical assessments and adverse events. Analyses were descriptive in nature. For clinical outcomes, real-world tumor responses and progression were determined by physician assessment in routine clinical practice. Real-world progression-free survival (rwPFS) was described using the Kaplan–Meier method.ResultsAt data cutoff, 15 male patients were enrolled (median age, 66 years). Nine patients received palbociclib as a first-line treatment and 6 as a second-line or later treatment. Patients received a median of 20 cycles of palbociclib. Neutropenia was experienced by 2 patients and grade ≥ 3 adverse events were reported in 11 patients. Global health status/QoL scores remained generally consistent during the study. One patient (6.7%) achieved a complete tumor response, 4 (26.7%) a partial response, and 8 (53.3%) stable disease. Median rwPFS was 19.8 months (95% CI, 7.4–38.0). Median follow-up duration was 24.7 months (95% CI, 20.0–35.7).ConclusionThis real-world analysis showed that palbociclib was well tolerated and provides preliminary data on treatment patterns and outcomes with palbociclib in male patients with HR+/HER2– ABC, helping inform the use of palbociclib in this patient subgroup.Trial identifierNCT03280303.

The Real-Life Impact of mFOLFIRI-Based Chemotherapies on Elderly Patients-Should We Let It or Leave It?

The oncologic treatment of elderly patients is going on with a lack of evidence due to their underrepresentation in clinical trials. Many data suggest that certain groups of elderly patients, like their younger counterparts, may benefit from the systemic treatment of their metastatic colorectal tumors (mCRC). We performed retrospective data analysis to investigate the clinical course of care and clinical outcomes of 515 patients who received first-line mFOLFIRI-based chemotherapy for mCRC between 1 January 2013 and 31 December 2018 at the Institute of Oncotherapy of the University of Pécs, focusing on a comparison of patients over and under 70 years of age, defined as the cut-off value. 28.7% of the 515 patients were 70 years old and older (median age 73.5 years). Compared to the data of the elderly patients, the younger group (median age 61.1 years) had a performance status that was significantly better (average ECOG 1.07 vs. 0.83, p < 0.0001), and significantly more patients received molecularly targeted agents (MTA) (21.6% vs. 51.8%, p < 0.0001); nevertheless, mPFS (241 vs. 285 days, p = 0.3960) and mOS (610 vs. 698 days, p = 0.6305) results did not differ significantly. Considering the 1y PFS OR and the 2ys OS OR values (0.94 [95%CI 0.63-1.41] and 0.72 [95%CI 0.47-1.09], respectively), only a non-significant trend was observed in OS favouring the younger population. Additional analysis of our data proved that the survival in patients over 70 years was positively affected by the addition of MTAs to the doublet chemotherapies, and the reasonable modifications/reductions in dose intensity and the addition of local interventions had similar positive effects as observed in the younger patients' group. Age stratification of mCRC patients is not professionally justified. Patients over 70 years of age with good performance status and controlled co-morbidities benefit from systemic therapy, its modifications and local treatment to the same extent as younger patients. With the increasing incidence of age-related cancers due to the rising average lifespan, prospective randomised clinical trials are needed to determine the real value of systemic therapy in the elderly and the rational, objective methods of patient selection.

Prescriptions of newer glucose regulating agents in older hospitalized patients with type 2 diabetes A retrospective cohort study

AimsGLP-1-analogues, DPP4-inhibitors, and SGLT2-inhibitors have become available to treat type 2 diabetes. The extent to which these glucose regulating agents (GRA) are prescribed to older patients is unknown. MethodsWe performed a retrospective observational cohort study including all clinical admissions of patients with one or more prescriptions for non-insulin GRA between 2017 and 2021. We analyzed prescription trends and differences in prescription prevalences for frail and non-frail older patients, as well as older (≥ 70 years) versus younger patients. ResultsIn total 11.5% of admissions had one prescription or more of newer GRA; GLP-1-analogues 1.6%, DPP4-inhibitors 7.3% and SGLT2-inhibitors 2.3%. Total prescription prevalence increased from 8.4% to 16.3% (p < 0.001). Prescription prevalence was 11.1% (N = 129) in admissions of frail patients versus 14.6% (N = 344) of non-frail patients (p = 0.005) and 15.0% in admissions of younger patients versus 11.5% of older patients (p < 0.001). ConclusionsPrescription prevalence of newer GRA in clinical admissions of older patients (≥ 70 years) increased from 2017 to 2021. Prevalence was lower in admissions of frail and older patients, possibly because they are undertreated due to a lack of clear recommendations for older patients in guidelines and underrepresentation in clinical trials.

First-line systemic treatment with palbociclib in women aged ≥70 years presenting with hormone receptor-positive advanced breast cancer: Results from the PALOMAGE program.

1018 Background: Endocrine therapy (ET) combined with a CDK4/6 inhibitor is standard of care for hormone receptors-positive (HR+) advanced breast cancer (ABC). In France, 33% of BC are diagnosed in women aged 70 and older, contrasting with their constant underrepresentation in clinical trials. PALOMAGE, a prospective, observational, longitudinal real-life program, assessed the feasibility of ET combined with palbociclib (PAL), specifically in women aged ≥70 years with HR+ HER2- ABC. Methods: Depending on prior treatment for ABC and time of relapse, women were enrolled in two cohorts: ET-sensitive disease (no prior systemic treatment for ABC and no relapse within 1 year after adjuvant ET, cohort A) or ET-resistant disease (relapse on adjuvant ET or &lt; 1 year after completion, or prior treatment for ABC, cohort B). Data collected at baseline and then every 3 months included: sociodemographic, clinical, biological, disease- and treatment-related, response, quality of life (QoL; EORTC QLQ-C30 and ELD14), geriatric (G8 and Geriatric-COre DatasEt [G-CODE]) and safety. Results of feasibility in cohort B (rate of PAL discontinuation at 6 months 28.8%) were reported at SABCS 2021. Here, we report results in cohort A, based on the rate of PAL discontinuation at 18 months for any reason as the primary endpoint. Secondary endpoints included time-to-treatment failure (TTF), progression-free survival (PFS), QoL, and safety. Results: For this analysis, 362 patients (from 130 sites) with sufficient data were considered: median age was 78 years (range: 70-94), ECOG was ≥2 in 19.2%, and visceral metastases was present in 39.8%. PAL starting dose was 125 mg, 100 mg, and 75 mg in 80.0%, 14.4%, and 5.6% of patients, respectively, and combined with an aromatase inhibitor in 93.6% or fulvestrant in 6.4%. Baseline scores showed G8 ≤14, ADL ≤5 and IADL ≤3 in 68.2%, 15.5% and 29.4% of patients, respectively. Among the 362 patients, 327 were evaluable for the primary endpoint. With a median follow-up of 20.7 months (95% CI: 18.8-22.0), the 18-month discontinuation rate for PAL was 41.9% (95% CI: 36.6%-47.2%), due to disease progression (20.8%), toxicity (7.7%), patient’s choice (6.7%), death (4.6%), or other reason (2.1%). Median TTF and PFS were 22.7 months (95% CI: 19.1–26.0) and 28.1 months (95% CI: 25.6-not reached), respectively. Safety profile showed (360 patients evaluable) 54.4% all grade neutropenia (1.1% febrile neutropenia). Impact of geriatric status on effectiveness and safety will be presented, together with the evolution of QoL. Conclusions: In a large real-life population of older women with G8 impaired in two thirds and with ET-sensitive ABC, discontinuation rate of PAL at 18 months was 41.9%, with a median PFS of 28.1 months, consistent with PALOMA2 results. Optimized ET combined with PAL is feasible in unselected older women with HR+ ET-sensitive ABC.

An evaluation of biobanking and therapeutic clinical trial representation among adult glioma patients from rural and urban Utah.

Social determinants of health (SDOHs)-specifically those related to rurality, health care accessibility, and income-may play as-yet-unidentified roles in prognosis for glioma patients, and their impact on access to clinical trials is important to understand. We examined SDOHs of patients enrolled in glioma clinical trials and evaluate disparities in trial participation and outcomes between rural and urban patients. We retrospectively identified patients enrolled in glioma clinical trials at Huntsman Cancer Institute (HCI) from May 2012 to May 2022 to evaluate clinical trial participation. We used multivariable models to evaluate SDOHs and geographic information system mapping to assess representation across Utah's counties. We utilized the most recent 10-year datasets of patients treated for glioma at HCI and from the Utah Cancer Registry to analyze survival and incidence, respectively. A total of 570 participants (68 trials) resided in Utah, 84.4% from urban counties, 13.5% from rural counties, and 2.1% from frontier (least-populous) counties. Nineteen counties (65.5%) were underrepresented in trials (enrolled participants vs. eligible), 1 (3.5%) was represented in a near-1:1 ratio, and 9 (31.0%) were overrepresented. Counties with greater enrollment had greater population densities, highest per-capita income, and proximity to HCI. Among patients treated at HCI, patients from rural/frontier counties had equivalent survival with urban patients across nearly all glioma types, including glioblastomas, despite underrepresentation in clinical trials. By highlighting disparities in clinical trial enrollment, our results can support efforts to improve recruitment in underrepresented regions, which can assist providers in delivering equitable care for all patients.

Ethnic minority representation in UK COVID-19 trials: systematic review and meta-analysis

BackgroundThe COVID-19 pandemic has highlighted health disparities affecting ethnic minority communities. There is growing concern about the lack of diversity in clinical trials. This study aimed to assess the representation of ethnic groups in UK-based COVID-19 randomised controlled trials (RCTs).MethodsA systematic review and meta-analysis were undertaken. A search strategy was developed for MEDLINE (Ovid) and Google Scholar (1st January 2020–4th May 2022). Prospective COVID-19 RCTs for vaccines or therapeutics that reported UK data separately with a minimum of 50 participants were eligible. Search results were independently screened, and data extracted into proforma. Percentage of ethnic groups at all trial stages was mapped against Office of National Statistics (ONS) statistics. Post hoc DerSimonian-Laird random-effects meta-analysis of percentages and a meta-regression assessing recruitment over time were conducted. Due to the nature of the review question, risk of bias was not assessed. Data analysis was conducted in Stata v17.0. A protocol was registered (PROSPERO CRD42021244185).ResultsIn total, 5319 articles were identified; 30 studies were included, with 118,912 participants. Enrolment to trials was the only stage consistently reported (17 trials). Meta-analysis showed significant heterogeneity across studies, in relation to census-expected proportions at study enrolment. All ethnic groups, apart from Other (1.7% [95% CI 1.1–2.8%] vs ONS 1%) were represented to a lesser extent than ONS statistics, most marked in Black (1% [0.6–1.5%] vs 3.3%) and Asian (5.8% [4.4–7.6%] vs 7.5%) groups, but also apparent in White (84.8% [81.6–87.5%] vs 86%) and Mixed 1.6% [1.2–2.1%] vs 2.2%) groups. Meta-regression showed recruitment of Black participants increased over time (p = 0.009).ConclusionsAsian, Black and Mixed ethnic groups are under-represented or incorrectly classified in UK COVID-19 RCTs. Reporting by ethnicity lacks consistency and transparency. Under-representation in clinical trials occurs at multiple levels and requires complex solutions, which should be considered throughout trial conduct. These findings may not apply outside of the UK setting.

Effect of race-free estimated glomerular filtration rate equations (eGFR) on oncology clinical trial eligibility for Black patients.

611 Background: Race is no longer recommended in estimated glomerular filtration rate (eGFR) equations. The resulting lower eGFR may positively impact black patients, such as with earlier nephrology referral. However, the impact of race-free equations on black oncology patients–a cohort more likely to experience inferior cancer outcomes and underrepresentation in clinical trials–has not been fully examined. Here, we analyze removal of race from eGFR in black patients with cancer, specifically with regards to clinical trial eligibility. Methods: Self-identified black patients undergoing nephrectomy at a referral center from 2009-2021 were identified. Patients with end-stage renal disease were excluded. Using preoperative creatinine, height, and weight, eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation with and without race (CKD-EPI-WithRace; CKD-EPI-WithoutRace, respectively), and the Modification of Diet in Renal Disease equation with and without race (MDRD-WithRace; MDRD-WithoutRace, respectively). Distribution of patients and changes within CKD stages with different equations was considered. Theoretical exclusion at commonly observed clinical trial eGFR points was then simulated based on utilization of the race coefficient. Subgroup analysis was completed on patients with stage III-IV disease only. Results: 459 self-identified black patients that underwent nephrectomy at our institution were identified, 135 of which had stage III-IV disease. On average, eGFR decreased around 10-13ml/min/1.73m2 with removal of the race coefficient (Table). 13-22%, 6-12%, and 2-3% more black patients would fall under common clinical trial cutoffs of 60, 45, or 30ml/min cutoffs, respectively, depending on the equation used (Table). Subanalysis of stage III-IV patients only were similar. Conclusions: Race free renal function equations may inadvertently result in increased exclusion of black patients from clinical trials. [Table: see text]

Community engagement and clinical trial diversity: Navigating barriers and co-designing solutions-A report from the "Health Equity through Diversity" seminar series.

In recent years, there has been increasing awareness of the lack of diversity among clinical trial participants. Equitable representation is key when testing novel therapeutic and non-therapeutic interventions to ensure safety and efficacy across populations. Unfortunately, in the United States (US), racial and ethnic minority populations continue to be underrepresented in clinical trials compared to their White counterparts. Two webinars in a four-part series, titled "Health Equity through Diversity," were held to discuss solutions for advancing health equity through diversifying clinical trials and addressing medical mistrust in communities. Each webinar was 1.5 hours long, beginning with panelist discussions followed by breakout rooms where moderators led discussions related to health equity and scribes recorded each room's conversations. The diverse groups of panelists included community members, civic representatives, clinician-scientists, and biopharmaceutical representatives. Scribe notes from discussions were collected and thematically analyzed to uncover the central themes. The first two webinars were attended by 242 and 205 individuals, respectively. The attendees represented 25 US states, four countries outside the US, and shared various backgrounds including community members, clinician/researchers, government organizations, biotechnology/biopharmaceutical professionals, and others. Barriers to clinical trial participation are broadly grouped into the themes of access, awareness, discrimination and racism, and workforce diversity. Participants noted that innovative, community-engaged, co-designed solutions are essential. Despite racial and ethnic minority groups making up nearly half of the US population, underrepresentation in clinical trials remains a critical challenge. The community engaged co-developed solutions detailed in this report to address access, awareness, discrimination and racism, and workforce diversity are critical to advancing clinical trial diversity.

Underrepresentation of ethnic and regional minorities in lipid-lowering randomized clinical trials: a systematic review and meta-analysis.

The efficacy of lipid-lowering therapies (LLT) among different ethnicities and regions remains unclear. We aimed to assess cardiovascular event reductions associated with LLT according to ethnicity and region in previously published randomized clinical trials (RCTs). Medline, EMBASE and Cochrane CENTRAL were searched for RCTs of statins, ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors comparing intensive versus less intensive low-density lipoprotein cholesterol (LDL-C) lowering. The primary endpoint was major adverse cardiovascular events (MACE) defined as the composite of cardiovascular mortality, myocardial infarction, stroke and revascularisation. Random effects meta-analysis was used to pool risk ratios (RR) with 95% confidence intervals (CI) adjusted per mmol/L reduction in LDL-C. Fifty-three trials with 329,897 participants were included. Among participants, 39.5% were from Europe, 16.0% from North America, 9.0% from Japan, 2.8% from Australasia, 1.8% from South America, 1.1% from Asia, 0.6% from South Africa and 29.2% were unspecified. Among trials reporting ethnicities, there were 60.3% White, 20.2% Japanese, 9.4% Asian, 5.5% Black and 4.7% Latin American. There was reduction in MACE with LLT in regions including Australasia (RR 0.75, 95% CI 0.67-0.85), North America (RR 0.75, 95% CI 0.69-0.83), Europe (RR 0.78, 95% CI 0.71-0.86) and Japan (RR 0.73, 95% CI 0.63-0.85), and in Black ethnicity (RR 0.55, 95% CI 0.37-0.82). Head-to-head comparisons between regions and ethnicities revealed no significant differences in MACE reduction. Despite underrepresentation in clinical trials, regional and ethnic minority groups such as Australasia and Blacks appear to derive at least as much cardiovascular benefit from LLT.

P466 Efficacy and safety outcomes in patients with moderate to severe ulcerative colitis stratified by ethnicity and race: a pooled analysis of data from GEMINI 1, VARSITY, and VISIBLE 1

Abstract Background Ulcerative colitis (UC) is an inflammatory bowel disease with an estimated prevalence of 181 cases per 100,000 adults in the USA. Hispanic or Latino individuals comprise 19% of the US population and 24% of individuals are races other than White; however, the efficacy and safety of advanced therapies for UC in these populations remains uncertain because of their underrepresentation in clinical trials. Underrepresentation has the potential to bias evidence towards therapies with understudied efficacy and safety in minority ethnic and racial groups. This post hoc analysis used pooled clinical trial data of advanced therapies in patients with UC stratified by ethnicity and race in order to identify differential efficacy and safety outcomes among the populations investigated. Methods GEMINI 1, VARSITY, and VISIBLE 1 were phase 3 or 3b clinical trials investigating vedolizumab (intravenous or subcutaneous) versus placebo or adalimumab in patients with moderately to severely active UC. Data from these trials were pooled to create three cohorts of patients who received adalimumab, vedolizumab, or placebo. The number and proportion of patients with each efficacy and safety outcome at week 52 were reported for each of the treatment cohorts, stratified by ethnicity and race. Ethnicity and race were self-reported in the three trials. Results Overall, 1,358 patients were included in the pooled treatment cohorts. Of the 465 patients with available ethnicity information, only 40 patients (8.6%) reported their ethnicity as Hispanic or Latino. Efficacy and safety outcomes were similar when stratified by ethnicity with some exceptions (Table 1). When stratified by race, efficacy and safety outcomes were similar among White and Asian patients (Table 2). In the vedolizumab cohort, 47.3% and 47.1% of White and Asian patients, respectively, had mucosal healing. Some differences were observed in the efficacy and safety outcomes of Black patients compared with White and Asian patients; however, the treatment cohorts included fewer than 10 Black patients. Conclusion In the GEMINI 1, VARSITY, and VISIBLE 1 trials, efficacy and safety outcomes were similar among racial and ethnic groups, with the exception of Black patients. However, this analysis was limited by the small sample size of patients of races other than White, as well as the limited availability of ethnicity information, which prevented robust comparisons of outcomes between patients of different ethnicities and races. Future clinical trials of advanced therapies should aim to recruit and report a diverse patient population with UC who are representative of the patients who will receive these treatments.

967 THIRD GENERATION, ULTRATHIN STRUTS STENT IN WOMEN COMPARED TO MEN: A GENDER-RELATED ANALYSIS

Abstract Introduction Female patients underrepresentation in clinical trials is a well known issue in clinical research, especially harming the assessment of interventional cardiovascular devices. Limited inclusion of women in such studies might lead to suboptimal care, as results derived from predominantly male populations might not hold true for female patients. In recent years, third generation drug-eluting stents have become the standard of care for percutaneous coronary interventions (PCI). Among them, the Orsiro sirolimus-eluting stent carries some promising features such some of the thinnest struts among commercially available devices (60-80 µm), a bioresorbable-polymer and an amorphous silicon carbide coating. We performed the presents study with the aim to assess if use of this stent in a real-world setting might lead to differential clinical outcomes in women compared to men. Methods This is a retrospective study conducted at a single, high-volume center, including all patients undergoing PCI with the implantation of at least one Orsiro for acute or chronic coronary syndromes between January 2017 and December 2019. Main clinical and procedural features were collected, as well as in hospital outcomes. Follow-up data were collected by outpatient visit or by telephone interview. Target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction or target lesion revascularization, was the main outcome. Results Out of a total of 416 patients treated with at least an Orsiro stent, 66 (15.9%) were women and 349 (84.1%) men. No significant differences were observed at baseline, excepted for a higher age (median age 70 vs. 66, P=0.003) and a lower BMI (25.0 vs. 26.1, P=0.010) in women compared to men. No gender-related differences were observed in the indication for PCI, with most of the patients presenting with chronic coronary syndrome (329, 79.3%), rather than acute coronary syndrome in (86, 20.7%). The global number of treated lesions was 558 (90 in women, 468 in men); frequency of left main (5.3% vs. 3.0%) and left anterior descending (34.9% vs. 42.4%) PCI was similar (P=0.28). Treated vessels number of treated lesion per patients (1.36 vs. 1.34, P=0.83), cumulative stent length (33.6 mm vs. 38.4, P=0.078) and mean stent diameter (2.92 vs. 3.0 mm, P=0.39) was not different between men and women. Technical and clinical success was achieved in all cases. Two cases (0.5%) of stent thrombosis, one early and one late, were documented, all in men. After a median follow-up of 402 days, the main outcome of TLF was observed in 10 (2.9%) men and 2 (3.0%) women, with no significant differences at log-rank analysis (2.34 events per 100 patient-years in males, 2.53 in females; P=0.80). In the subgroup of patients undergoing small-vessel PCI (stent diameter ≤ 2.5 mm) no differences were observed in terms of TLF at follow-up between women and men (3.2% vs. 4.9%; P = 0.68). Similar findings emerged in the subgroup of patients presenting with acute coronary syndrome (6.3% vs. 4.3%, P = 0.74) Conclusions Ultrathin struts Orsiro stent did not show significant differences in terms of procedural, short-term and long-term outcomes in women compared to men in a real-world setting. This device may represent a viable option for female and male patients undergoing PCI.

Can we predict trial failure among older adult-specific clinical trials using trial-level factors?

IntroductionConducting older adult-specific clinical trials can help overcome the lack of clinical evidence for older adults due to their underrepresentation in clinical trials. Understanding factors contributing to the successful completion of such trials can help trial sponsors and researchers prioritize studies and optimize study design. We aimed to develop a model that predicts trial failure among older adult-specific cancer clinical trials using trial-level factors. Materials and methodsWe identified phase 2–4 interventional cancer clinical trials that ended between 2008 and 2019 and had the minimum age limit of 60 years old or older using Aggregate Analysis of ClinicalTrials.gov data. We defined trial failure as closed early for reasons other than interim results or toxicity or completed with a sample of <85% of the targeted size. Candidate trial-level predictors were identified from a literature review. We evaluated eight types of machine learning algorithms to find the best model. Model fitting and testing were performed using 5-fold nested cross-validation. We evaluated the model performance using the area under receiver operating characteristic curve (AUROC). ResultsOf 209 older adult-specific clinical trials, 87 were failed trials per the definition of trial failure. The model with the highest AUROC in the validation set was the least absolute shrinkage and selection operator (AUROC in the test set = 0.70; 95% confidence interval [CI]: 0.53, 0.86). Trial-level factors included in the best model were the study sponsor, the number of participating centers, the number of modalities, the level of restriction on performance score, study location, the number of arms, life expectancy restriction, and the number of target size. Among these factors, the number of centers (odds ratio [OR] = 0.83, 95% CI: 0.71, 0.94), study being in non-US only vs. US only (OR = 0.32, 95% CI: 0.12, 0.82), and life expectancy restriction (OR = 2.17, 95% CI: 1.04, 4.73) were significantly associated with the trial failure. DiscussionWe identified trial-level factors predictive of trial failure among older adult-specific clinical trials and developed a prediction model that can help estimate the risk of failure before a study is conducted. The study findings could aid in the design and prioritization of future older adult-specific clinical trials.

SA12 Can We Predicting Trial Failure Among Older Adult-Specific Clinical Trials Using Trial-Level Factors?

Conducting older adult-specific clinical trials can help overcome the lack of clinical evidence for older adults due to their underrepresentation in clinical trials. These trials can help examine potential treatment heterogeneity between older versus younger patients, however there is a risk of failure that trial sponsors should take into account before making funding decisions. We aimed to develop a machine learning model that predicts trial failure among older adult-specific clinical trials using trial-level factors.

Global Investigative Site Personnel Diversity and Its Relationship with Study Participant Diversity.

Background There is little to no empirical data on the race and ethnicity of the global community of professionals conducting clinical trials funded by pharmaceutical and biotechnology companies and little empirical evidence on the relationship between the race and ethnicity of investigative site personnel and the overall and corresponding diversity of participants enrolled.MethodsA global online survey conducted in mid-2021 gathered responses from 3462 clinical research professionals representing approximately 3300 distinct investigative sites.ResultsWorldwide, including all research settings, the majority (64%) of investigative site personnel are White, 20% are LatinX, 6% are Black, 7% are Asian and 3% are other races and ethnicities (e.g., indigenous peoples, Pacific Islander, Middle Eastern, etc.). The representation of non-white site personnel is significantly higher in North America and Rest of World (ROW) compared to Europe. The highest levels of personnel diversity are found in private community-based practices, investigative sites and site networks. A significant correlation (p < 0.001) was found between site personnel diversity and patient enrollment diversity worldwide. As the mix of site personnel by race and ethnicity increases, the diversity of patients enrolled—except for Asian patients in sites outside of North America—also increases. A significant relationship was also found between the proportion of a given race or ethnicity of investigative site personnel and the corresponding race and ethnicity of patients enrolled.ConclusionsAn opportunity exists to address under-representation in clinical trials through identifying, hiring and supporting investigative site personnel to best reflect the patient communities that they serve.