Representation In Clinical Trials Research Articles

Outcomes Among Racial and Ethnic Minority Patients With Advanced Cancers in Phase 1 Trials

Patients from racial and ethnic minority groups (eg, Asian, Hispanic, and non-Hispanic Black patients) have low representation in clinical trials, especially in phase 1 trials in cancer. These trials represent valuable options for patients with advanced cancer who experience disease progression with standard therapy. To determine whether the benefit of enrollment to phase 1 cancer trials extends to Asian, Hispanic, and non-Hispanic Black patients as much as it does for non-Hispanic White patients. Patient records at a single institution from January 1999 to December 2016 were reviewed. Treatment-related responses, toxic effects, and deaths were recorded. All phase 1 studies were included. Data underwent independent extraction by multiple observers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The primary outcome was overall survival (OS), assessed using univariate and multivariable time-to-event analyses. A total of 738 patients (median [range], 60 [22-93] years; 467 [63.3] female) including 197 Hispanic patients (26.7%), 238 non-Hispanic Black patients (32.2%), and 282 non-Hispanic White patients (38.2%), were enrolled in 64 phase 1 trials, including 33 cytotoxic trials (51.5%), 21 biologic trials (32.8%), and 10 combined therapy trials (15.6%). The primary cancer diagnoses were colorectal (187 patients [25.3%]), ovarian (141 patients [19.1%]), lung (58 patients [7.9%]), uterine (49 patients [6.6%]), and breast (41 patients [5.6%]). Patients underwent a median (range) of 3 (0-13) therapies prior to trial enrollment. Among 558 patients evaluated for response, the clinical benefit rate (ie, stable disease plus response rates) was 49.1%, and the overall response rate was 6.5%. Grade 3 or 4 nonhematological toxic effects were observed in 27.8% (95% CI, 24.6%-31.3%) of patients and grade 3 or 4 hematological toxic effects were observed in 19.7% (95% CI, 17.0%-22.8%) of patients. The treatment-related mortality rate was 0.9% (95% CI, 0.4%-1.9%). Median OS was 9.6 (95% CI, 8.2-11.0) months among Hispanic patients, 8.3 (95% CI, 6.7-10.4) months among non-Hispanic Black patients, and 9.8 (95% CI, 8.5-11.4) months among non-Hispanic White patients (P = .13). In a multivariable analysis, age older than 60 years, Eastern Cooperative Oncology Group performance status score of 2 or greater, more than 2 metastatic sites, lactate dehydrogenase grade 1 or 2, grade 2 or greater low albumin, grade 1 or greater total bilirubin, and grade 2 or greater anemia were associated with worse prognosis, whereas leukocytosis greater than grade 1 was associated with better OS. In this meta-analysis assessing outcomes in phase 1 cancer trials among patients from racial and ethnic minority groups, Hispanic and non-Hispanic Black patients had benefits similar to those of non-Hispanic White patients.

Inequities in atrial fibrillation trials: An analysis of participant race, ethnicity, and sex over time

BackgroundDespite the importance of racial and ethnic representation in clinical trials, limited data exist regarding the enrollment trends of these groups in atrial fibrillation (AF) trials over time. ObjectivesThe purpose of this study is to examine the characteristics of contemporary AF clinical trials and evaluate their association with race and ethnicity over time. MethodsWe performed a systematic search of all completed AF trials registered in ClinicalTrials.gov between conception to December 31, 2023 and manually extracted composition of race/ethnicity. We stratified trials by study characteristics, including impact factor, publication status, funding source, and location. We calculated the participation prevalence ratio (PPR) by dividing the percentage of non-White participants by the percentage of non-White participants among the disease population (PPR 0.8-1.2 suggests proportional representation) over time. ResultsWe identified 277 completed AF trials encompassing a total of 1,933,441 adults, with a median proportion of non-White at 12% (IQR: 6-27), 121 (43.7%) device-focused, and 184 (66.4%) funded by industry. Only 36.1% of trials reported comprehensive race information. Overall, non-White participants were underrepresented (PPR = 0.511; P < 0.001), including Black (PPR = 0.263) and Hispanic (PPR = 0.337) participants. The proportion of non-White participants did not change significantly between 2000 and 2023 (11% vs 9%; P = 0.343). ConclusionDespite greater awareness, race/ethnicity reporting and representation of non-White groups in AF clinical trials are poor and have not improved significantly over time. These findings demand additional recruitment efforts and novel recruitment policies to ensure adequate representation of these demographic subgroups in future AF clinical trials.

Enrollment of older adults in clinical trials for oncology indications, 2010-2020: An evaluation by the FDA.

e23029 Background: Underrepresentation of older adults (≥65 years) in clinical trials may limit important evidence for regulatory and clinical decision-making. Prior FDA analysis1 demonstrated underrepresentation of older adults in oncology clinical trials. With recent efforts to encourage inclusion of older adults, we evaluated representation in clinical trials using updated data. Methods: This analysis used patient-level data from pivotal trials supporting approvals of new drugs and biologics, and expanded indications from 2010-2020 for cancers with high incidence in the U.S. population and older adults: breast (BC), colorectal (CRC), non-small cell lung (NSCLC), prostate (PC), chronic myeloid leukemia (CML), and multiple myeloma (MM). Age distribution of trial participants compared to incident cases from the NCI SEER Program was analyzed using the Enrollment to Incidence Ratio (EIR). For each cancer-age group, EIR is the percentage of trial participants divided by percentage of incident cases. Previously established EIR categories of &lt; 0.8, 0.80-1.20, and &gt; 1.2 indicate under-, adequate, and over-representation, respectively. Results: The analysis included 86000 participants in 152 trials. Adults &gt;65 yrs were underrepresented in BC trials. Adults &gt;75 yrs were underrepresented in BC, CRC, NSCLC, CML, and MM trials (Table 1). Conclusions: Despite slight variation across cancers, adults &gt;75 yrs appeared to be underrepresented in clinical trials, excepting PC. Given heterogeneity in the natural history by cancer site, incidence may not best represent age distribution of the intended use population for all trials. Further evaluation using prevalence as a comparator may provide additional insights. Additionally, results may be affected by clinical factors such as stage; however, comparison is limited by SEER data element availability. Planned sensitivity analyses such as stratification by drug class and line of therapy may further elucidate enrollment patterns.

Disparities in gynecologic oncology clinical trial availability in the United States: A state-level analysis.

e23128 Background: Disparities in minority participation in gynecologic cancer clinical trials is well documented. FDA guidance stipulates geographic informed analyses to reduce barriers to trial participation. We performed a geographical analyses of gynecologic cancer clinical trials in the United States relative to racial distribution and social vulnerability indices to identify areas of increased need. Methods: We performed a cross-sectional analysis of NIH ClinicalTrials.gov by retrieving all trials first posted 1/1/2013 through to 1/10/2024. We searched for ovarian, uterine, cervical, endometrial, vaginal/vulvar and gynecological cancer. We reviewed enrollment criteria to exclude non-gynecological cancers (1643 trials) or non-invasive gynecological conditions (224 trials). We aggregated census data, state-level total population size, percent Non-Hispanic White (NHW), and the FEMA Expected Annual Loss per state as a measure of social vulnerability. Using R statistical software (v 4.3.1), we measured the association between these variables and the number of gynecological trials per 100,000 persons using Pearson’s correlation. Results: We identified 3,428 trials, filtered down to 1,561 invasive cancer trials. The most common trials were ovarian (911, 58.3%) and cervical (438, 28.0%), followed by endometrial (385, 24.6%), uterine (158, 10.1%), vulva-vaginal (78, 4.99%), and 7.62% genetic-based. Texas had the highest number of trials (501) followed by California (454) and New York (427). The state with the highest population-adjusted number of trials was South Dakota (8.57 trials per 100,000 persons), followed by Rhode Island at 8.38 per 100,000 persons. California, Mississippi, and Puerto Rico had the lowest number of trials per 100,000 persons with 1.148, 0.979, 0.466 respectively. States/territories with greater than 4 trials per 100,000 were comprised of populations that were &gt; 50% NHW. The correlation between the state-level percentage of NHW in 2020 and the number of trials per 100,000 persons was p = 0.057 indicating that there was a correlation between Whiteness at the state-level and trial availability. We found that states with higher FEMA expected annual loss had lower numbers of gynecological trials per 100,000 persons (p &lt; 0.001). Conclusions: We found a disparity in the geographical distribution of trials available for gynecological cancers that was correlated with racial disparities and social vulnerability. Efforts to increase decentralization of trials and improve access and availability of gynecologic cancer clinical trials are necessary to increase equity for minority representation in clinical trials at the national level.

Geriatric enrollment patterns in clinical trials at a National Cancer Institute.

e13762 Background: Despite the majority of new cancer diagnoses occurring within the geriatric population, there is a disproportionate rate of clinical trial enrollment within this population. Previous data has estimated enrollment rate to be 18.9% in treatment trials among all adult cancer patients at designated National Cancer Institute Cancer Centers. The objective of this study is to assess geriatric cancer patient clinical trial enrollment rates in a single National Cancer Institute and highlight inequities within cancer care delivery. Methods: We performed a retrospective review of the electronic health record and included patients with cancer ≥ 65 years of age who died at our institution between January 2020 and July 2022. We examined the relationship between cancer type, patient race/ethnic identity, and age and analyzed enrollment in clinical trials. Analyses were conducted using descriptive statistics. Results: Of 117 decedent records analyzed, 11 (9%) were enrolled in treatment clinical trials of which 5 (4.3%) identified as White, 4 (3.4%) Other, and 2 (1.7%) Hispanic. Among the 117 geriatric patient records reviewed, there were 21 Black patients (17.9%) of which 0 (0%) Black patients were enrolled in clinical trials. In comparing enrollment by malignancy type, 5 patients had a hematologic malignancy (leukemia, lymphoma, or multiple myeloma), 3 patients had a genitourinary malignancy, 1 patient had a pancreatic malignancy, 1 patient had an endometrial malignancy, and 1 patient had a breast malignancy. Among all patients analyzed, 37 patients (31.6%) had a hematologic malignancy and 80 patients (68.4%) had a solid tumor malignancy. The average age of enrolled patients was 73, consistent with the average age of all patients analyzed (73.78). Conclusions: Geriatric patients with cancer are disproportionately underrepresented in treatment clinical trials. The inequity is exacerbated when analyzing enrollment among minoritized patients. There was a greater proportion of clinical trial enrollment in patients with hematologic malignancies than solid tumor malignancies, however analysis in larger population samples is necessary. Additional research to identify barriers to clinical trials and methods of increasing geriatric enrollment, including the use of geriatric specific performance scales, is necessary to ensure equitable access and representation in clinical trials. While these results may be skewed in the setting of the COVID-19 pandemic and selection of a decedent population, further research into geriatric accessibility in clinical trials is paramount.

Improving diversity in phase I oncology clinical trials: A single institution experience at the University of Colorado Cancer Center.

e13687 Background: Despite continued improvements in cancer outcomes, disparities persist between racial, ethnic, and socioeconomic groups. One potential driver is the lack of appropriate representation in clinical trials, including dose-finding studies. We implemented a set of initiatives including patient education, outreach, a Spanish-speaking bicultural clinic, and regular review of enrollment by race and ethnicity. To investigate the impact of these initiatives, we examined phase I clinical trial patient demographics and treatment outcomes before and after the intervention. Methods: We performed a retrospective review of patients enrolled in 2018-2019 (cohort 1[C1], pre- intervention) and 2022-2023 (cohort 2[C2], post-intervention). We collected patient demographics, area deprivation index (ADI), body mass index (BMI), ECOG performance status, and tumor type. Differences between cohorts were evaluated with T-tests, Chi-Square test, or the Fisher Exact test. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Hazard ratios (HR), confidence intervals (CI) and p values were derived using the cox proportional hazards method. A multivariable model for patients with colorectal cancers (CRC) was selected using the Akaike information criterion (AIC). Results: A total of 361 patients (C1 n = 209, C2 n = 152) were included. Overall, 52.4% of patients were female. The most common tumor sites were CRC (18.3%), pancreas (11.9%) and breast (10.8%). Study participants were 85.0% White, 3.3% Asian, 1.4% Black and 9.1% Hispanic, compared to cancer incidence in Colorado of 92.8%, 1.6% and 3.3% and 10.0%, respectively. Following our intervention, there was an increase in language preference other than English from 1.9% (4/209) to 6.6% (10/152) (p = 0.028) and in translated consents from 1.4% (3/209) to 5.9% (9/152) (p = 0.033). There was no statistically significant difference in race, ethnicity, insurance, or tumor type, although there was a non-statistically significant increase in Hispanic patients from 8.1% to 10.5%. Median PFS improved from 1.9 to 2.8 months (HR = 0.72, 95% CI 0.57-0.90, p = 0.003). ECOG 1 v. 0 was associated with inferior OS (HR = 1.35, 95% CI 1.06-1.73, p = 0.017), and BMI ≥18.5 v. &lt;18.5 was associated with superior OS (HR = 0.59, 95% CI 0.37-0.95, p = 0.03). AIC model of CRC (n = 66) revealed that ADI scores of 6-10 were associated with worse PFS and OS (p = 0.022 and p = 0.001, respectively). Conclusions: Our interventions resulted in an increase in accrual of non-English speaking patients, however, there was not yet a statistically significant change in overall race and ethnicity. Our study confirms poorer clinical outcomes for patients with higher ADI scores. Further research and intervention are warranted to mitigate disparities in clinical trial accrual and improve clinical outcomes for disadvantaged patients.

Pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib (ribo) in Black patients with metastatic breast cancer (mBC): The LEANORA study.

1581 Background: Ribo is metabolized by CYP3A and used for the treatment of patients with hormone receptor-positive (HR+)/HER2- mBC. FDA recommends dose reduction if used with CYP3A inhibitors due to a 3.2x increase ribo area-under-the-curve (AUC). It is unknown if modifications are needed in patients who lack enzyme activity (e.g., genetic CYP3A5 poor metabolizers (PM)). CYP3A5varies by genetic ancestry, is known to affect dosing for other drugs (e.g., tacrolimus). CYP3A5, ~85% of people of European ancestry are PM, ~85% of African ancestry are normal or intermediate metabolizers (NM, IM), which may impact ribo exposure and response. 2 percent (41/2066) enrolled in MONALEESA 2, 3, and 7 were Black. Methods: This prospective, multicenter cohort study (NCT04657679) assessed the PK and PGx of ribo (600 mg daily + letrozole/fulvestrant) in self-identified Black women with HR+/HER2- mBC. PK (0.5, 1, 2, 4, and 6 hours after ribo) and PGx studies were performed during cycle 1 via liquid chromatography with tandem mass spectrometry and PharmacoScan (ThermoFisher) microarray, which tests 1,191 genes. Including variants in CYP3A5*3, *6,and *7. Phenotypes assigned: PM (2 variant alleles), intermediate metabolism (IM; 1 variant allele), NM (0 variant alleles). The area under the curve (AUCtau) was compared with the exact Wilcoxon rank-sum test; Fisher’s exact test assessed the AEs and grade 3+ AEs to day 28. Results: 14 completed the trial. CYP3A5 phenotypes were PM (7), IM (6), and NM (1). The primary endpoint, AUCtau, was similar between CYP3A5 PM (39,230 hr*ng/mL; interquartile range [IQR]: 18,745 to 57,566 hr*ng/mL) vs. IM/NM (43,546 hr*ng/mL; IQR: 35,298 to 46,647 hr*ng/mL; p = 0.38). Other PK properties were similar between groups (table). There was a non-statistically significant higher number of AEs and grade 3+ AEs in PMs, when compared to NM/IMs. Study was not powered to assess differences in AEs. Conclusions: This cohort study detected no association between CYP3A5 genotype and ribo exposure. However, PMs may have more AEs relative to IMs/NMs. Future steps include exploring the impact of rare variants, including ~70 variants in CYP3A 4 and 5, on ribo exposure in this population. We will explore the role of clinical and genetic factors on the interindividual variability of ribo. Diverse patient representation in clinical trials is critical to ensure research findings are applicable to all patients. Clinical trial information: NCT04657679 .[Table: see text]

Global disparities in immunotherapy clinical trials: A comprehensive analysis of low- and middle-income countries over the past decade.

1606 Background: Immunotherapy (IO) has largely impacted cancer treatment over the last decade, yet its accessibility and representation in clinical trials remain severely limited in low- and middle- income countries. We investigated the involvement of these countries in IO cancer trials, analyzing country-specific rates and influencing factors. Methods: Data was obtained from clinicaltrials.gov. Advanced search focused on cancer interventional studies from 12/31/2013 to 01/01/2024 with specific IO treatments. Only completed trials were included. Studies unrelated to immunotherapy or cancer were excluded. Country trial rates were calculated per 100k population. Statistical analysis used Chi-square test for nominal data. Results: Of 1593 trials, 1282 were included in the final analysis. Of world’s 217 countries and regions (World Bank) 72 (33.2%) participated in IO cancer trials in the last decade. Zero country from low-income group was involved in the trials. Only 2.4% (31) of all trials, included lower-middle-income countries (LMICs). Out of 54 LMICs, only 8 were represented: Ukraine, Philippines, India, Guatemala, Egypt, Vietnam, Morocco, and Eswatini (Swaziland). Ukraine led this group with 16 trials, while the remaining 7 were included in less than 10 trials each. Upper-middle-income countries (UMICs) were included in 21.3% (273) of trials. Out of 54 UMICs, 22 were involved in the trials; China led this group (174), followed by Russia (69), Brazil (52), Mexico and Turkey (41 each). Among the top 30 countries with the highest trial participation, none included LMICs, and only 5 were UMICs. Of 81 high-income countries (HICs) 42 participated in IO trials. USA was involved in over 65% of all trials (840), followed by Spain (222), France (193), and Canada (180). However, population-adjusted rates varied, with European HICs like Latvia (2.16), Belgium (1.09), Norway (0.87) among 25 other countries, showing higher rates than USA (0.25). Majority of trials done solely in one country were also from USA (65%), and China (79%). A significant link was found between the economic status of participating countries and the funding source of trials (p&lt;0.00001). Industry funded 28 of 31 (90%) trials in LMICs, indicating a reliance on industry funding in these regions. Industry favored adult-only over pediatric-inclusive trials (p&lt;0.0001). Out of 80 trials (6.24%) including children, 22 were industry-funded. Exclusively pediatric IO trials were only 4 (0.3%) of all IO trials. LMICs participated in 3.75% (3) of all pediatric-inclusive trials. Conclusions: Countries with low economic status and children with cancer from both low- and high-income areas are largely underrepresented in IO cancer trials globally. More inclusive IO trials across age groups and LMICs are vital to implement trial results in real-world settings and close the care gap.

Sex Differences in Transthyretin Cardiac Amyloidosis: Unraveling the Complexities in Epidemiology, Pathophysiology, Diagnosis, and Treatment.

Transthyretin cardiac amyloidosis (ATTR-CA) is characterised by the deposition of transthyretin amyloid fibrils in the heart. ATTR-CA affects both men and women although there is evidence of sex differences in prevalence and clinical presentation. PURPOSE OF REVIEW: This review paper aims to comprehensively examine and synthesise the existing literature on sex differences in ATTR-CA. RECENT FINDINGS: The prevalence of ATTR-CA is higher in males although the male predominance is more apparent in older patients in the wild type form and in TTR genetic variants that predominantly result in a cardiac phenotype in the hereditary variant. Women tend to have less left ventricular hypertrophy (LVH) and a higher ejection fraction at clinical presentation which may contribute to a later diagnosis although the prognosis appears to be similar in both sexes. Female sex is a predictor of a good response to tafamidis 20mg in TTR polyneuropathy but otherwise there are no data on sex differences in the efficacy of other treatments for ATTR-CA. It is crucial to define specific sex differences in ATTR-CA. A lower cut-off value for LVH in women may be needed to improve diagnosis. It is necessary to increase female representation in clinical trials to better understand possible sex differences in therapeutic management.

Diversity trends in traumatic brain injury clinical trials in the United States

ABSTRACT Background This study aims to understand the demographic representation of patients in Traumatic Brain Injury (TBI) clinical trials by evaluating the proportions of patients from various demographic categories amongst completed TBI clinical trials in the United States. Methods ClinicalTrials.gov was queried for active TBI clinical trials. One hundred and eight completed trials in the United States were selected based on inclusion criteria, and information regarding intervention, setting, age, sex, race, and ethnicity was extracted. 2002–2006 TBI incidence data was obtained from the CDC. Chi-squared testing was applied to analyze the relationship between distributions of race and sex in the collected clinical trials and the national TBI data, and logistic regression was conducted to identify variables that may predict reporting of race or ethnicity. Results About 53.7% of selected clinical trials reported racial data and 34.3% reported ethnicity data. Logistic regression identified that clinical trials in defined phases were more likely to report racial data (p = 0.047 [1.015, 9.603]). Conclusion Current TBI trials do not consistently report race or ethnicity data. Future efforts to ensure equitable representation in clinical trials may involve reform of recruitment processes and accountability measures implemented within the grant application process to ensure proper racial and ethnicity data reporting.

Female obesity: clinical and psychological assessment toward the best treatment.

Obesity is a heterogeneous condition which results from complex interactions among sex/gender, sociocultural, environmental, and biological factors. Obesity is more prevalent in women in most developed countries, and several clinical and psychological obesity complications show sex-specific patterns. Females differ regarding fat distribution, with males tending to store more visceral fat, which is highly correlated to increased cardiovascular risk. Although women are more likely to be diagnosed with obesity and appear more motivated to lose weight, as confirmed by their greater representation in clinical trials, males show better outcomes in terms of body weight and intra-abdominal fat loss and improvements in the metabolic risk profile. However, only a few relatively recent studies have investigated gender differences in obesity, and sex/gender is rarely considered in the assessment and management of the disease. This review summarizes the evidence of gender differences in obesity prevalence, contributing factors, clinical complications, and psychological challenges. In addition, we explored gender differences in response to obesity treatments in the specific context of new anti-obesity drugs.

Abstract PO4-10-02: Implementing Just ASK™ to achieve diverse participation and representation in a RCT of chemotherapy-induced peripheral neuropathy

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting complication of cancer treatment which disproportionally affects Black patients, and can negatively impact survival and quality of life. Strategies to improve diverse participation and representation in clinical trials are necessary to reduce this health disparity. Methods: To ensure diverse representation in our RCT of CBD vs placebo in patients with grade 2-3 CIPN after treatment with taxane or platinum-based chemotherapy, key evidence-based strategies outlined in the ASCO-ACCC Just ASK™ Training Program were implemented. Eligibility criteria were as inclusive as possible, including CIPN duration up to 2 years and a range of diagnoses: nonmetastatic breast, colorectal, endometrial; and ovarian cancer. Few comorbidities were excluded. The diverse research team engaged every potentially eligible patient with the opportunity to make an informed decision to participate in the study. Using an assets-based approach, the team assessed and addressed social drivers of health (SDoH) and built trust by providing transparency, timely access to all team members, flexible study visits (including telemedicine), and study materials which were comprehensive, understandable, and accessible, within a culture of respect for patient autonomy and privacy. Results: Between 6/1/2020 and 8/8/2022, 230 patients were prescreened, 124 met eligibility, 54 consented and joined, and 46 completed ≥8 of the 12-week treatment phase and were included in the analysis. The study successfully enrolled a participant population that was 30% Black and 67% White (Table), reflecting community demographics of the enrolling facility. Attrition was lower than expected (15% vs 30% assumed in statistical plan) and only 5 of 425 planned study visits for the 46-patient cohort were missed. The most effective strategy to achieve diverse participation was prescreening the electronic medical record (EMR) with daily Epic® and OncoEMR® queries (DQ) by a research assistant. DQ allowed all potentially eligible patients to be approached to participate and yielded about half of enrollees. Also key to success were engaged study champions among medical oncology fellows, oncology nurses, nurse navigators, clinical research coordinators, and research-oriented attending physicians. Some physician referrals were facilitated by the ease of secured texts and EMR messages, and peer recognition; however, few referrals came from non-research-oriented physicians. Eleven of the 54 consented patients were identified to have essential needs and received facilitated social work assistance, including psychosocial support, financial assistance (for monetary grants for direct expenses or access to medical insurance and other benefits); and support for transportation, nutrition; child and eldercare. Of the 11 patients with essential needs, 4 were unable to complete the study due to either personal (3) or medical issues (1). Conclusions: The ASCO-ACCC Just ASK™ approach was successful for diverse clinical trial enrollment with strong protocol adherence and low attrition. Key steps included: study team diversity, a culture of respect and transparency, EMR prescreening, SDoH assessment and solutions, and engagement of research-oriented study champions. As achieving diverse participation in clinical trials is essential to reducing health disparities, the Just ASK™ approach should be considered an essential aspect of clinical trial design and implementation. Table. Baseline Characteristics Total n = 46 Age (Mean/SD) 59.6 (8.8) Gender Male 5 (10.9%) Female 41 (89.1%) Race White 31 (67.4%) Black 14 (30.4%) Other 1 (2.2%) Ethnicity Hispanic 2 (4.4%) Not Hispanic 44 (95.6%) Cancer Type Breast 29 (63.0%) Colo-rectal 9 (19.6%) Ovarian 7 (15.2%) Uterine 1 (2.2%) Citation Format: Marisa Weiss, Muath Giaddui, Stephanie Kjelstrom, Arezoo Ghaneie, Jennifer Hong, Jessica Burrell, Sarah Windawi, Ebuwa Erebor, Barry Mann, Shonalie Roberts, Gabrielle Bidas, Sam Meske, Lisa Saeed, Katherine Aliano Ruiz, Juliana Hibbs, John Marks, David Holtz, Zonera Ali, Aarthi Shevade, Robin Ciocca, Paul Gilman, Sharon Larson, Shoichi Shimamoto, Diana Martinez, Fumiko Chino, Nadine Barrett. Implementing Just ASK™ to achieve diverse participation and representation in a RCT of chemotherapy-induced peripheral neuropathy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-10-02.

Illuminating the landscape of high-level clinical trial opportunities in the All of Us Research Program.

With its size and diversity, the All of Us Research Program has the potential to power and improve representation in clinical trials through ancillary studies like Nutrition for Precision Health. We sought to characterize high-level trial opportunities for the diverse participants and sponsors of future trial investment. We matched All of Us participants with available trials on ClinicalTrials.gov based on medical conditions, age, sex, and geographic location. Based on the number of matched trials, we (1) developed the Trial Opportunities Compass (TOC) to help sponsors assess trial investment portfolios, (2) characterized the landscape of trial opportunities in a phenome-wide association study (PheWAS), and (3) assessed the relationship between trial opportunities and social determinants of health (SDoH) to identify potential barriers to trial participation. Our study included 181529 All of Us participants and 18634 trials. The TOC identified opportunities for portfolio investment and gaps in currently available trials across federal, industrial, and academic sponsors. PheWAS results revealed an emphasis on mental disorder-related trials, with anxiety disorder having the highest adjusted increase in the number of matched trials (59% [95% CI, 57-62]; P < 1e-300). Participants from certain communities underrepresented in biomedical research, including self-reported racial and ethnic minorities, had more matched trials after adjusting for other factors. Living in a nonmetropolitan area was associated with up to 13.1 times fewer matched trials. All of Us data are a valuable resource for identifying trial opportunities to inform trial portfolio planning. Characterizing these opportunities with consideration for SDoH can provide guidance on prioritizing the most pressing barriers to trial participation.

Lung Cancer Staging—A Clinical Practice Review

Lung cancer is the leading cause of cancer-associated death globally. Staging provides classification of the anatomic extent of cancer that is used consistently worldwide. Lung cancer staging is necessary for prognostication, to inform treatment options, and to allow accurate representation in clinical trials. Staging also separates operable from inoperable disease. Since its introduction in the 1970s, the Tumor, Node and Metastasis (TNM) Staging System has undergone significant revisions, with the latest version, the eighth edition, being effective internationally since 2017. Advances in bronchoscopic and thoracoscopic technologies have expanded procedures to diagnose lung cancer and accurately define the anatomic stage. Understanding the advantages and disadvantages of available methods for staging lung cancer is critical to clinician decision making. In patients with lung cancer without distant metastases, the staging of mediastinal lymph nodes determines treatment options. To minimize the risk and cost, the most appropriate method of staging should identify the highest disease stage while carrying acceptable risk. Minimally invasive endoscopic needle techniques to stage the mediastinum are the first choice to assess for metastases in accessible lymph node stations. Surgical techniques are generally reserved for specific clinical situations, including following negative endoscopic needle techniques when suspicion for nodal involvement is high and to assess endoscopically inaccessible lymph nodes. This review provides a concise account of TNM staging of non-small cell lung cancer (NSCLC) and overview of procedures available for the staging of lung cancer.

Disparities in prostate cancer mortality and clinical trial availability across vulnerable populations.

24 Background: Clinical trials provide high-level evidence and test novel therapies that have significantly improved cancer outcomes. However, disparities in clinical trial participation and cancer mortality persist across race/ethnicity and vulnerable populations, notably in patients with prostate cancer (PCa). Adverse social determinants of health (SDOH) and systemic barriers may underlie these disparities. Identifying and overcoming these barriers may improve access to and representation in clinical trials, thereby promoting equitable advancement and applicability of science. For these reasons, we evaluate the association between clinical trial availability, cancer mortality, and population-level SDOH in PCa. Methods: Using custom data linkage from ClinicalTrials.gov, Surveillance Epidemiology and End Results (SEER) Registry, and the Centers for Disease Control and Prevention Social Vulnerability Index (SVI), we performed a cross-sectional analysis of county-level PCa clinical trial data, cancer incidence and mortality rates, and population-level SDOH. We included Phase 2 and Phase 3 interventional PCa clinical trials with start dates from 2007 to 2022. The total number of clinical trials over the study period was calculated per county and population-adjusted for 100,000 residents. Counties were stratified into quintiles based on SVI (i.e., least vulnerable to most vulnerable). Population-adjusted clinical trial availability, cancer incidence, and cancer mortality were compared across SVI quintiles. Multivariable logistic and linear regression analyses were performed to evaluate the association between SVI and clinical trial availability and cancer mortality, respectively. Results: The mean number of PCa trials per 100,000 residents was 25.6, with the most vulnerable counties having fewer clinical trials compared to the least vulnerable counties (mean 18.1 vs. 50.0, p&lt;0.05). Further, the most vulnerable counties had a lower PCa incidence rate per 100,000 residents (mean 393.8 vs. 411.7, p&lt;0.05), but a higher PCa mortality rate per 100,000 residents (mean 85.7 vs. 72.0, p&lt;0.05). On multivariable regression analysis, the most vulnerable counties were associated with significantly decreased odds of having any PCa clinical trial (OR 0.3, 95% CI 0.2 – 0.4) and significantly increased PCa mortality (10.8, 95% CI 7.4 – 14.3), while the presence of any PCa clinical trial was associated with significantly decreased PCa mortality (-6.9, 95% CI -9.1 – -4.7). Conclusions: The most vulnerable counties were far less likely to have any PCa clinical trials despite having a significantly higher PCa mortality rate. The presence of a PCa clinical trial was associated with a reduction in PCa mortality. These vulnerable counties represent scientifically underserved populations that may benefit from equity-driven clinical trial enrollment and cancer care infrastructure expansion.

Strategies for enhancing the representation of women in clinical trials: an evidence map

BackgroundEquitable sex- and gender-based representation in clinical trials is an essential step to ensuring evidence-based care for women. While multi-institutional actions have led to significant improvements in the inclusion of women in trials, inequity persists in areas like sex-neutral cancers and cardiovascular disease. We sought to identify strategies described or evaluated to boost the inclusion of women in clinical trials.MethodsWe used evidence mapping methodology to examine the breadth of relevant literature. We developed an a priori protocol and followed reporting guidance from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis where applicable. We searched MEDLINE® (via PubMed) and EMBASE (via Elsevier) databases from inception through April 4, 2023, and used standardized procedures incorporating duplication and data verification. We included articles that described strategies to improve the recruitment and retention of women in clinical trials.ResultsWe identified 122 articles describing recruitment and retention strategies for 136 trials (377,595 women). Only one article distinguished between the sex and gender identity of participants, and none defined their use of the terms such as “women” or “female”. The majority of articles (95%) described recruitment for only women, and 64% were conducted in the USA. Ninety-two articles (75%) described strategies in the context of sex-specific conditions (e.g., gynecologic diagnosis). The majority of included articles evaluated a behavioral intervention (52%), with 23% evaluating pharmacologic interventions and 4% invasive interventions. The most common trial phase for reported strategies was during outreach to potential participants (116 articles), followed by intervention delivery (76), enrollment (40), outcomes assessment (21), analysis and interpretation (3), and dissemination (4). We describe specific types of strategies within each of these phases.ConclusionsMost of the existing literature describing strategies to improve the inclusion of women draws from trials for sex-specific conditions and is largely related to outreach to potential participants. There is little information about how and if studies have attempted to proportionally increase the inclusion of women in trials with both men and women or those focused on invasive and pharmacologic interventions. Future work in this area should focus on how to increase the participation of women in mixed-sex studies and on those areas with remaining inequities in trial participation.

Improved clinical trial race/ethnicity reporting and updated inclusion profile, 2017–2022: A New Jersey snapshot

BackgroundDiverse representation in clinical trials is an important goal in the testing of a medical, diagnostic, or therapeutic intervention. To date, the desired level of trial equity and inclusivity has been unevenly achieved. MethodsEmploying the US National Library of Medicine's Clinicaltrials.gov registry, we examined 481 clinical trials conducted - at least in part - in the state of New Jersey. These trials were initiated after the FDA-mandated Common Rule changes, i.e., between January 2017 and October 2022, were enacted, and had their results posted. We analyzed sex/race/ethnicity reporting as well as applicable enrollment. Using meta-analysis, we estimated group participation proportions of a subset of the 481 identified trials; specifically, the 229 studies that were conducted solely within the US (i.e., without international sites) and compared them to US census data. FindingsWithin the 481 clinical trials analyzed, over 97% reported on the race and/or ethnicity of their enrollees; all included information on sex. Reporting was not affected by funding source or therapeutic area. Based on the 229 solely US-based studies, the participants overall were 76.7% White; 14.1% Black; 2.7% Asian; and 15% Hispanic. Inclusion of Black participants did not differ from the 2020 US census data; in contrast, the levels of Asian and Hispanic participation were below the corresponding census percentages. InterpretationThe past five years have seen an overall uptick in the equity of race/ethnicity reporting and inclusivity of clinical trials, as compared to previously reported data, presaging the potential acquisition of ever more powerful and meaningful results of such interventional studies going forward. FundingSupport for this study comes from the Hackensack Meridian Health Research Institute and the Hackensack Meridian School of Medicine. Research in contextEvidence before this studyClinical trials are a critical part of determining whether or not a medical (drug/device/biologic) or socio-behavioral intervention is safe and truly effective. Through their use, scientific understanding is advanced and, ideally, human health is improved. To gain the most impactful information from a clinical trial, it should be sufficiently representative, that is, should enroll an adequate number of participants, and include a diverse population. Without such inclusion, the study is of only limited generalizability. Efforts are underway by funders, sites, and other stakeholders, to enhance reporting and promote inclusive enrollment. The extent to which such attempts are yielding results - at least for clinical trials in the state of New Jersey - is the focus of this data-driven analysis. The ClinicalTrials.gov registry database was carefully mined for the information contained in this report.Added value of this studyOur analysis of clinical trials initiated in the state of New Jersey and conducted there or elsewhere in the US reveals several positive trends. Our 5-year snapshot reveals that a very large percentage of trials report on race/ethnicity - and inclusivity is improving. While there is still some way to go to have the demographic numbers in these trials match US census values, our results suggest that recent efforts are having an effect.Implications of all the available evidenceFor myriad reasons, clinical trials have not enjoyed the public's universal trust over the years. In many ways, medicine moves at the speed of trust - without it, the promise of modern healthcare is brought into question. Clinical trials must include a commitment to diverse enrollment pools and equitable reporting under the law. Creating a legacy of trust - through greater inclusivity in clinical trials and more transparent reporting of results - will begin to heal the divide and engender faith in modern medicine and today's healthcare system. It would also allow for the desired far-reaching generalizability of results across patient populations. To better appreciate what needs to be done going forward, we must truly understand the state of clinical trials reporting and demographic inclusion. This report initiates such an analysis, by carefully documenting how New Jersey's clinical trials are performing. By virtue of its location (e.g., proximity to the cities of New York and Philadelphia) the state is part of a large biopharma cluster and healthcare nexus; it is critical that it performs well with respect to adopting/adhering to updated clinical trial guideline mandates. This report provides a glimpse - an important first look - into the state of clinical trials in New Jersey - from 2017 through 2022.

A Look at the Lack of Representation in Clinical Trials

A Look at the Lack of Representation in Clinical Trials

Opportunities to Increase Science of Diversity and Inclusion in Clinical Trials: Equity and a Lack of a Control.

The United States witnessed a nearly 4-fold increase in personal health care expenditures between 1980 and 2010. Despite innovations and obvious benefits to health, participants enrolled in clinical trials still do not accurately represent the racial and ethnic composition of patients nationally or globally. This lack of diversity in cohorts limits the generalizability and significance of results among all populations and has deep repercussions for patient equity. To advance diversity in clinical trials, robust evidence for the most effective strategies for recruitment of diverse participants is needed. A major limitation of previous literature on clinical trial diversity is the lack of control or comparator groups for different strategies. To date, interventions have focused primarily on (1) community-based interventions, (2) institutional practices, and (3) digital health systems. This review article outlines prior intervention strategies across these 3 categories and considers health policy and ethical incentives for substantiation before US Food and Drug Administration approval. There are no current studies that comprehensively compare these interventions against one another. The American Heart Association Strategically Focused Research Network on the Science of Diversity in Clinical Trials represents a multicenter, collaborative network between Stanford School of Medicine and Morehouse School of Medicine created to understand the barriers to diversity in clinical trials by contemporaneous head-to-head interventional strategies accessing digital, institutional, and community-based recruitment strategies to produce informed recruitment strategies targeted to improve underrepresented patient representation in clinical trials.

Defining interventions and metrics to improve diversity in CNS clinical trial participation: A SNO and RANO effort.

Despite major strides in cancer research and therapy, these advances have not been equitable across race and ethnicity. Historically marginalized groups (HMG) are more likely to have inadequate preventive screening, increased delays in diagnosis, and poor representation in clinical trials. Notably, Black, Hispanic, and Indigenous people represent 30% of the population but only 9% of oncology clinical trial participants. As a result, HMGs lack equitable access to novel therapies, contradicting the principle of distributive justice, as enshrined in the Belmont report, which demands the equitable selection of subjects in research involving human subjects. The lack of clinical trial diversity also leads to low generalizability and potentially harmful medical practices. Specifically, patients with brain cancer face unique barriers to clinical trial enrollment and completion due to disease-specific neurologic and treatment-induced conditions. Collectively, the intersection of these disease-specific conditions with social determinants of health fosters a lack of diversity in clinical trials. To ameliorate this disparity in neuro-oncology clinical trial participation, we present interventions focused on improving engagement of HMGs. Proposals range from inclusive trial design, decreasing barriers to care, expanding trial eligibility, access to tumor profiling for personalized medical trials, setting reasonable metrics and goals for accrual, working with patient community stakeholders, diversifying the neuro-oncology workforce, and development of tools to overcome biases with options to incentivize equity. The diversification of participation amongst neuro-oncology clinical trials is imperative. Equitable access and inclusion of HMG patients with brain tumors will not only enhance research discoveries but will also improve patient care.