Clinical Trial Populations Research Articles

DISP-03. HEALTH DISPARITIES IN NEURO-ONCOLOGY

Abstract Significant disparities in diagnosis, research, and treatment exist in neuro-oncology. Patients who identify as racial or ethnic minorities, sexual or gender minorities, elderly, rural, or have low socioeconomic status are more likely to have adverse outcomes. Using PubMed and expert opinion, we summarized the existing literature on health disparities in neuro-oncology. We categorized disparities based on primary central nervous system tumors (CNS), secondary CNS tumors, pediatric neuro-oncology, clinical trial enrollment and diversity, and financial toxicity. For patients with primary CNS tumors, we found that marginalized groups faced delays in diagnosis, lower rates of resection, and lower rates of postoperative radiation. For secondary CNS tumors, marginalized groups had lower rates of indicated cancer screening, less access to genetic testing, less access to advanced imaging, and lower rates of stereotactic radiosurgery and targeted therapies. Pediatric neuro-oncology patients had differences in morbidity and mortality based on socioeconomic status and race and faced substantial delays in diagnosis. Financial toxicity, the side effects of the high financial cost of a cancer diagnosis, disproportionately affects marginalized populations. This may be further exacerbated by the use of long-term medications such as IDH inhibitors. There is also unequal representation of diverse populations in neuro-oncology clinical trials. Compared to other cancer subspecialties, there is less available data on disparities, however, the types of disparities such as delays in diagnosis and outcomes are similar. Notably, there are not many interventions focused on mitigating these disparities. There needs to be additional research on health disparities in neuro-oncology, including both descriptions of existing disparities, but also on methods and interventions to address these disparities.

Exposure to the antiretroviral drug dolutegravir impairs structure and neurogenesis in a forebrain organoid model of human embryonic cortical development

IntroductionFor many therapeutic drugs, including antiretroviral drugs used to treat people living with HIV-1 (PLWH), we have little data on the potential effects on the developing human brain due to limited access to tissue and historical constraints on the inclusion of pregnant populations in clinical trials. Human induced pluripotent stem cells (iPSCs) offer a new avenue to gain insight on how drugs may impact human cell types representative of the developing central nervous system. To prevent vertical transmission of HIV and promote the health of pregnant PLWH, antiretroviral therapy must be initiated and/or maintained throughout pregnancy. However, many antiretroviral drugs are approved for widespread use following clinical testing only in non-pregnant populations and there may be limited information on potential teratogenicity until pregnancy outcomes are evaluated. The integrase strand transfer inhibitor dolutegravir (DTG) is a frontline antiretroviral drug that is effective in viral suppression of HIV but was previously reported to be associated with a slight increase in the risk for neural tube defects in one study, although this has not been replicated in other cohorts.MethodsTo directly investigate the potential impact of DTG on human cortical neurogenesis, we measured the effects of daily drug exposure on the early stages of corticogenesis in a human iPSC-based forebrain organoid model. We quantified organoid size and structure and analyzed gene and protein expression to evaluate the impact of several doses of DTG on organoid development.ResultsWe observed deficits in organoid structure and impaired neurogenesis in DTG-treated organoids compared to vehicle-treated control organoids after 20 or 40 days in culture. Our highest dose of DTG (10 μM) resulted in significantly smaller organoids with a reduced density of neural rosette structures compared to vehicle-treated controls. Mechanistically, RNA-sequencing and immunohistological analysis suggests dysregulated amino acid transport and activation of the integrated stress response in the DTG-treated organoids, and functionally, a small molecule integrated stress response inhibitor (ISRIB) could partially rescue increased expression of proteins related to cell cycle regulation.DiscussionTogether, these results illustrate the potential for human iPSC-based strategies to reveal biological processes during neurogenesis that may be affected by therapeutic drugs and provide complementary data in relevant human cell types to augment preclinical investigations of drug safety during pregnancy.

Leveraging Social Determinants of Health to Enhance Recruitment of Underrepresented Populations in Clinical Trials.

Historically marginalized communities are disproportionately affected by cardiometabolic diseases yet are underrepresented in clinical trials that investigate needed interventions. This review investigates the barriers to equitable inclusion in clinical trials, identifying opportunities for improvement at the institutional, trial, community, and individual level. It proposes a social determinants-based approach that serves as a toolkit to target these barriers using structural, economic, community, healthcare access, and technology solutions, supporting constructive improvement in the clinical trial recruitment process.

Barriers to Recruitment and Retention Among Underrepresented Populations in Cancer Clinical Trials: A Qualitative Study of the Perspectives of Clinical Trial Research Coordinating Staff at a Cancer Center.

Although US research agencies have instituted peer review processes to require participant diversity in clinical trials before funding decisions are made, the underrepresentation of certain populations (eg, racial and ethnic minorities) in clinical trials remains a persistent challenge in biomedical research. This issue has the potential to affect the generalizability of findings and impede efforts to ensure the provision of high-quality healthcare across all populations. In this study, we examined barriers to the recruitment and retention of underrepresented populations in cancer clinical trials from the perspective of research coordinating staff. Semi-structured interviews were conducted at a US-based academic cancer center and included 6 patient-facing staff (clinical research coordinators) and 6 non-patient-facing staff (regulatory and financial specialists). Interview data were subjected to thematic analysis. To provide additional organizational context, descriptive data were obtained on the characteristics of clinical trials undertaken at the cancer center. The following themes emerged from the staff interviews: 1) absence of a consistent structure for decision-making and problem-solving related to recruitment and retention, 2) staff shortages, 3) administrative burden, and 4) lack of resources. In addition, descriptive data revealed that nearly half the trials, 64/134 (48%), offered informed consent only in English, and only 3/134 (2%) offered participant incentives or reimbursement (eg, for transportation). These interrelated organizational issues were indicative of inadequate systems for ensuring diverse and equitable representation in cancer clinical trials. Results indicate that overcoming barriers to underrepresentation may require dedicated support from sponsoring agencies in the form of evidence-based guidelines, learning collaboratives to facilitate implementation, technical support, resources, and oversight. For progress to be made therefore, both sponsors and cancer centers may need to assume joint responsibility for the implementation of effective systems for ensuring diverse and equitable representation in cancer clinical trials.

Patient-Centered Research Design to Increase Representativeness of Diverse Populations in Clinical Trials.

Patient-Centered Research Design to Increase Representativeness of Diverse Populations in Clinical Trials.

Participant Diversity in Stroke‐Related Medical Device Trials: Historical Context and Ongoing Challenges

Despite an acknowledgment of the ethical and clinical importance of recruiting diverse populations into clinical trials, there is a continued underenrollment of patients with diverse demographic characteristics within the field of neurology and more specifically, in stroke‐related device trials. Efforts on the part of the US Congress, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Medicare & Medicaid Services over the past several decades have attempted to increase trial participant diversity with varying success. This historical context provides an important lens for analyzing diversity proposals and their bearing on device trials in the field of stroke neurology. Despite economic and logistical challenges, recruitment of appropriately diverse clinical trial populations through policy change and community engagement is critical to continuing to advance health equity goals.

Longitudinal validity of the Hyperhidrosis Quality of Life Index (HidroQoL©) in a phase IIIb clinical trial population with hyperhidrosis: responsiveness and meaningful change.

The Hyperhidrosis Quality of Life Index (HidroQoL ©) is a well-developed patient-reported outcome measure assessing the quality of life (QoL) impacts in hyperhidrosis, which has proven very good measurement properties, such as structural validity and internal consistency. We aimed to investigate responsiveness over time and estimate values for meaningful within-person change (MWPC) towards symptom improvement for different measurement time points (4 and 12 weeks), extending the existing validity evidence in patients with primary axillary hyperhidrosis. Data (from a phase IIIb clinical trial) was collected at baseline, week 4, week 8, week 12, week 28, week 52, and week 72. For the assessment of responsiveness, HidroQoL change scores were correlated with corresponding change scores of the Hyperhidrosis Disease Severity Scale (HDSS), the Dermatology Life Quality Index (DLQI), and the gravimetric sweat production based on a-priori formulated hypotheses. Furthermore, it was tested whether the different HDSS change score groups differed significantly from each other over time and whether the HidroQoL was sensitive towards these group differences over time. This was extended by the calculation of matched-pair tests and effect sizes to test significance for each change group separately. For the estimation of MWPC thresholds towards symptom improvement, different anchor-based and integrated approaches were used. In total, the sample was composed of 357 patients with primary axillary hyperhidrosis. For the assessment of responsiveness, 5 out of 14 a-priori hypotheses regarding the correlation of the change scores could be confirmed, whereas the rejected hypotheses only marginally differed from the expected values. Furthermore, regarding responsiveness, the HidroQoL showed sensitivity towards symptom improvement at each measurement time point. Effect sizes were large as expected (d ≥ 0.806). MWPC thresholds towards symptom improvement were proposed for two measurement time points: 5 (week 4) and 6 (week 12). Increasing MWPC values over time were observed. This study extends the evidence for the longitudinal validity of the HidroQoL up to 72 weeks and proposed MWPC thresholds for different time intervals (4 and 12 weeks) after baseline, aiding interpretability. Results concur with findings from previous validation studies.

Clinical research vehicles as a modality for medical research education and conduct of decentralized trials, supporting justice, equity, and diversity in research.

Current clinical research lacks diversity in those that participate. This lack of diversity is concerning given its importance for successful drug development. The frequency and severity of many diseases, along with the pharmacological properties of therapies, can display significant differences based on patient diversity. A clinical trial population that is more reflective of these differences will help researchers better understand the therapeutic profile of the treatment and provide generalizable knowledge to the medical community. The advent of decentralized clinical trial designs is meant to help address this lack of diversity by using portable digital health technologies and virtual interactions to enhance clinical trial access and broaden participation. By leveraging these technologies, trial conduct can occur at locations other than traditional research sites. This shift in trial location may help address some of the logistical, educational, engagement, and trust barriers that have historically prevented enrollment of diverse populations. However, these types of trials still have limitations. Ethical concerns around justice, equity, and diversity will still exist with decentralized clinical trials, which could be mediated using clinical research vehicles. When utilized, this modality may enhance the scientific design and conduct of clinical trials and better follow these ethical principles. These enhancements and improved ethical direction could be accomplished through increasing community involvement, improving health literacy, supporting more diverse trial sites, creating community-based research footholds, fostering connections with researchers, limiting technical challenges, and preventing data security issues.

Language-based exclusion associations with racial and ethnic disparities in thyroid cancer clinical trials

BackgroundRacial and ethnic disparities in thyroid cancer care may be mitigated by improving enrollment of more diverse patient populations in clinical trials. We studied trial eligibility criteria and enrollment to assess barriers to equitable representation. MethodsClinicalTrials.gov was searched for studies on thyroid cancer treatment conducted between 1993 and 2023. The inclusion and exclusion criteria of each study were examined. For published studies, reported demographic information was collected. Observed enrollment by race was compared with the expected distribution as determined using data from the US Census and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) databases. Over- and under-representation was defined as the ratio of observed to expected (O/E) enrollment by the race and ethnicity group. ResultsOf 309 thyroid cancer–related trials, 23 (7.4%) used language as an exclusion criterion. Most were interventional (n = 239, 77.3%), university-initiated (194, 62.8%), and drug/device-focused (195, 63.1%). Of studies that excluded by language, 20 (87.0%) were university-initiated. Eighty-eight trials were subsequently published, with 16 (18.2%) reporting race and/or ethnicity distributions. When comparing O/E ratios, White American participants were over-represented (O/E ratio: 1.2, P < .0001). Under-represented groups included Asian/Native Hawaiian (O/E ratio: 0.6, P = .0085), Black (0.6, P = .014), Native American (0.2, P = .072), and Hispanic patients (0.2, P < .0001). ConclusionOver the last 3 decades, 1 in 13 thyroid cancer–related clinical trials excluded patients based on language. In the fraction of published studies to report on racial and ethnic demographics, Asian/Native Hawaiian, Black, and Hispanic patients were under-represented. Improved reporting of demographics in published studies and elimination of exclusion criteria such as language that hinder enrollment of minority patients could improve equitable representation of patients in thyroid cancer clinical trials.

Automated remote speech-based testing of individuals with cognitive decline: Bayesian agreement of transcription accuracy.

We investigated the agreement between automated and gold-standard manual transcriptions of telephone chatbot-based semantic verbal fluency testing. We examined 78 cases from the Screening over Speech in Unselected Populations for Clinical Trials in AD (PROSPECT-AD) study, including cognitively normal individuals and individuals with subjective cognitive decline, mild cognitive impairment, and dementia. We used Bayesian Bland-Altman analysis of word count and the qualitative features of semantic cluster size, cluster switches, and word frequencies. We found high levels of agreement for word count, with a 93% probability of a newly observed difference being below the minimally important difference. The qualitative features had fair levels of agreement. Word count reached high levels of discrimination between cognitively impaired and unimpaired individuals, regardless of transcription mode. Our results support the use of automated speech recognition particularly for the assessment of quantitative speech features, even when using data from telephone calls with cognitively impaired individuals in their homes. High levels of agreement were found between automated and gold-standard manual transcriptions of telephone chatbot-based semantic verbal fluency testing, particularly for word count.The qualitative features had fair levels of agreement.Word count reached high levels of discrimination between cognitively impaired and unimpaired individuals, regardless of transcription mode.Automated speech recognition for the assessment of quantitative and qualitative speech features, even when using data from telephone calls with cognitively impaired individuals in their homes, seems feasible and reliable.

Harnessing 12-lead ECG and MRI data to personalise repolarisation profiles in cardiac digital twin models for enhanced virtual drug testing

Cardiac digital twins are computational tools capturing key functional and anatomical characteristics of patient hearts for investigating disease phenotypes and predicting responses to therapy. When paired with large-scale computational resources and large clinical datasets, digital twin technology can enable virtual clinical trials on virtual cohorts to fast-track therapy development. Here, we present an open-source automated pipeline for personalising ventricular electrophysiological function based on routinely acquired magnetic resonance imaging (MRI) data and the standard 12-lead electrocardiogram (ECG).Using MRI-based anatomical models, a sequential Monte-Carlo approximate Bayesian computational inference method is extended to infer electrical activation and repolarisation characteristics from the ECG. Fast simulations are conducted with a reaction-Eikonal model, including the Purkinje network and biophysically-detailed subcellular ionic current dynamics for repolarisation. For each patient, parameter uncertainty is represented by inferring an envelope of plausible ventricular models rather than a single one, which means that parameter uncertainty can be propagated to therapy evaluation. Furthermore, we have developed techniques for translating from reaction-Eikonal to monodomain simulations, which allows more realistic simulations of cardiac electrophysiology. The pipeline is demonstrated in three healthy subjects, where our inferred pseudo-diffusion reaction-Eikonal models reproduced the patient's ECG with a median Pearson's correlation coefficient of 0.9, and then translated to monodomain simulations with a median correlation coefficient of 0.84 across all subjects. We then demonstrate our digital twins for virtual evaluation of Dofetilide with uncertainty quantification. These evaluations using our cardiac digital twins reproduced dose-dependent QTc and T peak to T end prolongations that are in keeping with large population drug response data.The methodologies for cardiac digital twinning presented here are a step towards personalised virtual therapy testing and can be scaled to generate virtual populations for clinical trials to fast-track therapy evaluation. The tools developed for this paper are open-source, documented, and made publicly available.

Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study

Underrepresented populations’ participation in clinical trials remains limited, and the potential impact of genomic variants on drug metabolism remains elusive. This study aimed to assess the pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib in self-identified Black women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. LEANORA (NCT04657679) was a prospective, observational, multicenter cohort study involving 14 Black women. PK and PGx were evaluated using tandem mass spectrometry and PharmacoScan™ microarray (including CYP3A5*3, *6, and *7). CYP3A5 phenotypes varied among participants: 7 poor metabolizers (PM), 6 intermediate metabolizers (IM), and one normal metabolizer (NM). The area under the curve did not significantly differ between PMs (39,230 h*ng/mL) and IM/NMs (43,546 h*ng/mL; p = 0.38). The incidence of adverse events (AEs) was also similar. We found no association between CYP3A5 genotype and ribociclib exposure. Continued efforts are needed to include diverse populations in clinical trials to ensure equitable treatment outcomes.

Abstract A107: Be Part of the Cure Clinical Trials Campaign: Koreans, Hispanic/Latino/a/e/x, and Black/African Americans living in Los Angeles County

Abstract Background. There is negative perception and lack of participation in clinical trials among Koreans, Hispanic/Latino/a/e/x, and Black/African Americans living in Los Angeles County, which may be attributed to cultural beliefs, language barriers, historical mistrust of medical research, and lack of awareness about the benefits of participation. Without representation from diverse groups, there may be missed opportunities to develop personalized treatment approaches tailored to specific genetic, cultural, and lifestyle factors. Methods. Cedars Sinai Cancer Community Outreach and Engagment (COE) developed a multi-level approach to increase representation of minority populations in clinical trials. With active Community Advisory Board involvement in the development and implementation, a culturally sensitive clinical trials awareness campaign, “Be Part of the Cure”, was developed to offer in-language cancer information, education on clinical trials, and navigation through the cancer care continuum. To support patients and facilitate access to trials, COE has developed bi-directional engagement between CCSC physicians, nurses and Clinical Trials Office representatives, FQHCs, and community and faith-based organizations to ensure a seamless navigation process to care. Additionally, our multicultural and multilingual COE staff have trained Community Health Workers and navigators to expand our outreach efforts and effectively engage our target communities. Results. In total, COE has facilitated 7 health education workshops and attended 3 community outreach events with 501 people educated (37% or 184 Black/African American; 25% or 123 Asians; 17% or 87 Hispanic/Latinx; and 21% or 107 White). Pre/post-tests administered to 73 Koreans during health education workshops showed significant increase in positive perception on clinical trials from 57% to 95%. Korean (n=9) cancer patients have expressed interest in clinical trials, and 1 have been enrolled in Neoadjuvant HER2-Targeted Therapy and Immunotherapy with Pembrolizumab clinical trial. Among Hispanic/Latinx/a/o community, 1 clinical trials health awareness workshop was convened with clinicians who presented to promotores, patients, caregivers, survivors and community members. There were 25 people who completed the pre/post test. There was an increase in positive perception on clinical trials from 52% to 100%, willingness to participate from 60% to 96%, and likelihood of encouraging others to participate from 60% to 96%. In the Black/African American community, 1 clinical trials health awareness workshop was also convened. Among attendees, 21 people completed Pre/Post Test and positive perception on clincal trials increased from 47% to 85%, willingness to participate from 43% to 81%, and likehood on encouraging others to participate from 52% to 81%. Conclusion. Efforts to increase diversity and inclusion in clinical trials should focus on culturally sensitive recruitment strategies, language accessibility, community engagement, and building trust between researchers and communities. Citation Format: Ghecemy Lopez, Dong Hee Kim, Zul Surani, Lourdes Barajas. Be Part of the Cure Clinical Trials Campaign: Koreans, Hispanic/Latino/a/e/x, and Black/African Americans living in Los Angeles County [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A107.

Abstract B160: Assessing patient experience in cancer clinical trial participants: Results from a rapid umbrella review with an equity lens

Abstract Introduction: Clinical trials are an important part of cancer care, yet research assessing patient experience in cancer clinical trials is sparse. Ensuring that the patient voice is heard and valued in the context of clinical trials is critical to the delivery of high-quality, patient-centered, and equitable cancer care. Furthermore, understanding the aspects of cancer clinical trials that are important to and reported by patients may inform strategies to address barriers to clinical trial participation, improve diversity in clinical trials, and advance health equity, particularly among populations underrepresented in clinical research. This rapid umbrella review sought to understand how patient experience is assessed in cancer clinical trials and to identify opportunities to integrate an equity lens. Methods: PubMed, Embase, Cochrane, and CINAHL databases were searched for systematic reviews that identify and describe development, use, or testing of tools/instruments assessing patient experience of cancer clinical trial patients. The search strategy was collaboratively developed with an NIH Librarian, using a combination of key terms to describe: 1) patient experience, 2) clinical trials, 3) healthcare delivery, and ) systematic reviews. The search was limited to publications in the English language and a date range of 2018-2024. One co-author completed the title and abstract review based on the inclusion criteria. Two reviewers will then independently completed the full text review, quality appraisal, and data abstraction for all included studies. All authors will synthesize data into matrix tables and narratively summarize into key themes. Discrepancies were resolved through discussion. Results: Out of 1,751 yielded search results, 151 articles were preliminarily identified. Upon further reading of the full texts, the final list of included articles meeting inclusion criteria will be reported using Covidence. Summary findings from this rapid umbrella review will include the number of studies identified, clinical trials population, a description of the patient experience measures, domains, findings, as well as opportunities for health equity integration using the PROGRESS-Plus Framework. Conclusion: Equitable representation in clinical trials will require intentional efforts to understand and enhance the experience of patients on clinical trials across diverse patient populations, as well as address barriers to participation. However, there are several research gaps that limit our understanding in this area, including a lack of consistent definitions, patient experience domains; availability and use of standardized, validated measures for clinical trial populations, and knowledge about what factors differ and influence patients’ experiences, particularly among populations underrepresented in clinical research. Attention to these gaps will facilitate a greater understanding of patient needs, experiences, and barriers, and may promote actionable strategies to increase access to, inclusion of, and diversity in cancer clinical trials. Citation Format: Brenda Adjei, Katrina Makres, Eric Juarez, Sae-Jin E Lee, Lynne Padgett. Assessing patient experience in cancer clinical trial participants: Results from a rapid umbrella review with an equity lens [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B160.

Abstract B058: Preliminary findings of a multilevel community-based clinical trials and genomic navigation program implemented in the southern United States

Abstract Introduction: Advances in genomics have increased our understanding of the interplay between genetics, environment, behavior, and disease. However, these scientific advances are hampered by the inadequate representation of African American (AA) and Hispanic populations in genomic studies and clinical trials; thus, it is important to identify effective engagement and navigation strategies. The goal of the MSM/TU/UAB OCCC Partnerships to Advance Cancer Health Equity (PACHE) Outreach Core is to implement and evaluate an evidence-based, theory-informed, multi-level, clinical trial and cancer genomics education program (CTC-GEP) to address the determinants for AA and Hispanic participation in clinical trials and genomic research. The program consists of a clinical and genomic navigator and a high and low-tech toolkit. We will present preliminary data characterizing the feasibility phase of this two-arm behavioral trial. Methods: The Attitudes and Intentions to Enroll in a Therapeutic Trial (AIET) questionnaire and a culturally tailored social and demographic questionnaire were used by navigators to obtain participants information. Cumulative logistic regression was used to assess the correlation of age, race, education, and type of health insurance with attaining a higher score on the Likert scale used in AIET survey questions at pre- and post-test. Results: Younger participants (18-49 years) were significantly more likely than older participants (ages 50 and above) to hold several positive views about participating in clinical trials. Specifically, they were 3.6 times as likely to believe that participating in a clinical trial could help advance science to improve community health (P-value = 0.0393); 4.6 times as likely to think there are benefits for others like them (P-value = 0.25); 5.6 times as likely to trust that clinical trial centers have rules to protect their records (P-value = 0.024); and 3.9 times as likely to trust health workers (P-value = 0.002). Additionally, participants with a high school education or less were 3.2 times as likely to consider themselves at risk of cancer compared to those with a college education or higher (P- value = 0.0015). Medicare &amp; Medicaid recipients, compared to those with private insurance, viewed privacy as a major concern when participating in research (P-value = 0.008). Furthermore, Black/AA participants were more likely than White participants to believe that Blacks are used in research without their knowledge (P-value = 0.005). Conclusions: CTC- GEP was demonstrated to be feasible and acceptable among study participants. Findings from the AIET survey highlight privacy concerns are more pronounced among Medicare &amp; Medicaid recipients, indicating a need for better communication about privacy protections. As well, age and racial disparities exist in trust regarding the ethical conduct of research, with older and AA participants expressing significant concern about being used in research inappropriately and without their knowledge. Citation Format: Mohamed Mubasher, Osato Eke, Victoria Churchill, Vivian Carter, Yu-Mei Schoenberger, Desiree Rivers, Jamirah Chevrin, Stephen Sodeke, Christina Wilkerson, Makeeta Rayton, Teresa Hall, Illeana Barrios Zermeno, Angela Morris, Jennifer Culbertson, Roland Matthews, Brian Rivers. Preliminary findings of a multilevel community-based clinical trials and genomic navigation program implemented in the southern United States [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B058.

Abstract C164: Underrepresentation of Black and elderly populations in immunotherapy-based clinical trials for gynecologic cancers: Trends over the past two decades

Abstract BACKGROUND: Race-based disparities in gynecologic oncology (GYN-ONC) clinical trials are well-documented. In 2012, the FDA introduced the Safety and Innovation Act (FDASIA) to improve the reporting and inclusion of demographic minorities in clinical trials. Also, the first immune checkpoint inhibitor (ICI), Ipilimumab, received FDA approval in 2011, which opened a new era of ICI-based clinical trials in several cancer types, including Gyn cancers. Here we assessed trends in race- and age-based disparities pre- and post-introduction of the FDASIA in a subset of GYN-ONC clinical trials investigating immunotherapy. METHODS: Phase 1-3 trials were identified using the following search terms on ClincialTrials.gov: ovarian cancer (OvCa), endometrial cancer (EnCa), cervical cancer (CxCa), immunotherapy, adoptive cell therapy, vaccine, ICI. Trials without posted/published results were excluded. Enrollment, race, ethnicity, and age data were extracted from the clinical trials page and/or associated manuscripts. Using CxCa, EnCa and OvCa prevalence data from the 2021 SEER database, we calculated expected enrollment proportions by race and age, respectively, and compared these to actual clinical trial enrollment data. Binomial and chi-squared tests were used for statistical analyses. RESULTS: 252 clinical trials were initially identified. 123 trials (48.8%), opened between 2002-2020, remained after removing ongoing trials without published/posted results. Of the 123 trials, 58 (47%) reported both race and ethnicity (RAE) data; 26 (21.1%) reported only racial demographics; and 39 (31.7%) did not report RAE data. 71.2% (71/99) of studies that opened from 2013-2020 reported RAE data compared to 50% (12/24) from 2002-2012 (OR: 2.54, 95% CI: 1.04-6.18, p=0.05). 84 trials (58 with RAE, and 26 with only race) had evaluable data for 12,433 participants. Black patients had lower enrollment (3.9%; 47% of expected enrollment) vs. White patients (69.7%; 81% of expected enrollment, P&amp;lt;0.0001) compared to the distribution of race (White: 86.3%, Black: 8.4%, Asian: 4.9%) of all three GYN cancers in the US. In trials that opened between 2013-2020 vs. 2002-2012, the proportion of Whites entering trials decreased (68.6% vs. 94.1%, OR: 0.14, 95% CI: 0.10-0.19, p&amp;lt;0.0001), while there was no change in the proportion of Black enrollment ( 4.0% vs. 3.1%, OR: 1.32, 95% CI: 0.82 to 2.14, p=0.27). On the other hand, there was an increase in the proportion of Asian participants (17.7% vs. 2.0%, OR: 10.65, 95% CI: 5.93-19.28, p&amp;lt;0.0001) and the proportion of other/unknown participants (9.8% vs. 0.9%, OR: 11.96, 95% CI: 5.17-27, p&amp;lt;0.0001). Enrollment of elderly groups did not change significantly between 2002-2012 (37.2%) vs. 2013-2020 (27.0%, OR: 0.78, 95% CI: 0.50-1.24, p=0.27). CONCLUSIONS: RAE reporting trended to increase after the introduction of the 2012 FDASIA, however, Black and elderly populations were still underrepresented. Continued efforts should be made to improve RAE reporting as well as enrollment of Black and elderly populations in Gyn cancer immunotherapy trials. Citation Format: Maheen Khan, Kristen Ibanez, Duncan Donohue, Courtney Bowen, Jung-Min Lee. Underrepresentation of Black and elderly populations in immunotherapy-based clinical trials for gynecologic cancers: Trends over the past two decades [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C164.

Racial and Sex Differences in Genomic Profiling of Intrahepatic Cholangiocarcinoma

BackgroundRacial and sex disparities in the incidence and outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) exist, yet potential genomic variations of iCCA based on race and sex that might be contributing to disparate outcomes have not been well studied.MethodsData from the American Association for Cancer Research Project GENIE registry (version 15.0) were analyzed to assess genetic variations in iCCA. Adult patients (age >18 years) with histologically confirmed iCCA who underwent next-generation sequencing were included in the analytic cohort. Racial and sex variations in genomic profiling of iCCA were examined.ResultsThe study enrolled 1068 patients from 19 centers (White, 71.9%; Black, 5.1%; Asian, 8.4%, other, 14.6%). The male-to-female ratio was 1:1. The majority of the patients had primary tumors (73.7%), whereas 23.0% had metastatic disease sequenced. While IDH1 mutations occurred more frequently in White versus Black patients (20.8% vs. 5.6%; p = 0.021), FGFR2 mutations tended to be more common among Black versus White populations (27.8% vs. 16.1%; p = 0.08). Males were more likely to have TP53 mutations than females (24.3% vs. 18.2%, p = 0.016), whereas females more frequently had IDH1 (23.3% vs 16.0 %), FGFR2 (21.0% vs. 11.3%), and BAP1 (23.4% vs. 14.5%) mutations than males (all p < 0.05). Marked variations in the prevalence of other common genomic alterations in iCCA were noted across different races and sexes.ConclusionDistinct genomic variations exist in iCCA across race and sex. Differences in mutational profiles of iCCA patients highlight the importance of including a diverse patient population in iCCA clinical trials as well as the importance of recognizing different genetic drivers that may be targetable to treat distinct patient cohorts.

Simultaneous Inference Using Multiple Marginal Models.

This tutorial describes single-step low-dimensional simultaneous inference with a focus on the availability of adjusted p values and compatible confidence intervals for more than just the usual mean value comparisons. The basic idea is, first, to use the influence of correlation on the quantile of the multivariate t-distribution: the higher the less conservative. In addition, second, the estimability of the correlation matrix using the multiple marginal models approach (mmm) using multiple models in the class of linear up to generalized linear mixed models. The underlying maxT-test using mmm is discussed by means of several real data scenarios using selected R packages. Surprisingly, different features are highlighted, among them: (i) analyzing different-scaled, correlated, multiple endpoints, (ii) analyzing multiple correlated binary endpoints, (iii) modeling dose as qualitative factor and/or quantitative covariate, (iv) joint consideration of several tuning parameters within the poly-k trend test, (v) joint testing of dose and time, (vi) considering several effect sizes, (vii) joint testing of subgroups and overall population in multiarm randomized clinical trials with correlated primary endpoints, (viii) multiple linear mixed effect models, (ix) generalized estimating equations, and (x) nonlinear regression models.

Pharmacokinetics and Pharmacogenomics of Ribociclib in Black Patients with Metastatic Breast Cancer: The LEANORA study.

Underrepresented populations' participation in clinical trials remains limited, and the potential impact of genomic variants on drug metabolism remains elusive. This study aimed to assess the pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib in self-identified Black women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. LEANORA (NCT04657679) was a prospective, observational, multicenter cohort study involving 14 Black women. PK and PGx were evaluated using tandem mass spectrometry and PharmacoScan™ microarray (including CYP3A5*3 , *6 , and *7 ). CYP3A5 phenotypes varied among participants: 7 poor metabolizers (PM), 6 intermediate metabolizers (IM), and one normal metabolizer (NM). The area-under-the-curve did not significantly differ between PMs (39,230 hr*ng/mL) and IM/NMs (43,546 hr*ng/mL; p = 0.38). The incidence of adverse events (AEs) was also similar. We found no association between CYP3A5 genotype and ribociclib exposure. Continued efforts are needed to include diverse populations in clinical trials to ensure equitable treatment outcomes.

Utilization of Real-World Data to Facilitate Clinical Trials for Patients with Lymphoma

The future directions in leveraging real-world evidence (RWE) and real-world data (RWD) in the field of lymphoma, as compared to traditional experimental clinical trials, are poised to significantly impact research methodologies, treatment strategies, and patient care. Current methods of clinical trials involve a well-controlled design and patient selection bias. Integrating RWE and RWD with experimental clinical trials offers a multifaceted approach to understanding lymphoma and enhancing patient outcomes. In this review, we discuss how RWE has helped shape lymphoma clinical trials, and we compare and evaluate evidence obtained from real-world lymphoma studies/databases with that obtained from clinical trials. We also discuss methods for utilizing surrogate endpoints to facilitate clinical trials and expedite drug development. RWE can be leveraged to bridge the gap between data obtained from clinical trial populations and the broader patient population encountered in clinical practice, by highlighting differences in outcomes and the need for effective treatment strategies across diverse patient groups.