Clinical Investigators Research Articles

The Diverse Aspects of Uterine Serous Cancer: An NCI workshop on the status of and opportunities for advancement of research.

The marked increase in incidence and mortality in endometrial cancer over the last two decades is driven in part by rising rates of higher grade, more aggressive endometrial cancers with mutations in TP53, uterine serous cancers and their dedifferentiated component, uterine carcinosarcomas (collectively USC). USC rates have been increasing among all racial and ethnic groups, with higher rates of this aggressive uterine cancer in Black women. The National Cancer Institute (NCI) hosted a workshop in June 2023 to examine the diverse aspects of USC across epidemiology, biology, and molecular genetics, and to advance knowledge from basic to preclinical and translational efforts. Key stakeholders came together including basic scientists, clinical investigators, and patient advocates to identify critical research gaps that, when addressed, would facilitate more comprehensive and rapid progress in understanding and ultimately treating USC across all patients. NCI released a supplemental funding opportunity (NOT-CA-24-044) in Spring 2024 to facilitate rapid translation of these recommendations.

Regenerative Skincare Technologies Derived From Human Fibroblasts: Growth Factors and Exosomes for Transformative Outcomes.

Since the early 2000s, human fibroblast conditioned media (HFCM) has been used in topical growth factor skincare to support skin regeneration and skin rejuvenation. Human fibroblast conditioned media contains the fibroblast secretome including growth factors as well as exosomes. The potential benefits of topically applied exosomes are gaining interest in the medical aesthetic field. This article aims to summarize the preclinical and clinical data available on regenerative HFCM-based topical skincare with a focus on studies investigating products applied to improve overall facial skin rejuvenation and/or after in-office cosmetic procedures. In addition, available data on fibroblast-derived exosomes will be covered. A focused literature review was conducted to provide an overview of evidence on HFCM-based topical skincare. Human fibroblast conditioned media-based skincare significantly reduces signs of skin aging including photodamage, coarse lines and wrinkles, and sagging. After in-office cosmetic procedures, HFCM-based skincare can stimulate skin recovery and reduce downtime as well as provide skin quality benefits to enhance overall treatment outcomes. Application of purified exosomes from HFCM also demonstrated significant improvements in multiple skin aging parameters. Human fibroblast conditioned media combines naturally secreted fibroblast-derived growth factors and exosomes that stimulate skin regeneration and rejuvenation as evidenced by a variety of assays and assessments including in vitro preclinical studies, clinical investigator grading, instrumentation measurements, biopsy analyses, and patient-reported outcomes.

Comparative Effectiveness of Miswak and Toothbrushing on Dental Plaque and Gingivitis: A Randomized Controlled Trial.

The miswak, crafted from the Salvadora persica tree, is a traditional teeth-cleaning twig that has served as a natural substitute for toothbrushes and toothpaste across diverse regions for centuries. This study aimed to evaluate and compare the effectiveness of miswak and a conventional toothbrush in reducing dental plaque and gingivitis over a two-week period. This two-week randomized, single-blind (clinical investigator), two-parallel-arm clinical trial was conducted at Princess Nourah University College of Dentistry (PNUCD). Stratified random sampling identified sixty participants who were then randomly assigned to two study groups: the miswak group and the toothbrushing group. To facilitate data collection, a self-designed form was employed to document participants' initials, assigned group, the Silness and Loe plaque index, and the Loe and Silness gingival index. The clinical examination, conducted by two blinded and trained examiners using a mouth mirror and explorer under natural light, aimed to assess the specified indices. The collected data were analyzed using IBM SPSS Statistics, Version 22. Following the intervention, the miswak group exhibited no significant change in the plaque scores (p = 0.58) compared to the toothbrush group (p = 0.007). A notable rise in gingival score was observed within the miswak group (p < 0.001), whereas no significant change was noted within the toothbrush group (p = 0.52). Over a two-week period, miswak was successful in controlling dental plaque; however, gingival scores were higher, which could be attributed to the aggressive use of miswak. With proper training, the use of miswak has the potential to contribute positively to gingival health, particularly in regions where it is readily accessible and affordable.

Diverse Concepts in Definitions of Dilated Cardiomyopathy: Theory and Practice.

Our understanding of dilated cardiomyopathy (DCM) is evolving as new insights into the underlying pathophysiology become available. Professional organizations and clinical experts are improving definitions of DCM, allowing for more accurate treatment recommendations. This review summarized key published literature describing definitions and/or diagnostic criteria for DCM. Embase was searched from database inception to September 19, 2022 for 1) publications reporting definitions of DCM by major professional organizations and related opinion papers, and 2) clinical studies in DCM and heart failure with reduced ejection fraction. Sixty-eight records were included in this review. Definitions of DCM provided by two major professional organizations (American Heart Association (AHA) and European Society of Cardiology (ESC)) agreed on the clinical presentation of DCM; however, they differed in the classification of DCM within the larger context of cardiomyopathy taxonomies. Both organizations agreed that DCM could be clinically defined by the presence of left ventricular dilation and contractile dysfunction in the absence of abnormal loading conditions and severe coronary artery disease. AHA guidelines divided cardiomyopathies into two major groups (primary and secondary) based on predominant organ involvement. DCM was classified as primary cardiomyopathy with mixed (genetic and/or acquired) etiology. Conversely, ESC published a clinically oriented taxonomy in which cardiomyopathies were grouped into specific morphological and functional phenotypes; each was subclassified into familial or non-familial forms. Opinion papers further elaborated on the complex interplay between genetics and environment in the etiology of DCM. Several articles summarized the importance of the new and updated diagnostic tools, such as cardiac magnetic resonance imaging, electrocardiogram, and other biomarkers, in correctly identifying the etiology of DCM. Within clinical studies, most inclusion criteria used standard definitions proposed by leading professional associations (AHA and ESC). Clinical study investigators sometimes used a narrower definition of DCM using additional criteria for the left ventricular ejection fraction threshold value and left ventricular dilatation. Current efforts in cardiology research are focused on a more granular understanding of DCM etiology and the natural history of the disease. Definitions of DCM found in clinical studies mainly rely on published guidelines, with some studies adding idiosyncratic inclusion criteria refining the broad definitions of DCM.

Safety of oral mucosal punch biopsy and other oral biospecimen collections in clinical research

ObjectiveOral punch biopsies are frequently used for analysis of lesions since they are minimally invasive, easily performed and assist in diagnosis. Despite broad usage, recent changes in risk classification characterize oral punch biopsies as “greater than minimal risk” for institutional review board purposes. We performed a retrospective review of oral sampling in clinical trials to determine the safety of punch biopsies and other biospecimen collection methods in our oral cancer surveillance program. Study DesignPunch biopsies of 3- and 4-mm were collected following topical and local injection anesthetic. Hemostasis was achieved using pressure and silver nitrate cautery. Other specimens were collected according to standard collection guidelines. Safety and adverse events were determined through consultation with clinical investigator guidelines and were graded with the NCI Common Terminology Criteria for Adverse Events v5. ResultsIn total, 579 samples were collected, 339 of which were oral punch biopsies. There were no adverse events above NCI CTCAE grade 1 for any biospecimen collection. ConclusionThese results support the safety profile of oral punch biopsies and saliva collection. Additionally, these results align with previous research on punch biopsy safety and demonstrate fewer bleeding events. Based on the results and prior research, we believe that punch biopsies should be considered a minimal risk procedure.

Correlation of sibling couple infertility history with semen parameters of infertile men, a cohort study.

Infertility is a growing issue globally, particularly in industrialized cultures, affecting 13%-18% of couples of reproductive ages. In recent years, numerous studies have aimed to identify prognostic factors for infertility and abnormal semen analysis. To date, no study has examined the relationship between the number of infertile siblings and abnormal sperm parameters. This study aims to investigate whether the number of infertile siblings can be considered a prognostic factor for abnormal sperm parameters. Semen samples were collected from the male partners of couples experiencing infertility issues. Study participants completed a questionnaire detailing demographic information including age and family history of infertility. Each participant provided two semen samples, with a minimum 15-day interval between collections. Sperm concentration, motility, and morphology were assessed for each sample. Clinical investigators conducted physical examinations, using an orchidometer to measure testicular size. The number of infertile brothers and testis volume were prognostic factors for abnormal sperm count (OR = 1.374, p-value = 0.03; OR = 0.786, p-value < 0.001; respectively) and abnormal motility (OR = 1.514, p-value = 0.018; OR = 26.74, p-value < 0.001, respectively). There was no significant association between the percentage of abnormal morphology of sperm cells and the mentioned prognostic factors. The optimal cut-off point of the number of infertile brothers for both abnormal sperm count and abnormal sperm motility was one. It is recommended that males with at least one infertile brother, undergo sperm analysis to identify individuals at risk of infertility.

Biallelic RXFP2 variants lead to congenital bilateral cryptorchidism and male infertility, supporting a role of RXFP2 in spermatogenesis.

Does RXFP2 disruption impair male fertility? We identified biallelic variants in RXFP2 in patients with male infertility due to spermatogenic arrest at the spermatid stage, supporting a role of RXFP2 in human spermatogenesis, specifically in germ cell maturation. Since RXFP2, the receptor for INSL3, plays a crucial role in testicular descent during prenatal development, biallelic variants lead to bilateral cryptorchidism, as described in four families to date. While animal models have also suggested a function in spermatogenesis, the postnatal functions of RXFP2 and its ligand INSL3, produced in large amounts by the testes from puberty throughout adulthood, are largely unknown. A family with two male members affected by impaired fertility due to spermatogenic maturation arrest and a history of bilateral cryptorchidism underwent clinical, endocrinological, histological, genomic, in vitro cellular, and in silico investigations. The endocrinological and histological findings were correlated with publicly available single-cell RNA sequencing (scRNA-seq) data. The genomic defects have been characterized using long-read sequencing and validated with in silico modeling and an in vitro cyclic AMP reporter gene assay. An intragenic deletion of exon 1-5 of RXFP2 (NM_130806.5) was detected in trans with a hemizygous missense variant c.229G>A, p.(Glu77Lys). The p.(Glu77Lys) variant caused no clear change in cell surface expression or ability to bind INSL3, but displayed absence of a cAMP signal in response to INSL3, indicating a loss-of-function. Testicular biopsy in the proband showed a maturation arrest at the spermatid stage, corresponding to the highest level of RXFP2 expression in scRNA-seq data, thereby providing a potential explanation for the impaired fertility. Although this is so far the only study of human cases that supports the role of RXFP2 in spermatogenic maturation, this is corroborated by several animal studies that have already demonstrated a postnatal function of INSL3 and RXFP2 in spermatogenesis. This study corroborates RXFP2 as gene implicated in autosomal recessive congenital bilateral cryptorchidism due to biallelic variants, rather than autosomal-dominant cryptorchidism due to monoallelic RXFP2 variants. Our findings also support that RXFP2 is essential in human spermatogenesis, specifically in germ cell maturation, and that biallelic disruption can cause male infertility through spermatogenic arrest at the spermatid stage. Funding was provided by the Bellux Society for Pediatric Endocrinology and Diabetology (BELSPEED) and supported by a Research Foundation Flanders (FWO) senior clinical investigator grant (E.D.B., 1802220N) and a Ghent University Hospital Special Research Fund grant (M.C., FIKO-IV institutional fund). The authors declare no conflict of interest. N/A.

Changing the work environment: The Clinical Scene Investigator Academy.

Changing the work environment: The Clinical Scene Investigator Academy.

Rett syndrome: The Natural History Study journey

AbstractUnderstanding clinical features and disease progression of Rett syndrome (RTT) and establishing clinical trial readiness was enhanced by the RTT Natural History Study (NHS). The NHS benefited from two key developments: one, the Orphan Drug Act passed by Congress in 1983 defining criteria for rare disorders in the United States and creating opportunities for pharmaceutical companies to develop products for individuals with rare disorders, and two, the Rare Diseases Act of 2002, which established the National Institutes of Health Office of Rare Diseases and provided research funding. Funding for the RTT and related disorders NHS was obtained in 2003, creating a broad network of experienced clinical investigators across the United States and producing critical results not only for RTT but also for related disorders: CDKL5 deficiency disorder, FOXG1 disorder, and MECP2 duplication syndrome. Longitudinal information from over 1800 participants (more than 1600 diagnosed with RTT) led to multiple reports describing their clinical features and natural progression and identified putative biomarkers and clinical outcome measures. Establishing clinical trial readiness assisted in evaluating the first FDA‐approved medication for RTT in 2023 and continues to provide opportunities to develop potentially life‐altering therapies. The experiences of the RTT NHS journey provide informative guidance for studying other rare neurological disorders. These lessons include positive features of developing productive collaborations focused on improving lives of people and families with RTT and related disorders, as well as lessons learned through retrospective analysis for improving overall conduct of natural history studies in rare disorders.

Formulation of a CITE metric for evaluating the clinical implications of medical studies and their originating hospitals in China.

The number of medical research publications by Chinese clinical investigators has risen substantially, contributing to 14.63% of the global total in 2019; however, their tangible impact on clinical decision-making remains limited. Various evaluation methods have been developed to measure hospital research competence in China, such as Fudan University's China hospital ranking and Science and Technology Evaluation Metrics (STEM) ranking, which predominantly focuses on factors such as academic reputation, volume of publications and patents, and research resources. However, composite indices may not fully capture the actual clinical value generated by medical research. To address this gap, we introduced the "Clinical Influence and Timeliness Evaluation (CITE)" metric to assess both the clinical importance of a given medical research study and the clinical influence of the hospital where it originated. The methodology used relies on the premise that influential medical research would be referenced in clinical guidelines, which serve as critical resources for clinicians. The CITE metric was applied for 78,636 medical studies concerning chronic obstructive pulmonary disease (COPD) published between 2000 and 2020 and referenced in both Chinese and international clinical guidelines for COPD. Specific indexes and formulas were derived to quantify the clinical weight of a medical research study (W) and its timeliness (T), enabling a dynamic assessment of the clinical value of each study and the overall contribution of a particular hospital. In this analysis, we incorporated 499 hospitals in China and quantitatively identified their dynamic clinical influence in COPD from 2000 to 2020. Our findings offer objective and targeted evaluation metrics by focusing on clinical relevance and recognizing the collaborative nature of medical research. The CITE metric provides an innovative method to gauge the true impact of medical research in China, with potential applications across different medical specialties. CITE can serve as a useful tool for understanding the relationship between research input and practical clinical outcomes, ultimately promoting more clinically relevant research endeavors.

New Pathways in Syphilis Vaccine Development.

The New Pathways in Syphilis Vaccine Development meeting was held prior to the start of the STI & HIV 2023 World Congress as a pre-meeting symposium to highlight recent advances in the development of an effective syphilis vaccine and discuss the challenges still faced by investigators. Internationally renowned public health officials, clinical investigators, and basic researchers from academia, government, and community-based organizations met on the 24 th of July 2023 in Chicago, Illinois. Four speakers discussed key research findings in syphilis vaccine development, which included antigen selection, identification of epitopes associated with protective immunity, and delivery platforms, with great emphasis on development of chimeric antigens. Significant progress was also shown on the elucidation of Treponema pallidum genomes from virtually all continents to assess the diversity in vaccine candidates of the syphilis spirochete.

Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). I. Drugs in preclinical and early clinical development.

For >30 years, the Eilat Conference on New Antiepileptic Drugs and Devices has provided a forum for the discussion of advances in the development of new therapies for seizures and epilepsy. The EILAT XVII conference took place in Madrid, Spain, on May 5-8, 2024. Participants included basic scientists and clinical investigators from industry and academia, other health care professionals, and representatives from lay organizations. We summarize in this article information on treatments in preclinical and in early clinical development discussed at the conference. These include AMT-260, a gene therapy designed to downregulate the expression of Glu2K subunits of kainate receptors, in development for the treatment of drug-resistant seizures associated with mesial temporal sclerosis; BHV-7000, a selective activator of heteromeric Kv7.2/7.3 potassium channels, in development for the treatment of focal epilepsy; ETX101, a recombinant adeno-associated virus serotype 9 designed to increase NaV1.1 channel density in inhibitory γ-aminobutyric acidergic (GABAergic) neurons, in development for the treatment of SCN1A-positive Dravet syndrome; GAO-3-02, a compound structurally related to synaptamide, which exerts antiseizure activity at least in part through an action on cannabinoid type 2 receptors; LRP-661, a structural analogue of cannabidiol, in development for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex; OV329, a selective inactivator of GABA aminotransferase, in development for the treatment of drug-resistant seizures; PRAX-628, a functionally selective potent sodium channel modulator with preference for the hyperexcitable state of sodium channels, in development for the treatment of focal seizures; RAP-219, a selective negative allosteric modulator of transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor regulatory protein γ-8, in development for the treatment of focal seizures; and rozanolixizumab, a humanized anti-neonatal Fc receptor monoclonal antibody, in development for the treatment of LGI1 autoimmune encephalitis. Treatments in more advanced development are summarized in Part II of this report.

Clinical Features, Investigative Profile and Association with Metabolic Syndrome in Facial Acanthosis Nigricans: A Case–Control Study in Indian Patients

Objectives: The present study was undertaken to study the clinical profile and laboratory abnormalities in patients with facial acanthosis nigricans (FANs). The significance of FAN as a marker of insulin resistance (IR), metabolic syndrome (MS) and its components was determined by comparing with controls without FAN. Materials and Methods: Fifty clinically diagnosed cases of FAN of all ages and both sexes were enrolled. Age- and sex-matched obese patients without FAN were included as controls. Waist circumference, blood pressure and body mass index were measured. Venous samples were taken from all patients and controls for measuring fasting glucose level, fasting insulin levels and fasting lipid profile. Statistical analysis was done using the Chi-square test and unpaired t-test. Results: The prevalence of hypertension, dysglycaemia, hyperlipidaemia, elevated Homeostatic Model Assessment for IR (HOMA-IR) and MS was significantly higher in cases of FAN than controls (P &lt; 0.05). The mean levels of fasting blood sugar, HOMA-IR, hypertension, high-density lipoprotein and serum triglycerides were significantly higher in patients of FAN than controls (P &lt; 0.05). The odds ratio for FAN cases developing MS was determined to be 5.31. Conclusion: FAN may be considered as a significant clinical marker of IR with increased risk for MS and its component when compared to controls. All patients with FAN should be considered for a thorough biochemical workup to rule out MS. In all detected cases, it is prudent to initiate prompt remedial measures including lifestyle changes and pharmacotherapy to prevent long-term morbidity and mortality.

Role of Optical Coherence Tomography (OCT), Fundus Photography, and Amsler Grid in Detection of Macular Disorders Associated with High Myopia

Abstract Background High myopia refers to ametropia characterized by elongation of optic axis and retinal and choroidal degeneration in the fundus, and high myopic patients present with various degrees of structural and functional retinal changes and thinning of the retinal thickness. Active screening for high myopic patients with imaging techniques by OCT, Fundus photography and amsler grid and providing patients with corresponding treatment on this basis may effectively reduce the risk of irreversible visual function damage. Objective To point to the importance of combining OCT, fundus photography with amsler grid testing in patients with high myopia. Methods This study was conducted on 40 eyes from EI-Demerdash Hospital outpatient clinic and ophthalmology department investigations unit in the period from June 2021 till May 2022; the patients were 24 females (60.0%) and 16 males (40.0%) with age ranged from 16 to 50 years. Results Our investigations gave us an idea about the macular diseases associated with high myopia and the importance of combining use of OCT, fundus imaging and amsler grid with patients with high myopia. These findings consist of chorioretinal atrophy, foveoschisis, choroidal neovascularization, dehiscence of retinal layers known as retinoschisis (foveoschisis or extre foveoschisis), macular holes (lamellar and full thickness), posterior retinal detachment. We can early detect theses changes in macula of highly myopic patients by Amsler grid testing as daily self monitoring and this can be useful in directing the patient to more sophisticated investigation tool like OCT and fundus photography and therefore give the patient the optimal chance to save the vision. Conclusion OCT combined with fundus photography and amsler grid testing are helpful tools that allow detailed evaluation of the macula in eyes with pathological myopia and easily anticipate, diagnose and follow up diseases associated with high myopia.

Ct2vl: A Robust Public Resource for Converting SARS-CoV-2 Ct Values to Viral Loads.

The amount of SARS-CoV-2 in a sample is often measured using Ct values. However, the same Ct value may correspond to different viral loads on different platforms and assays, making them difficult to compare from study to study. To address this problem, we developed ct2vl, a Python package that converts Ct values to viral loads for any RT-qPCR assay/platform. The method is novel in that it is based on determining the maximum PCR replication efficiency, as opposed to fitting a sigmoid (S-shaped) curve relating signal to cycle number. We calibrated ct2vl on two FDA-approved platforms and validated its performance using reference-standard material, including sensitivity analysis. We found that ct2vl-predicted viral loads were highly accurate across five orders of magnitude, with 1.6-fold median error (for comparison, viral loads in clinical samples vary over 10 orders of magnitude). The package has 100% test coverage. We describe installation and usage both from the Unix command-line and from interactive Python environments. ct2vl is freely available via the Python Package Index (PyPI). It facilitates conversion of Ct values to viral loads for clinical investigators, basic researchers, and test developers for any RT-qPCR platform. It thus facilitates comparison among the many quantitative studies of SARS-CoV-2 by helping render observations in a natural, universal unit of measure.

A new model to enhance enrollment of diverse participants to therapeutic clinical trials.

TPS1640 Background: Disparities in United States clinical trial participation are well described, with the inclusion of only 8% Black, 6% Asian, and 1% Hispanic participants in phase III oncology trials supporting US FDA filings in 2020. The FDA, Cancer Moonshot, and ASCO-ACCC have issued guidance, sponsored initiatives, and developed strategies to raise awareness around the importance of equality, diversity, and inclusion at centers with current clinical research capabilities. Centers with ongoing research capability are typically large academic or private practice sites located in urban areas. There is an urgent need to expand clinical trial offerings to rural communities as geographic constraints disproportionally limit people of color and people of low socioeconomic status from accessing innovative drugs offered only through clinical trials. An additional contributing factor to low enrollment of diverse participants is a lack of racial, ethnic, gender, and geographic diversity amongst clinical trial investigators, who may be more relatable and, thus, effective at recruiting underrepresented patients to clinical trials. Lastly, to provide high quality care for their patients, clinical investigators must have ability to identify and select trials which address the specific needs of the patients within their practice. We hypothesize that a tool which improves identification and inclusion of an expanded investigator pool will result in improved diversity of clinical trial participation. Methods: We have developed a bi-directional matching software program that allows healthcare providers to define their areas of interest and match them to available pharmaceutical company clinical trial opportunities. The software, Golgi-CONNECT, will be piloted with up to 500 oncology-focused healthcare providers across a diverse geographic landscape and up to 6 pharmaceutical companies of varying sizes to evaluate the functionality and usability of the application. Additionally, HCP-reported barriers to clinical trial conduct, inclusive of financial, infrastructure, training, mentoring and lack of support staff will be collected.

Enhancing Clinical Decision Support in Nephrology: Addressing Algorithmic Bias Through Artificial Intelligence Governance

There has been a steady rise in the use of clinical decision support (CDS) tools to guide Nephrology, as well as general clinical care. Through guidance set by federal agencies and concerns raised by clinical investigators, there has been an equal rise in understanding whether such tools exhibit algorithmic bias leading to unfairness. This has spurred the more fundamental question of whether sensitive variables such as race should be included in CDS tools. In order to properly answer this question, it is necessary to understand how algorithmic bias arises. We break down three sources of bias encountered when using electronic health record data to develop CDS tools: (1) use of proxy variables, (2) observability concerns and (3) underlying heterogeneity. We discuss how answering the question of whether to include sensitive variables like race often hinges more on qualitative considerations than on quantitative analysis, dependent on the function that the sensitive variable serves. Based on our experience with our own institution’s CDS governance group, we show how health system-based governance committees play a central role in guiding these difficult and important considerations. Ultimately, our goal is to foster a community practice of model development and governance teams that emphasizes consciousness about sensitive variables and prioritizes equity.

In memory of Professor Henry Wilde, MD, FACP: infectious disease physician, clinical and public health investigator, and educator.

In memory of Professor Henry Wilde, MD, FACP: infectious disease physician, clinical and public health investigator, and educator.

Hematology/oncology clinical investigator training: Is current model of education adequate?

9005 Background: Clinical investigator training (CIT) is commonly performed in an apprenticeship manner rather than following a prospective education model. This may lead to disparities in educational prospects. There is greater accesiblity for training opportunites prevailing in larger academic institutions – an advantage not always within reach for majority of oncology patients and professionals. Lack of predefined standard competencies during fellowship training may lead to significant heterogeneity, weaken the current pipeline, and decrease the number of principal investigators (PIs) for clinical trials. We performed a national needs assessment to understand oncology trainee and faculty perceptions of CIT. Methods: Program directors and leaders at 102 U.S. hematology/oncology (hem/onc) fellowship programs were contacted via email to invite their respective trainees and faculty to answer a 32-question cross-sectional survey. The study was IRB excempt. The survey was developed with the University of Chicago Survey Lab. Four thematic areas were interrogated: current level of experience in CI, knowledge of PI roles and responsibilities (R/R), areas of perceived weakness/lack of confidence related to CI, and interest in a course that teaches CI. Response frequencies and descriptive statistics were analyzed, with the goal of informing future targeted educational initiatives. Results: 207 respondents from 47/102 (46%) institutions completed the survey between 5/2023 – 11/2023. Respondents included 92 (40%) trainees and 137 (60%) attendings, 47% were men, 47% women and 57% had more than 9 years of experience as an attending post-speciality training. Among attendings, only 4.4% reported never participating in CIT, compared to 55.4% of trainees. Informal or “on the job” teaching was the most common method of learning PI R/R with response rate of 58% in attendings and 62% in trainees. Trainees reported lack of confidence and need for education in all aspects of CIT, and 85% indicated high level of interest in enrolling in a CIT course. Most attendings reported lack of confidence in areas of budget development (57%), quality of life (70%) and translational correlatives (51%). Others reported feeling weaknesses in designing primary and secondary end points (32%), letter of intent writing (33%) and creating protocols (31%). 53% of the attendings were interested in enrolling in a CIT course. Conclusions: To our knowledge, this is the first reported survey formally assessing current perceptions of preparedness in CIT within hem/onc in the U.S. Our findings strongly indicate that CIT educational gaps exist, even for attendings with prior CIT experience, and that training deficits are marked for trainees. A structured, practical, and widely-accessible CIT program is urgently needed to prepare the future hem/onc workforce. Acknowledgement: MERITS program and Section of Hem/Onc at University of Chicago.

Challenges and solutions to recruiting diverse populations to oncology clinical trials: A mixed-methods study of clinical research coordinators.

1619 Background: Multiple barriers limit the enrollment of diverse populations in oncology clinical trials (CTs). A review of our institutional CTs recruitment dashboard identified underrepresentation of Black and Latinx adults among thoracic and gastrointestinal (GI) oncology CTs participants compared to demographics of our catchment area and patient population. We conducted a mixed-methods study to identify barriers and potential solutions to the enrollment of diverse populations in oncology CTs in our institution. Methods: We conducted a mixed methods study enrolling clinical investigators and clinical research coordinators’ (CRCs) at an NCI-designated CCC in Northern California. Data from CRCs is presented. All CRCs supporting CTs in the thoracic and GI medical oncology were invited to participate in qualitative, one-on-one, semi-structured interviews. Participants completed 60-90 minutes interview and a short survey. Data were analyzed using a thematic inductive approach. Results: Of 14 CRCs, the majority were female (78.6%), with primary focus on thoracic (50.0%) and GI (35.7%) oncology CTs. 64.3% of CRCs reported &gt;80% of their work was dedicated to coordinating and managing therapeutic cancer CTs. In survey responses CRCs identified inability to take time away from work/family (64.3%), inadequate insurance coverage (42.9%), lack of transportation (35.7%), and language barriers (35.7%) as major barriers to enrollment of diverse patients in CTs. In qualitative interviews CRCs expressed the need of culturally and language appropriate materials for CT recruitment, establishing a sense of connection between clinical research staff/PI and patients, accommodating socioeconomic concerns, and resources to respond to potential participants’ mistrust of medical research. Main obstacles faced by CRCs during patient enrollment in CTs included lack of time, low patient awareness, resistance from colleagues, lack of multilingual staff, and inadequate logistical support. CRCs identified in-person interpretation as beneficial and identified a strong rapport between the clinical provider and the potential participant as the most important component to boost recruitment of minorities. Lastly, CRCs highlighted that institutional efforts are needed to increase CT participation among all populations. Conclusions: Lack of representation of diverse populations in CTs remains a complex challenge. Our study of CRCs’ perceptions highlights access to in-person translators, culturally and language concordant materials, education resources, and increased rapport as key areas for intervention to facilitate patient enrollment of diverse populations. Analysis into practice-specific patterns within our cancer centers can help identify areas for interventions to support the recruitment and enrollment of diverse populations in oncology CTs.