The ability to effectively lead an interdisciplinary translational team is a crucial component of team science success. Most KL2 Clinical Scholars have been members of scientific teams, but few have been team science leaders. There is a dearth of literature and outcome measures of effective Team Science Leadership in clinical and translational research. We focused our curriculum to emphasize Team Science Leadership, developed a list of Team Science Leadership competencies for translational investigators using a modified Delphi method, and incorporated the competencies into a quantitative evaluation survey. The survey is completed on entry and annually thereafter by the Scholar; the Scholar’s primary mentor and senior staff who educate and interact with the Scholar rate the Scholar at the end of each year. The program leaders and mentor review the results with each Scholar. The survey scales had high internal consistency and good factor structure. Overall ratings by mentors and senior staff were generally high, but ratings by Scholars tended to be lower, offering opportunities for discussion and career planning. Scholars rated the process favorably. A Team Science Leadership curriculum and periodic survey of attained competencies can inform individual career development and guide team science curriculum development.

Alcohol misuse among women has risen compared to men. Women experience barriers to engaging in patient-centered comparative effectiveness research (CER) that, in turn, limits the evidence base for addressing alcohol misuse in this population. In this manuscript, we describe WomenWise, a community-partnered project and outline how we co-developed community focused CER training curriculum and collaboratively planned future partnered learning sessions (PLSs) with Community Advisory Board (CAB) feedback. Through this approach we aim to empower women to contribute to future patient-centered CER and enhance the stakeholder capacity for future patient-centered research.

OBJECTIVES/GOALS: In this work investigating the epidemiological differences associated with Post Acute Sequelae of SARS-CoV-2(PASC) patho genesis we willassess the sex differences inocular viral persistence and the immunologic profile in tear film obtained from COVID-19 patients. METHODS/STUDY POPULATION: Participants will be enrolled from the NIH funded RECOVER Consortium at the 15 adult hubs in the US and will include those with acute COVID-19 (n=250), followed up at baselineto 48 weeks post infection. RT-PCR will be used to detect viral RNA and electro chemiluminescence assays will be used to detect IgG, IgA1 and IgA2 antibodies.Tear film antibody titers will be measured longitudinally in all participants to assess the kinetics of the immune responses in those who developed PASC and those who did not. Tear film antibody titers will be correlated with antibody titers in the blood and compared between those individuals with or without measurable viral RNA in tear film. RESULTS/ANTICIPATED RESULTS: Logistic regression models will be used assess the association of viral persistence with PASC status controlling for relevant covariates. Linear mixed regression models will be used to assess the association of IgA1/IgA2 with PASC status. We expect to observe delayed clearance of viral RNA and elevation in SARS-CoV-2 specific IgA2/IgA1 in the tear film of patients with PASC compared with those without PASC. Given evidence of increased PASC risk in women we expect to observe higher rates of SARS-CoV-2 ocular viral persistence and higher SARS-CoV-2 specific IgA2/IgA1 ratios in women with COVID-19 when compared to men with COVID-19. DISCUSSION/SIGNIFICANCE: There is concern that PASC will pose a major global health challenge given the scale of the Covid-19 pandemicand the patho genesis remains unclear. This work is highly likely to improve our understanding of the mechanisms of PASC and the reasons why women are more vulnerable to this condition.

Objectives/Goals: The operation of a clinical trials unit involves multifaceted tasks and stakeholders. A competent information system is critical to daily operations while ensuring smooth conduct of clinical research. We share 15 years of experience in the design and implementation of such a system at Mayo Clinic to inform other institutions with similar interests. Methods/Study Population: The Informatics team collaborated closely with nurse leaders and elicited input from additional stakeholders including nurse unit coordinators, lab managers, schedulers, investigators, study coordinators, and regulatory specialists throughout the phases of system design, development and continuous enhancements, and expansion. The stakeholders offered insights on the corresponding requirements throughout the study life cycle, from engaging with the study sponsor, operational review for protocol execution, development of study budgets, human subject protection and risk mitigation, data management and integration, to outcome monitoring, and regulatory reporting. The activities were then translated into functional components and implemented as a seamless and effective solution. Results/Anticipated Results: Patient safety, scientific rigor, operation automation, efficiency, and regulatory requirements were all considered in developing an integrated system, or the clinical research trials unit (CRTU) Tools. Our institution has leveraged the system for essential tasks from the study start-up, visit scheduling and execution, specimen collection and tracking, to individual protocol metrics and billing. We adopted a measure-as-we-go methodology so that data such as visit census, resource usage, and protocol deviation are tracked and collected during routine use of the system. Specifically, an issues/concerns/exceptions (ICE) tool is used for quality control and patient safety. Moreover, data quality greatly benefits from a task dictionary, standardizing the study activities that can be ordered and executed. Discussion/Significance of Impact: The implementation of a well-rounded clinical trials unit information system not only improves the operation efficiency and team productivity but also ensures scientific rigor and contributes to patient safety. We believe the experience can be informative to other institutions. More details will be shared in the poster.

Objectives/Goals: Create opportunities for early-stage research apprentices to obtain real-world knowledge expand float pool to meet unmet research staffing needs, and decrease investigator burden Increase operational efficiencies, decrease start-up time, establish metrics, and ensure transparency responsible fiscal stewardship to approach cost neutrality Methods/Study Population: The Research Coordinator Support Service (RCSS) is a pool of research staff available for hire on an hourly basis by Johns Hopkins University (JHU) investigators. RCSS consists of Apprentices we train on the job as well as Coordinators and Senior staff who have completed the apprenticeship program. Started in 2012, RCSS was placed under new management in November 2020. An expansion proposal was submitted to senior leadership for additional financial and human resources. After approval new systems were implemented and additional hires were made. Several efficiencies were introduced in start-up, study assignment, transparency, invoicing, and overall operations to address the waitlist of 25 studies. Senior leadership now required extensive metric reporting to evaluate program success. Results/Anticipated Results: To address the waitlist, current staff was redirected from purely educational to study-related activities and several new hires were made. The waitlist reduced steadily over time and more research occurred. Average hours of research support per month more than doubled from under 500 to over 1,000. When our Administrator left, we implemented an automated hours-based reporting and invoicing tool resulting in substantial cost-savings over rehiring the position. Apprentices, now with rapid onboarding and early study assignments are reporting high satisfaction and many have been promoted to Coordinator positions. Detailed spreadsheets with relevant metrics were created which are accessible, and regularly reported, to senior leadership for decisions on promotions and additional hires. Discussion/Significance of Impact: Budget belt-tightening requires organizations to reduce expenses while continuing to provide the essential services investigators need. This focus has caused RCSS to examine our program and add efficiencies. We hope others looking to build or expand their float pools will benefit from our experiences and the specific efficiencies we implemented.

OBJECTIVES/GOALS: Renal fibrosis is a critical pathophysiological event in chronic kidney diseases. Our goal is to determine the ability of dual-inhibitor of transforming growth factor beta receptor 1 (TGFα²R1) and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), TK850, on reducing kidney fibrosis. METHODS/STUDY POPULATION: To test the renal anti-fibrotic action ofdual TK850,8-10-week-old male and female C57BL/6mice with unilateral ureteral obstruction (UUO) induced kidney fibrosis were used. Mice were separated into 3 groups: group 1 contained mice that had UUO surgery (UUO control), group 2 contained mice prophylactically treated with TK850 thatstarted 7 days prior to UUO(UUO-P,20 mpk/d/ip), and group 3 contained mice interventionally treated with TK850 that started3 days after UUO(UUO-I,20 mpk/d/ip). Ten days following UUO the kidneys and blood were collected for analysis. Renal fibrosis was assessed from hydroxyproline content (measure of collagen)and histological collagen analysis using Picrosirius red stain. RESULTS/ANTICIPATED RESULTS: Renal hydroxyproline was increased equally in the UUO kidney of male (5.4 ± 0.41 µg/10mg, n=5) and female mice (5.5 ± 0.50 µg/10mg, n=5) compared to the contralateral control kidney (2.9 ± 0.14 µg/10mg, n=10). TK850 treatment in UUO-P mice (n=10, 3.4 ± 0.24 µg/10mg) and UUO-I mice (4.30 ± 0.20 µg/10mg, n=10) had significantly reduced hydroxyproline levels. Histopathological evaluation revealed that kidney injury increased collagen deposition in the UUO kidney (17.1 ± 0.43% collagen positive area, n=10) compared to the control kidney (2.0 ± 0.23%, n=10). TK850 treatment in UUO-P mice significantly attenuated collagen deposition (10.5 ± 0.38%, n=10), while UUO-I had significantly reduced collagen deposition as well (13.1 ± 0.25%, n=10). DISCUSSION/SIGNIFICANCE: Taken together, these results validate the dual TGFβR1/MAP4K4 inhibitor, TK850 as a potential therapeutic to mitigate renal fibrosis and supports the emergence of a combinational pharmacotherapeutic approach for multi-factorial kidney diseases.

Objectives/Goals: To identify clinical trial teams that are at risk of not meeting their recruitment goals as early in the recruitment period as possible, this project aims to provide timely accrual information and projected forecasts for accruals by the end of the recruitment period across all trials at USC. Methods/Study Population: This project aggregates recruitment accrual data periodically from OnCore to create per-study accrual pages that contain an up-to-date accrual chart, metrics like expected and actual accrual per month, and projected recruitment based on an X-month moving average (3 months by default). Trials at risk are identified as early as possible by using these projections to classify risk. In this initial phase, we’ve classified trials as medium risk (80%–99% accrual) or high risk (less than 80% accrual). The dashboard is currently available for all clinical trials at USC and users are automatically restricted to the studies that they administer or work on depending on their role. Results/Anticipated Results: The dashboard will provide visibility across the institution for the current accrual for all clinical trials in a standard, user-friendly format and use the same metrics and definitions of risk for trial accruals not meeting their targets. This will allow the institution to identify trials that need intervention to get back on track using a single set of criteria across all research teams. Users in different roles, whether department heads, principal investigators, or study coordinators can view the current accrual for all the trials that they administer or work on in one central location. The dashboard will also help to identify quality issues in OnCore by performing data quality checks nightly. Discussion/Significance of Impact: By providing a central location for role-based access to timely clinical trial accrual for the institution, the dashboard helps to identify trials at risk of not meeting their recruitment targets as early as possible to provide corrective advice/measures.

Traditional approaches for evaluating the impact of scientific research – mainly scholarship (i.e., publications, presentations) and grant funding – fail to capture the full extent of contributions that come from larger scientific initiatives. The Translational Science Benefits Model (TSBM) was developed to support more comprehensive evaluations of scientific endeavors, especially research designed to translate scientific discoveries into innovations in clinical or public health practice and policy-level changes. Here, we present the domains of the TSBM, including how it was expanded by researchers within the Implementation Science Centers in Cancer Control (ISC3) program supported by the National Cancer Institute. Next, we describe five studies supported by the Penn ISC3, each focused on testing implementation strategies informed by behavioral economics to reduce key practice gaps in the context of cancer care and identify how each study yields broader impacts consistent with TSBM domains. These indicators include Capacity Building, Methods Development (within the Implementation Field) and Rapid Cycle Approaches, implementing Software Technologies, and improving Health Care Delivery and Health Care Accessibility. The examples highlighted here can help guide other similar scientific initiatives to conceive and measure broader scientific impact to fully articulate the translation and effects of their work at the population level.

Early career researchers have unique demands, many of which contribute to increased stress, decreased professional fulfillment, and burnout. Consequently, academic institutions and government organizations, such as the National Institutes of Health, are beginning to embrace structured coaching as a tool to support physician wellbeing. To date, such coaching programs have demonstrated promising results, but little is known about whether early career research faculty find coaching feasible, accessible, or helpful. To explore this question further, we developed a novel group coaching intervention for clinician researchers and scientific faculty at the University of Texas Southwestern Medical Center based on the concept of appreciative inquiry, grounding the program in a positive and hopeful approach to the challenges faced by clinicians and researchers. Results from our program indicate this intervention is feasible, satisfactory, and helpful, with participants reporting enhanced self-reflection and empowerment. Effective for a wide array of research faculty, our program brought together diverse faculty, fostered connections, and encouraged future collaborations among this translational group. This suggests that our program provides a foundational blueprint that can be used by other academic medical centers who aim to develop group coaching efforts.

OBJECTIVES/GOALS: There is broad recognition that interdisciplinary research teams are uniquely suited to address complex research questions. At the Michigan Institute for Clinical & Health Research, we recognized a significant gap in support services at the University of Michigan for coordinating interdisciplinary teams to advance translational research. METHODS/STUDY POPULATION: The initial team science challenge we tackled was how to bring together cross-disciplinary groups, for the first time, to engage meaningfully and collaboratively with a ‘wicked’ problem of interest and create a shared vision. To address this, we developed Ideation Jams, which are facilitated experiences that help new groups build community, identify and prioritize research opportunities, determine how individual interests and other potential partners align with opportunities, and commit to next steps that will advance collaborative efforts. Ideation Jams leverage the methods and mindsets of design thinking, including divergence and convergence; making information visual; amplifying diversity; horizontal distribution of responsibility; and bias towards action. RESULTS/ANTICIPATED RESULTS: We have facilitated 11 Ideation Jams with 255 participants, including faculty, staff, health practitioners, and community members, who brought diverse expertise and insight to the research problems. Participant feedback has been overwhelmingly positive, with Ideation Jams fostering shared vision and innovation, and positively impacting various measures related to team performance. Participants have reported that Ideation Jams catalyzed various outcomes, including submission and award of grants, the introduction of new and specialized clinical offerings, and development of an interdisciplinary research agenda for their field of interest. Most recently, we trained representatives from five Clinical & Translational Science Award hubs to implement Ideation Jams at their universities. DISCUSSION/SIGNIFICANCE: Ideation Jams are ideal for mobilizing new groups around complex research problems, moving them from blue-sky thinking to action planning in three hours. Ideation Jams will be integrated into a suite of facilitated experiences, trainings, and grant development services to provide iterative support as teams advance their research priorities.

Objectives/Goals: Collaborations between Academic Medical Centers (AMCs) and Historically Black Colleges & Universities (HBCUs) are critical to addressing health disparities and building research capacity. Herein, we examine the Duke-NCCU Collaborative Translational Research pilot funding program [2018–2023] to identify opportunities, challenges, and lessons learned from querying key stakeholders. Methods/Study Population: The Duke-NCCU collaborative pilot funding program was launched to support new inter-institutional collaborations that aim to accelerate research discoveries into testing in clinical or population settings. Eight one-year, $50,000 collaborative grants were awarded. Each funded team was assigned a CTSI Project Leader (PL) for project management support. To evaluate the program, we developed surveys targeting principal investigators (PI) and PLs. Questions covered collaboration motivation, goals, outcomes, operational processes, project management support, institutional differences, and challenges. Qualitative analysis will be employed to evaluate the responses and identify common themes. Results/Anticipated Results: The PI survey examines aspects of inter-institutional collaborations, focusing on common themes, such as authorship, definition of success, and institutional culture. The PL survey prompts feedback on managing inter-institutional teams, expectations, and challenges. Select questions were shared between both surveys to capture both perspectives. Surveys were reviewed by members of the Duke CTSI evaluation and team science teams. The PI survey will be disseminated to 16 investigators, while the PL survey will reach 5 project leaders. Built on Qualtrics, each survey takes 20–30 minutes to complete. To encourage participation, incentives will be offered as two $100 gift card drawings. Respondents can choose to complete the survey on Qualtrics or through a recorded and transcribed Zoom session. Discussion/Significance of Impact: AMC-HBCU inter-institutional collaborations drive innovation, workforce development, and equitable dissemination of outcomes. This study exemplifies collaboration, offering insights into translational research collaborations critical to advance equitable healthcare and improving population health.

Objectives/Goals: In January 2023, Mayo Clinic set a goal to have 10% of studies open for six months or more without accrual. At that time, Mayo Clinic Florida had 19% non-accruing studies and 18% non-accruing clinical trials. Research administration implemented strategies to improve accrual outcomes. Methods/Study Population: Two strategies were developed to address non-accruing trials: a clean-up approach and a proactive approach. The clean-up approach involves escalating studies that haven’t been enrolled in over 6 months, identifying barriers, and escalating communication with the principal investigator (PI) and research administration alongside a physician partner. The proactive approach targets studies at the 3-month mark to address issues before reaching 6 months without accrual. Both strategies aim to reduce the cost and effort of non-accruing studies by either creating an enrollment plan or closing the study. Results/Anticipated Results: Since implementation, Mayo Clinic Florida’s non-accruing study portfolio decreased by 10%, and its clinical trials non-accruing portfolio decreased by 7% as of October 2024. Research Administration tracks key metrics (reasons for no enrollment, justifications, and actions) to identify trends and mitigate future accrual risks. A REDCap electronic data capture tool hosted at Mayo Clinic (supported by CCaTS grant UL1TR002377)1 notifies principal investigators when their studies are non-accruing. Future plans include establishing an API with Mayo Clinic’s portfolio management system to streamline the process while maintaining awareness and collaboration. Discussion/Significance of Impact: Through increased monitoring, enhanced communication, and deeper collaboration, Mayo Clinic Florida effectively reduced non-accruing studies in its research portfolio. This approach minimizes effort and costs associated with under-enrolled studies while tracking key metrics to inform future study development.

OBJECTIVES/GOALS: The goals of the present study were to examine levels and potential changes in oxytocin and HPL over the course of pregnancy. We assessed the potential predictive value of oxytocin and HPL on maternal-fetal attachment, anxiety and depression at three timepoints during pregnancy. METHODS/STUDY POPULATION: Pregnant women (n=70) enrolled in a longitudinal, rolling protocol study. Eligibility criteria included 1) singleton pregnancy confirmed at early pregnancy screen (EPS) ultrasonography, 2) mother aged 19 or greater, and 3) fluent in English. Predictors (oxytocin and HPL levels) were measured via blood draws at the same three times (early-stage, mid-stage, and late-stage) that MFA, anxiety and depression questionnaires were completed. RESULTS/ANTICIPATED RESULTS: An increased OT level compared to a mother’s average OT level did not have a statistically significant effect on MFA (within-person estimate = 0.02, 95% CI: -0.03 to 0.05, p = 0.427. An increased HPL level compared to a patient’s average HPL level did not have a statistically significant effect on MFA (within-person estimate = -0.10, 95% CI: -0.67 to 0.47, p = 0.730). The main effect of between-person HPL was significant; such that a one-unit increase in average HPL level was associated with a 0.52 higher anxiety score (between-person 95% CI: 0.08 to 0.96, p = 0.022). The main effect of between-person HPL was significant, such that an increased average HPL level was associated with a 0.45 higher depression score (between-person estimate = 0.45, 95% CI: 0.04 to 0.86, p=0.031). DISCUSSION/SIGNIFICANCE: To our knowledge, our study is the first to measure HPL and MFA over the course of a pregnancy. At this point, perhaps the best we can say is that HPL is a promising new target hormone that may be related to psychological symptoms surrounding pregnancy.

OBJECTIVES/GOALS: Healthcare sectors are rushing to develop AI models. Yet, a dearth of coordinated practices leaves many teams struggling to implement models into practice. The Enterprise AI Translation Advisory Board uses across-disciplinary team to facilitate AI translation. METHODS/STUDY POPULATION: The Mayo Clinic Enterprise AI Translation Advisory Board was established to assess AI solutions lever aging cross-disciplinary team science to accelerate AI innovation and translation. The 23-member board reflects expertise in data science, qualitative research, user experience, IT, human factors, informatics, regulatory compliance,ethics, and clinical care, with members spanning thought leadership, decision-making, and clinical practice. Taking an approach of respectful communication, transparency, scientific debate, and open discussion, the Board has consulted onover two dozen projects at various stages of the AI life cycle. RESULTS/ANTICIPATED RESULTS: Common issues identified for projects earlier in the AI life cycle, sometimes fatal but often address able once identified, include a lack of buy-in from potential product users, a lack of planningabout integration into clinical workflow, inadequately labeled data, and attempting to use machine learning when what is desired is really a causal model for intervening. Recommendations for projects later in the AI life cycle include details of a testing plan (silent evaluation, pragmatic clinical trials), advice about clinical integration, both post-hoc and on going auditing for performance disparities, and planning for regulatory clearance. DISCUSSION/SIGNIFICANCE: Advising is more valuable for projects at the ideation phase, when multi disciplinary interrogation can identify weaknesses. But at all phases, projects have gaps related to a lack of specific disciplinary expertise. A multi disciplinary cluster like the AI Translation Advisory Board seeks to address these gaps.

Objectives/Goals: Historically, the Univ. of Missouri (MU) Sch. of Medicine (SOM) is known for its strong clinical and education programs. In 2020, MU recruited an Executive Vice Chancellor (EVC) for Health Affairs and subsequently Dean of the SOM who initiated programmatic steps to develop and establish a centralized clinical and translational research (CTR) infrastructure. Methods/Study Population: In order to develop and establish a CTR infrastructure, the EVC/Dean of the SOM created and recruited to the combined position of the Associate Dean (AD) for CTR and Associate Director (ADR) of clinical research (CR) for the Ellis Fischel Cancer Ctr. (EFCC) in 2021. The AD CTR was appointed the Chair of the Clinical and Translational Science Unit (CTSU) Steering Committee with the charge of establishing a 10,000 sq. ft. CTSU to be housed in the newly built $225M Roy Blunt NextGen Precision Health Bldg. and for re-building the Clinical Trials Support Office (CTSO), and the Clinical Trials Office (CTO) at the EFCC in his other role as the ADR CR. The AD CTR was also charged with implementing the OnCore clinical trial management system (CTMS) to centrally track and fiscally manage SOM clinical trials. Results/Anticipated Results: Between 2021 and 2023, a CTR infrastructure was developed and established at the MU SOM. A total of 25 new clinical research staff (CRS) and leadership were hired that included a Sr. Dir. of CR Operations, clinical research nurses (CRNs) and coordinators (CRCs), Regulatory/Data/Fiscal/Project/Compliance/Coverage Analysis Coordinators between the CTSU/CTSO and the CTO of the EFCC. The CTSU was built with 10 FTE CRS [CRNs  =  5, CRCs  =  2, administrative staff  =  2, Sr. Lab. Tech.  =  1, and a manager]; the CTSO was re-built with 9 FTE CRS [Fiscal (n = 3), Project (n = 2), Compliance (n = 2), Coverage Analysis (n = 1) and Recruitment (n = 1) coordinators]. The EFCC CTO was re-built with 8 FTE CRS [CRNs  =  4, Fiscal (n = 1), Data (n = 1) & Regulatory (n = 2) coordinators]. The implementation of the OnCore CTMS tracking function was also completed. Discussion/Significance of Impact: Overall, the development and establishment of the CTR infrastructure has led to a significant increase and enhancement (e.g., capacity) to conduct clinical trials at the MU SOM. For example, this has led to a significant increase in the average annual enrollment to interventional oncology clinical trials [n = 82 (2021–2023) vs. n = 42 (2016–2020), p = 0.004].

Few studies have explored the challenges that the COVID-19 pandemic has presented for Clinical Research Units (CRUs), the solutions that have been implemented, and the changes that have been made in the operational guidelines for these entities. This study sought to identify and document common practices implemented by CRUs around the United States of America (USA) when addressing the unique challenges posed by the COVID-19 pandemic. This descriptive study utilized a non-experimental mixed-methods approach and gathered data from representatives of 43 CRUs across the USA. An online survey was followed by in-depth interviews. The findings show that challenges faced from the COVID-19 pandemic, changes made to daily operations, and lessons learned are very similar across CRUs. Although most CRUs never stopped performing essential clinical research, many adapted to the pandemic by engaging in virtual visits, and many played key roles in administering and supporting both COVID-19 therapeutic and vaccine trials. Follow-up interviews showed that processes for formal approval and reopening were similar across CRUs. In addition to highlighting the significance of the role played by CRUs during the COVID-19 pandemic, this study addresses the relevance of CRUs and lays the groundwork for future conversations on the importance of these units.