Objectives/Goals: Lack of comparative data limits research operations quality improvement (QI). The Northwest Participant and Clinical Interactions (NW PCI) Network, a group of 17 unaffiliated university and health system-based research centers, built an operations dashboard to track efficiency and enable multisite QI projects. Methods/Study Population: A Data Governance Working Group was assembled to establish shared data governance, draft nondisclosure (NDA), and data transfer and use agreements (DTUA) suitable across organizations and standardize research operations metric definitions. Sites in the NW PCI Network were recruited to participate in a pilot program to assess data sharing and governance infrastructure, data collection, upload procedures, and data visualization tools. The NW PCI Coordinating Center developed an analytical data dashboard of research operations metrics and conducted semi-structured interviews with participating sites to understand barriers and facilitators of program success. Results/Anticipated Results: Four sites (2 health systems, 2 universities) were recruited for the pilot and reviewed and executed NDAs and DTUAs. Three of the sites have submitted data for a total of 1,405 studies. Of the 24 requested data operations metrics (e.g., study startup, recruitment, implementation, and basic study information), 71% of the metrics were submitted by all three sites (n = 17), 25% were submitted by at least one site (n = 6), and 4% were not submitted by any site (n = 1). Interviews with sites after data submission found areas for improvements (clarification of data definitions, efficiency of data upload process) and positive effects for sites (e.g., process improved insight into own data operations). Discussion/Significance of Impact: Unaffiliated research centers created data governance procedures to enable sharing of operations data. Pilot sites successfully loaded most but not all operations data to the dashboard. Interviews identified process limitations and opportunities for improvement to inform expansion to all NW PCI sites.

OBJECTIVES/GOALS: To present Substance Abuse Research: Bench to Community (SARB2C) as a model for team science both within and between institutions. Emerging from targeted efforts by the NIH to engage translational scientists in prominent public health issues, the initiative illustrates the benefits of bringing together researchers and trainees to share ideas. METHODS/STUDY POPULATION: In 2019 a group was formed at University of Florida to discuss ongoing translational research in the area of substance abuse, including faculty, staff, and trainees from across the campus. The group was expanded in February 2022 to include domestic colleagues at the University of Kentucky as well as international collaborators at Chulalongkorn University in Bangkok, Thailand. One-hour monthly meetings began in person but now take place virtually. Larger projects are discussed individually, focusing on opportunities for collaboration. Attendees also provide updates on their work, including proposals in development and manuscripts in process. This facilitates dialogue around the science, from the bench to the community, and connects people to advance team science. RESULTS/ANTICIPATED RESULTS: In light of the ongoing opioid epidemic and the public health threat of other emerging substances, collaboration among researchers in this area is essential to advance the science and explore real-world solutions. SARB2C demonstrates the benefit of connecting researchers across T0 to T4, and that of including trainees for invaluable experience. This environment fosters open discussion and creativity and helps break down the silos that impede science. A highlight from early in the group’s history was a visit from the Program Officer for the UF Clinical and Translational Science Institute in February 2020. Since that time, multiple collaborations have resulted in grants submitted, such as P30 center grants and an innovative R61/R33, as well as numerous publications. DISCUSSION/SIGNIFICANCE: A complex public health emergency like the opioid epidemic requires creativity and collaboration, from laboratory science to interventions in the community, putting it squarely within the sights of translational research. SARB2C will soon enter its fifth year of linking researchers and training the next generation of scientists.

Mentorship is a vital part of the training provided in the K and T programs funded by the Clinical and Translational Science Awards (CTSA). However, the inputs, indicators, and outcomes associated with a successful mentoring relationship remain poorly understood. In this review, we critically examine the current body of literature on mentorship in a CTSA context. We conducted a comprehensive search of the literature for relevant research articles. We included articles that were contextualized within a CTSA hub, examined a mentorship program, and conducted evaluation research. Through an initial search of online databases and by reviewing reference sections of relevant articles, we identified 141 potentially relevant articles. Twenty-five of these articles met our inclusion criteria. We identified three categories of research: nationwide institutional surveys of CTSA mentorship programs, mentored research training programs, and mentor training programs. While the findings highlighted the effectiveness of mentor training and mentored training programs, there is a notable lack of assessment of mentoring inputs and indicators. Based on our review, we propose a model for the evaluation of CTSA mentorship that includes measurable inputs, indicators, and outcomes. This model provides a holistic framework for evaluators and CTSA program directors to better understand their mentorship programs.

In a prospective, remote natural history study of 277 individuals with (60) and genetically at risk for (217) Parkinson’s disease (PD), we examined interest in the return of individual research results (IRRs) and compared characteristics of those who opted for versus against the return of IRRs. Most (n = 180, 65%) requested sharing of IRRs with either a primary care provider, neurologist, or themselves. Among individuals without PD, those who requested sharing of IRRs with a clinician reported more motor symptoms than those who did not request any sharing (mean (SD) 2.2 (4.0) versus 0.7 (1.5)). Participant interest in the return of IRRs is strong.

OBJECTIVES/GOALS: A barrier to the proliferation of team science is that academicians are often trained in disciplinary silos where “independent” research contributions are lauded. To tackle some of the most pressing scientific challenges, dismantling silos and increasing team science training efforts that focus on early career investigators is a must. METHODS/STUDY POPULATION: A team science training workshop for early career investigators from varied disciplinary backgrounds was informed by a 20-item needs assessment that addressed essential team science competencies and was completed by early career investigators participating in federally funded professional development programs on our campus. During the workshop, the benefits of cross-disciplinary teaming was discussed. Strategies including team formation, team effectiveness and/or dysfunction, diagnosing team strengths and weaknesses, and teaming in community settings were discussed. Instructional methods included short presentations, video clips, case studies, group discussions, pair and share activities, and panel discussions with expert role models encouraged active learning. RESULTS/ANTICIPATED RESULTS: The impact and value of the workshop series to participant’s professional development and knowledge of team science concepts will be evaluated before and after the workshop. Multiple Likert-scale items focused on team science competencies (e.g., confidence in your ability to carry out responsibilities specific to your role on a team, recognize when the team is not functioning well; engage team science practices in on-going research), and open-ended questions (e.g., importance of engaging community partners in academic research teams, vision of what factors contribute to an effective team science collaboration) will be completed by program participants before and after completing the workshop. DISCUSSION/SIGNIFICANCE: Effective collaboration among scientists with expertise in different disciplines is needed to address and solve complex scientific problems. We believe our interactive approach to team competency training sessions would work in a variety of settings and improve team skills.

OBJECTIVES/GOALS: Since 2017, we have used the Design Lab methodology to support investigators taking innovative approaches to clinical effectiveness trial design. To date we have held 12 Design Labs and this year we are creating a handbook that will support dissemination of this approach across the Clinical and Translational Science Award consortium. METHODS/STUDY POPULATION: The Clinical Trial Design Lab brings together a multi-stakeholder group to consider innovative and impactful clinical trial designs. An investigative team is selected from a competitive pool of applicants, after which expert-led consultations support the investigator team to think about evidence generation in the context of the full treatment development pathway. Teams map the stakeholders at each step of this pathway (e.g. clinicians, patients, researchers, funders, industry experts, policy experts, regulatory experts, payers) and consider innovative design solutions. These consultations prepare investigators for an event that involves all stakeholders in a structured and facilitated discussion about trial designs that generate the best evidence and increase potential for health impact. RESULTS/ANTICIPATED RESULTS: The result of our work will be a set of Design Lab principles, a handbook with templates that support stakeholder mapping and structured discussions, and educational resources to accompany the handbook. The work is supported by a literature review that characterizes the multi-component processes included in the Design Lab, situates them within the larger context of team science interventions, and lays groundwork for the development of process metrics and impact evaluation criteria to assess the Design Lab method. In this poster presentation, we will share our multi-component broadly engaged team science approach, provide a brief outline of the principles and educational resources, and include an early version of the evaluation criteria. DISCUSSION/SIGNIFICANCE: Broadly engaged team science supports innovative thinking about study design and is especially important in the development of clinical trials. We have grown the Design Lab program of work over the past seven years and are now able to characterize our team science methodology and support others to use this approach to innovate for health impact.

Objectives/Goals: Translational researchers often struggle to navigate a complex constellation of institutional resources spanning the IRB to bioinformatics units. We had two aims 1) Systematically map all institution-wide research support units and 2) leverage this database within a generative AI virtual concierge tailored to local investigator queries and needs. Methods/Study Population: This study leveraged mixed methods approach. First, we conducted needs assessments of local study teams to identify barriers to translation, revealing that research resources are often unknown to study teams. Second, we identified all investigators, institutional units, and offices offering such resources that we call research support units (RSUs). RSUs were surveyed, collecting contact information (leadership, website, physical location), services provided, type of research supported, and performance metrics. Third, the resource database was integrated into a large language model (LLM, e.g., ChatGPT4o) using a retrieval augmented generation (RAG) system within an R Shiny application called virtual concierge. Queries and responses are recorded for quality improvement. Results/Anticipated Results: Needs assessment focus groups consisted of clinical and basic science investigators, study team members (e.g., clinical research assistants), core directors, and administrators (n = 26). Six sessions were conducted in Spring 2024. A major resultant theme was difficulty finding RSUs “by trial and error” and lacking a “clear defined pathway” for accessing RSUs. This prompted a survey-based environmental scan to identify institutional research resources. There were 122 diverse RSUs ranging from the IRB, to grant writing, to single cell sequencing. Each research unit offered a median of 6 service types, totaling 410 service types overall. The resultant Virtual Concierge meaningfully responds to investigator resource queries with appropriate contact and access information. Usability testing is underway. Discussion/Significance of Impact: Linking researchers with translational resources requires mutual understanding, timely communication, and coordination across teams. We systematically filled these information gaps between investigators and institutional resources. Our Virtual Concierge AI bot can help researchers navigate resources through the translational process.

Objectives/Goals: Mayo Clinic Florida’s Clinical Research Units develop over 200 clinical studies on average annually. Almost 30% of these projects are developed and then are unable to activate due to a variety of operational factors. To increase the success rate, a scoring tool was created to assess the risk associated with the development of these research projects. Methods/Study Population: A project team comprised of members of research administration and physician leadership developed a rapid project management (RPM) scoring tool to assess operational risk factors. The scoring algorithm was embedded into an existing REDCap database, using a combination of identified variables and calculated fields. All noncancer industry sponsor-initiated clinical studies were scored at intake. According to the following categories: enrollment timelines, study team capacity, and previous experience with the Sponsor. Studies with a score greater than the established threshold were referred to physician leadership for transparent discussions with the principal investigator regarding the identified study development-related risks. Results/Anticipated Results: The RPM tool has assessed close to 200 projects since implementation in June 2022. An interim analysis is being conducted of all projects assessed by the RPM tool dating from implementation to May 2024 to compare the outcomes of these studies with the given RPM score. We anticipate based on anecdotal evidence gathered during the course of this pilot project that the RPM tool will show a correlation between risks identified and study outcomes as defined as successful activation of trials, or rationale of project development failures. We anticipate a reduction in the amount of time elapsed and effort expended developing projects with scores reflecting identified project development-related risk factors. Discussion/Significance of Impact: The RPM tool provides an opportunity to allocate resources to studies with the greatest potential for successful activation. In the future, the RPM tool may be used to identify risk factors associated with enrollment and accrual of participants.

OBJECTIVES/GOALS: Maternal opioid use disorder (OUD) is linked to poor fetal outcomes. While it has been established that opioids can cross from maternal to fetal circulation, the mechanisms underlying these adverse outcomes remain poorly defined. This study aims to uncover OUD-associated immunological changes in maternal and fetal circulation. METHODS/STUDY POPULATION: To study the effect of maternal OUD on the maternal immune system at delivery, we collected maternal blood samples at delivery from healthy pregnant women (controls) and pregnant women with a diagnosis of severe OUD. To study the impact of maternal OUD on newborn immunity, we also collected umbilical cord blood (UCB) at delivery. Flow cytometry was used to determine the frequency and phenotype of circulating immune cell subsets and responses to stimulation. Isolated monocytes were stimulated with bacterial/viral agonist cocktails, while T and NK cells were stimulated with PMA/ionomycin. The impact of maternal OUD on circulating immune mediators was determined by Luminex and on monocyte activation markers sCD14 and CRP by ELISA. RESULTS/ANTICIPATED RESULTS: In maternal circulation, OUD was associated with a significant decrease in markers of inflammation, cell proliferation, and activation. Frequencies of immune cell subsets were impacted by OUD, shown by an expansion of CD8+ EMRA T cells, marginal-zone B cells, mDCs, non-classical monocytes, and CD16low NK cells. While no differences were seen in T and NK cell responses to stimulation, monocytes and pDCs had significantly lower responses to bacterial and viral agonist stimulation. Analysis of UCB revealed increased levels of pro-apoptotic/T cell exhaustion mediators and pro-inflammatory cytokines, albeit decreased levels of several chemokines and growth factors. The UCB immune landscape is altered with maternal OUD, as demonstrated by a shift from naive to memory CD8+ T cells and a decrease in pDC frequency. DISCUSSION/SIGNIFICANCE: OUD dampens maternal peripheral immunity, possibly contributing to poor placental function or premature/delayed labor. Monocytes and pDCs lack antimicrobial functionality, suggesting increased infection susceptibility with OUD. Finally, these implications extend to the fetal compartment, shown by heightened immune activation in UCB.

Objectives/Goals: Mayo Clinic’s Clinical Trials Beyond Walls™ (CTBW) program collaborates with study teams to implement decentralized elements in clinical trials, enabling participation from home or local settings. In cancer treatment trials, traditional paper pill diaries are replaced with real-time digital tracking solutions to monitor chemotherapy adherence. Methods/Study Population: The CTBW team developed a solution to deliver electronic pill diaries to research participants using the electronic health record (EHR) system Epic and patient portal MyChart1. The solution includes a portal message to remind participants to take chemotherapy. Medication dose, date taken, and reasons for missed doses (e.g., “I forgot” or “side effects were bothersome”) are captured. An automated in-basket notification system alerts the study team when predefined conditions are met. Configurable medication schedules ensure diaries are sent according to the prescribed frequency. Reports were generated to allow study teams to monitor all participant diaries. Results/Anticipated Results: The CTBW team implemented this digital pill diary in neuro-oncology trial NCT066250472. We anticipate the pill diary in the patient portal will enhance chemotherapy adherence by capturing real-time data in a platform widely used by Mayo Clinic patients. This patient-reported data is stored in the EHR, where it is accessible to providers and study teams. This allows for continuous monitoring, which facilitates a streamlined review of potential adverse events, improved compliance visibility, and timely treatment adjustments compared to paper-based or external solutions. The system also streamlines data entry, reducing human error and eliminating manual transcription. The created language and workflow templates allow the CTBW to scale this approach to future cancer trials Discussion/Significance of Impact: Decentralized clinical trial participants may never visit Mayo Clinic, making digital recording essential. The EHR-based digital pill diary enables continuous monitoring within a familiar system for providers and patients, increasing study team visibility, and allowing for earlier intervention in cases of non-compliance or adverse events.

Infants with congenital heart disease (CHD) may have impaired cerebral autoregulation (CA) associated with cerebral fractional tissue oxygen extraction (FTOE). We conducted a pilot study in nine CHD neonates to validate a noninvasive CA measure, cerebrovascular stability index (CSI), by eliciting responses to postural tilts. We compared CSI to an invasive measure of CA and to FTOE collected during tilts (FTOESpot). FTOESpot correlated with CSI, as did the change in FTOE during tilts, but CSI’s correlation with impaired CA did not reach significance. Larger trials are indicated to validate CSI, allowing for noninvasive CA measurements and measurements in outpatient settings.

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.