Clinical trials conducted with incarcerated populations are rare. We present a case example of one such jail-based cancer prevention clinical trial to demonstrate the importance of including a theory-driven approach to intervention framing, novel experimental designs to boost access to low-risk trials, and retention strategies for long-term follow-up of hard-to-reach populations. As such we offer a social determinant of health framework to ensure cancer prevention research is conducted through the lenses of health promotion and health equity. Deviations from the gold-standard randomized control design, transparent systematic allotment, and street-based outreach retention strategies contribute to the feasibility of conducting clinical trials in carceral settings and after people leave jail. Best practices presented can be used in design and conduct of future clinical trials with criminal legal system-involved populations.

Objectives/Goals: Clinical and Translational Science Award hubs will be the primary investors in advancing translational science until academic reward structures and funding agencies incentivize these efforts. As such, hubs will benefit from systematic methods to strategically identify and efficiently solve challenges in the translational process. Methods/Study Population: Translational science (TS) problems are abundant, complex and typically reside within systems of interconnected processes and people. These characteristics are informing efforts at the Michigan Institute for Clinical & Health Research (MICHR) to create a framework that guides how we select the right translational science problems to invest in solving and how we solve these problems in user-centric, efficient, and effective ways. Our framework leverages methods from the fields of design and systems thinking. Design thinking is a human-centered approach to problem solving and innovation that is ideal for tackling ill-defined and complex problems. Systems thinking methods help us situate and analyze problems within broader dynamics, structures, and perspectives, ultimately informing key levers for change. Results/Anticipated Results: Applying design and systems methods, we created an eight-step TS framework that centers on the diverse perspectives of those experiencing a TS problem and those implementing solutions. The first four steps guide in defining the TS problem within its context, understanding why previous solutions have not worked, and determining the value and generalizable knowledge that a solution would create. The last four steps are solutions-focused, with iterative brainstorming, testing, and refining of potential solutions before they are implemented locally and disseminated widely. Each step is underpinned by guiding questions, methods, outputs, and metrics to ensure a scientifically rigorous approach to defining, prioritizing, and solving TS problems. We are currently prototyping the framework with various case studies. Discussion/Significance of Impact: A framework that guides strategic investment in TS should ensure resources are allocated to the most well-defined and pressing problems that are important to the community and should speed up the process of creating solutions. Engaging myriad viewpoints leads to more viable solutions that foster a commitment to real change within the research ecosystem.

OBJECTIVES/GOALS: In the U.S., over 4 million people including children experience transient periods of undernutrition annually. Cardio-metabolic and renal diseases are more prevalent in this population. We are investigating therapeutic strategies to reverse the long-term risk of these diseases in a rat model of transient undernutrition followed by refeeding. METHODS/STUDY POPULATION: Thirty six female Fischer rats (3-months of age) were initially divided into 2 groups. Half were fed regular chow (CT) while the other half were severely food restricted (sFR) by 60% from 0-2 weeks (wks) followed by refeeding from 2-14 wks (sFR-Refed). These 2 groups were then subdivided and treated ± metformin (Met) from wk 7 to wk 12 (n=9/group). High precision ultrasound was conducted on live rats to assess heart and kidney function immediately after the sFR period ended (wk 2) and at the end of the study (wk 14). At the conclusion of the experiment, the rats were sacrificed and the histology of the kidney and heart tissues were analyzed in hematoxylin and eosin-stained sections. The protein to DNA ratio was also calculated in homogenates from these tissues. RESULTS/ANTICIPATED RESULTS: In sFR-Refed rats, cardiac output (CO), heart rate (HR) and renal artery blood flow (RBF) were decreased by 11 ± 1.5%#, 7.0 ± 6.0% and 22 ± 0.6%#, respectively, compared to control (CT) rats; #p<0.05. Mean glomerular diameter was reduced in the kidneys of sFR-refed rats compared to CT and this effect was attenuated by metformin treatment [(µm): CT, 406 ± 31; sFR-Refed, 383 ± 11, p<0.06; CT+Met, 393 ± 18; sFR-Refed+Met, 407 ± 18*]. Furthermore, the mean cardiomyocyte thickness was reduced in sFR-Refed rats compared to controls while metformin treatment prevented this effect [(µm): CT, 16.4 ± 3.6; sFR-Refed, 11.5 ± 2.3#; CT+Met, 16.4 ± 3.6; sFR-Refed+Met, 15.9 ± 3.2*]. #p<0.05 vs. CT, same treatment; *p<0.05 vs. Met, same diet; two-way ANOVA. DISCUSSION/SIGNIFICANCE: These findings have promising implications for metformin use to mitigate long-term impairments in heart and kidney structure and function in individuals who have experienced bouts of undernutrition earlier in life for either voluntarily (e.g., very low calorie dieting) or involuntary (e.g., very low food security) reasons.

OBJECTIVES/GOALS: Cognitive decline is associated with obesity, stress, poor sleep, and circadian rhythm misalignment, which are themselves functionally intertwined. Irregular food intake timing exacerbates these all. Prolonged nightly fasting (PNF) aligns food intake with innate circadian rhythms. METHODS/STUDY POPULATION: A nationwide, remotely-delivered, 2-arm randomized controlled trial was conducted to assess feasibility and 8-week outcomes of cognition, stress, sleep, eating behaviors, and general eating habits, after a PNF intervention (14-hr nightly fast, 6 nights/week, no calories after 8pm) compared to a health education control (HEC) condition. Eligible participants were living with obesity, stress (Perceived stress scale-4 (PSS-4) total score ≥5), and memory “not as good as it used to be.” Data were collected via Zoom meetings with participants and trained staff and entered into REDCap. All participants had weekly staff check-in calls to report fasting times (PNF group only) and feedback. RESULTS/ANTICIPATED RESULTS: Eligible participants were enrolled from 37 of 50 US states; N=58, 86% women, 71% white, 93% non-Latinx, mean (SD) 50.1 (5.1) years of age, BMI 35.6 (3.6) kg/m^2. No group differences existed at baseline. Linear mixed-effects models were used to compare group differences across all outcome changes. Compared to the HEC condition, the PNF intervention was associated with improved sleep quality (Pittsburgh Sleep Quality Index; B = -2.52; SE = 0.90; 95% CI-4.30 to -0.74; p=0.006). Stress, everyday cognition, and emotional eating behavior significantly changed over time (p<0.02), but there were no group differences. Analysis of feasibility outcomes are on-going. DISCUSSION/SIGNIFICANCE: Changing food intake timing 6 days per week, to exclude nighttime eating without mandating food quality/quantity change, may benefit many individuals living with obesity, stress and memory decline to improve their sleep. Improved sleep quality may lead to more health benefits over time.

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: 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: 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: 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.