Clinical trials are essential in the translation of biomedical discoveries to new clinical interventions and therapeutics. Successful multisite clinical trials require qualified site investigators with an understanding of the full spectrum of processes and requirements from trial identification through closeout. New site investigators may be deterred by competing demands on their time, the complexity of administrative and regulatory processes for trial initiation and conduct, and limited access to experienced mentor networks. We established a Clinical Trialist Training Program (CTTP) and complimentary Clinical Trials Bootcamp at our institution to address these barriers and increase the number of local site investigators enabled to lead successful clinical trials. An initial cohort of four CTTP scholars received salary support with protected time, didactic training, assistance with study identification and start-up navigation, and quarterly progress meetings. By the end of the 12-month program, this initial cohort identified 33 new trials, utilized feasibility assessments, and reported being on target to sustain their protected time from new clinical trials. Bootcamp attendees demonstrated increased knowledge of resources, offices, and processes associated with clinical trial conduct. Our results support providing compensated protected time, training, and access to experienced clinical research professionals to enable clinicians to become successful site investigators.

Objectives/Goals: Our goal for this project is to develop a metric that integrates the intersectional social and structural determinants of health and well-being into the existing policy development framework to impact the integration of such considerations on population mental health. Methods/Study Population: This project was developed from a case study module offered by the Translational Research Program at the University of Toronto. This course was designed to sharpen contextual inquiry skills and further develop a case through employing strategies, including outreach engagement with stakeholders, conducting informational interviews and formulating potential pathways forward based on the integration of insights from interdisciplinary perspectives. Results/Anticipated Results: The anticipated outcome would be improved mental health outcomes as measured by the Mental Health Commission of Canada’s Mental Health Indicators (Mental Health Commission of Canada, 2015) Discussion/Significance of Impact: Although there are established mental health indicators and policy development framework the two operate independently of each other. Our proposal bridge the gap between the sectors so that one may inform the other, and they can collectively formulate reflective and representative policies.

OBJECTIVES/GOALS: Platelets interact with leukocytes in the circulation to modulate inflammation in chronic diseases. In previous clinical study, we showed that platelet leukocyte interaction is reduced in the circulation of patients with CKD. Preclinical studies are needed to show whether these findings are a precursor to or a result of CKD. METHODS/STUDY POPULATION: We used mouse models (wild type and platelet-defect) and induced CKD with intraperitoneal cisplatin injections. We measured platelet leukocyte interactions before and after CKD induction in the two models. RESULTS/ANTICIPATED RESULTS: We found platelet-leukocyte interaction to reduce after CKD induction in both wild type and platelet-defect mice. This coincided with a pro-inflammatory state in these mice, as measured by serum TNFalpha levels. Specifically, pro-inflammatory state was exacerbated in CKD of mice with platelet-defects compared to the wild type. DISCUSSION/SIGNIFICANCE: These findings recapitulate translational findings in human CKD samples and confirm that CKD state results in reduced platelet-leukocyte interactions in the circulation, and this change imparts a pro-inflammatory state in the CKD state.

OBJECTIVES/GOALS: Healthcare organizations and payers are moving from accountability to effectiveness frameworks. Static vendor contracts for full-scale implementation limit organizations' ability to evaluate impact before scale-up, or to iteratively improve. Our team science innovation employs science and learning methods as systems engage vendors. METHODS/STUDY POPULATION: Our team science innovation is a method to assess and model impact of interventions at scale in healthcare delivery systems. We are integrating expertise in learning processes of an academic medical center (UCLA CTSI) with the organizational knowledge and methodological expertise of the nation’s largest Medicaid managed care plan (LA Care Health Plan), which has over 2 million members. The LA Care Advanced Analytics Lab has unique capability in machine learning, while enables deep learning of variation. Our innovative product is a template to quickly mobilize evaluation and learning for a diverse population in a varied and distributed delivery system. The template design enables rapid learning for the full-scale policy implementation often imposed by government, and in the short timeframes involved. RESULTS/ANTICIPATED RESULTS: LA Care and the UCLA CTSI partnered to provide subject matter expertise and design effective pilots for interventions such as transitional care services, complex care management, and physician home visit strategies, accounting for confounding factors affecting the intervention and outcome. So far, collaborative modeling and design has produced a successful pilot of a physician home visit program intended to reduce avoidable emergency department visits. This pilot quickly revealed several major changes that would need to be incorporated for the contracted vendor to produce results if operated at scale, further informed by machine learning, in sufficient time to inform the contracting process. There are multiple evolving applications, including housing/homelessness. DISCUSSION/SIGNIFICANCE: Integrating the large data and analytics of a large healthcare organization with learning methods from the CTSI -- including learning from variation and designs for studying impact during scale-up -- fosters academic-community team science that could significantly improve the value of our largest delivery systems, public and commercial.

Objectives/goals: This project will focus on identifying the barriers that result in low adherence to quality care indicators that establish effective and efficient pediatric emergency care. The overall objective is to understand motivations behind adherence (or lack thereof) and find solutions to facilitate compliance. Methods/Study Population: This study will use a mixed-methods design to investigate the barriers. Quantitative data will be collected through a survey provided to healthcare providers involved in pediatric emergency care, including physicians, nurses, and administrative staff in both pediatric and general hospitals. Qualitative data will be collected through semi-structured interviews with a group of respondents to gain insight on their experience regarding compliance. Quantitative data will be analyzed using statistical analyses while qualitative data will undergo a thorough thematic analysis. Both sets of data will be reviewed to identify themes and differences in barriers across hospital types and healthcare roles. Results/Anticipated Results: We will have gathered insights and perspectives from key stakeholders that are relevant to our study to ensure a comprehensive understanding of any potential implications that may arise from our study. We anticipate that the specific results will highlight key differences in adherence between pediatric and general hospitals. The study is expected to identify specific barriers hindering compliance with established guidelines in both settings. The results may be used to increase adherence to critical quality indicators and improve patient care. Discussion/Significance of Impact: Pediatric injury care prioritizes the immediacy of care for children with acute illness and injury. With certain hospital protocols not being adhered to, there is a risk of wasting crucial time and resources that can affect patient care outcomes. The results would provide recommendations to improve and increase efficiency in pediatric injury care.

OBJECTIVES/GOALS: To introduce the new Team Science Community Toolkit, co-created by community and academic partners, and showcase its potential to empower Community Organizations (COs) in achieving equity in community-engaged research (CER). METHODS/STUDY POPULATION: In response to the challenges faced by COs in CER collaborations, qualitative interviews were conducted with CO staff from historically marginalized communities. These interviews informed the development of the Team Science Community Toolkit, a collaborative effort involving a Community Advisory Board (CAB) and Team Science experts from Northwestern University. The toolkit, designed using a community-based participatory research approach, incorporates the Science of Team Science and User-Centered Design principles. Integrated into the NIH-sponsored COALESCE website, it includes templates, checklists, and interactive tools, along with a real-world simulation, to support COs in all stages of the research process. RESULTS/ANTICIPATED RESULTS: Focus groups and usability testing involving external community experts validated the toolkit’s content and usability. Participants expressed enthusiasm and a sense of empowerment, indicating that the toolkit allows them to actively shape research processes and infuse their specific voices and needs into their partnerships. The toolkit is designed to support breaking down barriers like jargon and cultural adaptability to improve accessibility and open conversation. The impact of this Team Science focused toolkit is under evaluation. This presentation will showcase the toolkit, detail its collaborative development, and explore potential applications, ultimately offering a path to more equitable and valuable community-based research. DISCUSSION/SIGNIFICANCE: By providing COs with the resources and knowledge to participate as equal partners in research collaborations, it enhances self-advocacy, transparency, and equity. The toolkit has the potential to utilize Team Science to foster productive communication in community-academic research partnerships.

Objectives/Goals: To identify gaps in policy that influence enrollment trends of patients with multimorbidity in Phase III clinical trials. We aim to propose policy recommendations for increasing use of real-world evidence (RWE) that increases safety and efficacy information for patients with multimorbidities. Methods/Study Population: Conduct a systematic policy analysis on the current regulatory landscape of RWE, referencing the 2020 FDA Guidance “Enhancing the Diversity of Clinical Trial Populations.” Evaluate guidelines using the Department of Health and Human Services’ (HHS) 2016 Regulatory Impact Assessment (RIA) Framework. Utilize the Center for Drug Evaluation and Research’s New Molecular Entity Database to identify novel hypertensive drugs approved after 2006, and assess clinical studies’ alignment with the 2020 Guidance. Review additional policies, FDA guidelines, and ICH documents to establish baseline compliance. Two case studies will evaluate past policy impacts on drug development. Assess costs and benefits of increasing multimorbid patient enrollment to inform a policy framework. Results/Anticipated Results: Anticipated results include all components of the HHS’s RIA and a policy framework informed by the assessment. To identify problems, an analysis of clinical trial exclusion criteria in novel hypertensive drugs will be conducted to show diversity and enrollment gaps in regulatory policy, referencing the FDA’s 2020 Guidance. The RIA’s cost–benefit analysis will highlight costs faced for utilizing RWE and expanding enrollment criteria in Phase III studies. The cost–benefit analysis, RIA, and case studies will inform a policy framework that explains dynamics between stakeholders and outline policies that increase clinical trial representation in ways that are less burdensome to sponsors and patients. Discussion/Significance of Impact: By understanding the barriers to enrolling participants with multimorbid conditions, we can outline incentives to increase diverse trial populations, helping healthcare providers choose more treatments for complex conditions. This research supports policy recommendations to make drugs more representative of conditions the population faces.

Dissemination and implementation (D&I) science is dedicated to studying how to effectively translate and apply research in real-world contexts. There has been increasing interest in health equity within the D&I field to ensure the equitable implementation of evidence-based programs/practices across a range of diverse populations and settings. At the same time, health equity researchers recognize the potential of D&I science to promote the more widespread dissemination, implementation, and sustainment of evidence-based interventions to address health inequities. The National Center for Accelerating Clinical and Translational Science Clinical and Translational Science Award (CTSA) Program has been a champion for community engagement and translational scholarship in its mission to improve individual and population health. The overall CTSA infrastructure and resources within and among CTSA hubs are well-equipped to facilitate a health equity focus to D&I across the phases of translational research. This paper proposes a framework that demonstrates the interaction and opportunities between health equity and D&I science and highlights how CTSAs can support and facilitate wider efforts in translational research with a focus on equitable D&I.

Demand for building competencies in implementation research (IR) outstrips supply of training programs, calling for a paradigm shift. We used a bootstrap approach to leverage external resources and create IR capacity through a novel 2-day training for faculty scientists across the four Texas Clinical & Translational Science Awards (CTSAs). The Workshop combined internal and external expertise, targeted nationally established IR competencies, incorporated new National Institutes of Health/National Cancer Institute OpenAccess online resources, employed well-known adult education principles, and measured impact. CTSA leader buy-in was reflected in financial support. Evaluation showed increased self-reported IR competency; statewide initiatives expanded. The project demonstrated that, even with limited onsite expertise, it was possible to bootstrap resources and build IR capacity de novo in the CTSA community.

OBJECTIVES/GOALS: We are using ethnographic methods and Dissemination and Implementation (D&I) frameworks to study barriers and facilitators to implementing ‘TeamMAPPS: Team Methods to Advance Processes and Performance in Science.’ TeamMAPPS is an evidence-based Team Science curriculum deployed as five online modules and being implemented across CTSA hubs. METHODS/STUDY POPULATION: For this pre-implementation study, we used the Implementation Mapping framework to understand likely barriers and facilitators, with the aim of designing implementation strategies and long-term outcome measures. Data included field notes from a two-day train-the-trainer, one visit to a key implementing site, and 27 interviews. Participants were four TeamMAPPS conceptualizers, four module designers, and 15 implementers from seven implementing sites, each with a CTSA hub (four were interviewed twice). We coded transcripts using the Consolidated Framework for Implementation Research (CFIR) to identify contextual barriers and facilitators to D&I, the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) D&I outcomes framework, and target competencies of TeamMAPPS. RESULTS/ANTICIPATED RESULTS: Priority D&I outcomes that emerged were adoption, reach, and effectiveness. Potential barriers/facilitators to “adoption” included institutional willingness to incentivize scientists to utilize TeamMAPPS, support for Team Science at CTSAs, and systems of rewards for scientists to undergo trainings. Anticipated barriers/facilitators for “reach” were closely tied to adoption, such as institutions’ ability to persuade or require scientists to take trainings. Other issues relevant to reach included the time it takes to time to complete TeamMAPPS and potentially fraught intra-team dynamics arising if modules are implemented as a whole-team intervention. Anticipated barriers/facilitators for “effectiveness” included having adequate tools to assess actual impact. DISCUSSION/SIGNIFICANCE: TeamMAPPS has the potential to accelerate advances in translational sciences across the CTSA consortium. As this D&I study proceeds we will continue Implementation Mapping and use the Expert Recommendations for Implementing Change (ERIC) to develop bundles of implementer-informed strategies to the effectively deliver TeamMAPPS among CTSAs.

Objectives/Goals: To present findings from a focus group study that evaluate clinical research professionals’ (CRPs) team science learning preferences. The study aims to better understand CRPs’ experiential perceptions of team science skills, training gaps, team cohesion, conflict, and contributions for their preferred team science training. Methods/Study Population: This study targeted CRPs across various roles in Academic Health Centers via focus groups. The focus groups will assess current skills, identify training gaps, and share experiences on team cohesion, team conflict, team contribution, and their thoughts and perceptions about clinical research professional team science training. The focus groups will be held via Zoom in the Autumn of 2024 with volunteer participants from an initial survey that was conducted earlier in 2024. We will report on combined data from multiple 90-minute focus groups, with approximately 6 participants per session. Results/Anticipated Results: The focus group facilitator’s guide includes questions informed by the CRP team science learning needs assessment results and other questions on team issues that would benefit from focused training. Focus group methods and demographic characteristics of the participants by role and experience level will also be presented. Qualitative analyses of recorded focus-group discussions will present key themes by demographic groups, and as a whole, these data will contribute to the development of CRP team science educational programs and toolkits. Discussion/Significance of Impact: CRPs are vital members of clinical translational science teams. Overlooking CRP team science training can negatively affect the efficiency and effectiveness of the clinical translational science enterprise. CRP team science skills will foster a more collaborative and productive research environment.

Objectives/Goals: This research aims to harness electronic health records (EHR) combined with machine learning (ML) to predict necrotizing enterocolitis (NEC) in preterm infants using data up to their first 14 days of life. We aim to provide interpretable results for clinical decisions that can reduce infant mortality rates and complications from NEC. Methods/Study Population: Through a retrospective cohort study using data from the University of Florida Integrated Data Repository and One Florida, we will develop machine learning models suitable for sequential data to predict NEC. Our inclusion criteria include very low birth weight (VLBW; < 1500g) infants born < 32 weeks gestation and EHR data availability from the first 14 days of life. We will include infants with NEC and infants without NEC to train our ML model. Exclusion criteria include infants diagnosed with spontaneous intestinal perforation and severe congenital anomalies/defects requiring surgery. Results/Anticipated Results: We anticipate that our model will provide an accurate and dynamic prediction for the risk of NEC in neonates using data up to the first 14 days of life. Our model will be interpretable to identify key risk factors and can integrate real-world clinical insights to increase early detection and improve patient outcomes. Discussion/Significance of Impact: The development of a model to predict NEC could be used in neonatal intensive care guidelines and protocols and could ultimately decrease mortality, reduce complications, improve the overall quality of care, and lower healthcare costs associated with NEC.

OBJECTIVES/GOALS: to investigate the potential impact of grandparental factors and multigenerational epigenetic inheritance on the development of ASD METHODS/STUDY POPULATION: Our study recruited participants from the CHARGE (Child Autism Risks from Genetics and the Environment) study, including grandparents, parents, and children. A questionnaire was used to gather information about the participants’ exposure to environmental factors. Saliva samples werecollected from 349 participants. Newborn dried blood spotsfrom probands and parents are still being collected from the California New born Registry. DNA was extracted from 349 saliva samples from 85 families and subjected to whole genome bisulfite sequencing (WGBS) to analyze DNA methylation. Sequence alignments and bioinformatic analyses will be performed using R packages called DMRichR and Comethyl. RESULTS/ANTICIPATED RESULTS: Sequence alignments and bioinformatic analyses are ongoing, utilizing DMRichR to identify individual genomic loci associated with ASD in each of the three generations and Comethyl to compare correlation patterns between methylation marks and selected variables, including grand parental exposures. New born blood spot collections of parents and probands are ongoing and will be used to identify potential ASD epigenomic signatures that are tissue and life-stage independent. DISCUSSION/SIGNIFICANCE: This research will provide new insights into the increased prevalence and underlying etiology of ASD that should pave the way for future research in the field. DNA Methylation signatures can help create molecular biomarkers which can be used together with behavioral clinical tests for diagnosis of ASD.

Educational tools for application of team science competencies in clinical research are needed. Our interdisciplinary group developed and evaluated acceptability of a virtual world game-based learning tool simulating a multisite clinical trial; performance hinges on effective intrateam communication. Initial implementation with clinical research trainees (n=40) indicates high satisfaction and perceived relevance to team science and research career goals. Game-based learning may play an important role in team science training.