OBJECTIVES/GOALS: To describe the impact of Trial-CARE (Coordination, Acceleration, and Recruitment Enhancement), a centralized service core at Washington University (WU), aimed at enhancing the capability of investigator-initiated multi-site clinical trials at WU and partner CTSA institutions. METHODS/STUDY POPULATION: Through review of our marketing materials and service tracking system we defined the following Trial-CARE offerings: Infrastructure: Trial-CARE is a centralized service core at WU. Whereby, a team member is sourced to an investigator-initiated multi-site clinical trial (II-MCT) to ensure the achievement of study milestones across any phase of the clinical trial life cycle. Team: Our team consists of research professionals with expertise in II-MCT project management, data management, and administrative/regulatory management. Services: * One free 60-minute case consultation * Tiers of Service * Academic Research Organization (ARO) support * Clinical Coordinating Center * Data Coordinating Center * II-MCT project management support * Time-limited targeted support RESULTS/ANTICIPATED RESULTS: Trial-CARE has completed 94 consultations in support of WU and partner CTSA institutions enabling the streamlining of study start-up; guidance for study recruitment, implementation, and operations; and offering resources to foster career development. Consultations can be completed at any phase in the clinical trial lifecycle, with Trial-CARE completing: * 12% in the idea phase * 45% in the grant development and submission stage * 28% after funding has been awarded Top reasons researchers connect with Trial-CARE about II-MCTs: * regulatory guidance (40%) * general information about Trial-CARE Services and II-MCTs (35%) * protocol development (21%) * data management (20%) * study budgeting (20%) DISCUSSION/SIGNIFICANCE: In response to a WU wide survey, Trial-CARE plans to generate informational webinars and is creating a clinical trial tracking dashboard, to pro-actively offer support services to researchers prior to grant funding. The goal is also to increase the percentage of consultations completed in the idea phase and the grant development and submission stage.

Digital badges can provide condensed competency-based knowledge enabling individuals a chance to explore specialized careers in clinical research. A digital badge can be an efficient pathway to introduce clinical research job roles and educate a larger diverse workforce for clinical research coordinator positions at AMCs. The New Jersey Alliance for Clinical and Translational Science (NJ ACTS) developed a digital badge with potential to broaden exposure to training opportunities for CRCs and improve their prospects for a career at Rutgers. This paper describes the development of a digital badge introducing individuals to the clinical research profession, especially for those who aspire to become a CRC. The badge was designed to include five domains (Scientific Concepts and Research Design, Ethical and Participant Safety Considerations, Clinical Study Operations and Site Management, and Data Management and Informatics). Participants assessed the badge for accuracy and presentation level. The results demonstrated that the competencies were met, and content was appropriate for someone with limited knowledge of clinical research. Survey results along with the Difficulty Index and Discrimination Index calculated for quiz questions supported the badge rank as foundational. Research is ongoing to evaluate the value of the badge to job acquisition, performance, and career growth.

OBJECTIVES/GOALS: Adoption of the Observational Medical Outcomes Partnership (OMOP) common data model promises to transform large-scale observational health research. However, there are diverse challenges for operationalizing OMOP in terms of interoperability and technical skills among coordinating centers throughout the US. METHODS/STUDY POPULATION: A team from the Critical Path Institute (C-Path) collaborated with the informatics team members at Johns Hopkins to provide technical support to participating sites as part of the Extract, Transform, and Load (ETL) process linking existing concepts to OMOP concepts. Health systems met regularly via teleconference to review challenges and progress in ETL process. Sites were responsible for performing the local ETL process with assistance and securely provisioning de-identified data as part of the CURE ID program. RESULTS/ANTICIPATED RESULTS: More than twenty health systems participated in the CURE ID effort.Laboratory measures, basic demographics, disease diagnoses and problem list were more easily mapped to OMOP concepts by CURE ID partner institutions. Outcomes, social determinants of health, medical devices, and specific treatments were less easily characterized as part of the project. Concepts within the medical record presented very different technical challenges in terms of representation. There is a lack of standardization in OMOP implementation even among centers using the same electronic medical health record. Readiness to adopt OMOP varied across the institutions who participated. Health systems achieved variable level of coverage using OMOP medical concepts as part of the initiative. DISCUSSION/SIGNIFICANCE: Adoption of OMOP involves local stakeholder knowledge and implementation. Variable complexity of health concepts contributed to variable coverage. Documentation and support require extensive time and effort. Open-source software can be technically challenging. Interoperability of secure data systems presents unique problems.

The hidden curriculum (HC), or implicit norms and values within a field or institution, affects faculty at all career stages. This study surveyed affiliates of a junior faculty training program (n = 12) to assess the importance of HC topics for junior faculty, mentors, and institutional leaders. For non-diverse junior faculty and their mentors, work-life balance, research logistics, and resilience were key HC topics. Coping with bias and assertive communication were emphasized for diverse junior faculty and mentors. Institutional norms and vision were essential for leaders, while networking was important for all groups. Future research should explore HC needs and potential interventions.

OBJECTIVES/GOALS: The Indiana CTSI is a partnership with Indiana University, Purdue University, University of Notre Dame, and Regenstrief Inst. IU’s Comprehensive Cancer Center is central to cancer research and education. A partnership between these critical entities ensures certain efficiencies. We provide a potential framework for community outreach efforts. METHODS/STUDY POPULATION: The Indiana CTSI’s partner institutions have long prioritized community outreach and engagement across the state. However, in environments with limited funding resources, efficiencies are critical to the sustainability of programs and efforts. All IN for Health, an initiative of the Indiana CTSI, has partnered with IU Simon Comprehensive Cancer Center in community outreach by evaluating current practices, aligning staffing, evaluating events, prioritizing outreach efforts, and strategic outcomes. A tool for evaluation was developed and the prioritization matrix along with a database of events now guide outreach efforts. The All IN for Health board continues to be highly engaged in providing feedback and developing strategies. RESULTS/ANTICIPATED RESULTS: This partnership has increased outreach to state-wide events, including urban and rural communities, as well as events contributing to the health of historically marginalized groups in the state. The challenge was our ability to be present at all community events that are critical to the success of all our partners, but most importantly the communities we serve. Opportunities to partner across non-academic and community health partners were evaluated with an assessment of All IN for Health efforts. The resulting approaches are used as an example or a potential framework from which to organize similar partnerships with the goal of advancing research and health equity. Through this partnership, we have extended outreach and added efficiencies, demonstrating creative implementation and strategies. DISCUSSION/SIGNIFICANCE: Unfortunately, limited funding prevents CTSAs and Cancer Centers from engaging everywhere they are needed. Translation research constantly encourages team science and collaboration. Our efforts are a reminder that the same approach applies to operations and synergizing the assets present within our community health and institutional partners.

The Advancing the Science of Mentorship: Future Directions for Sustainable Implementation and Evaluation of Mentorship Education for the Clinical and Translational Science Workforce conference was held in Madison, Wisconsin, in April 2023. The conference provided an engaging and scholarly forum for clinical and translational researchers from diverse backgrounds and career stages (including leaders at Clinical and Translational Science Award (CTSA) hubs and affiliated institutions) with a professional interest and commitment to improving and diversifying workforce development and fostering a climate of inclusive excellence through best practices in mentorship. Outcomes from the conference include an online resource and a new Community of Practice.

OBJECTIVES/GOALS: Serious video games are designed for skill-building and are increasingly being used for healthcare interventions with adolescents and young adults (AYAs). The study goal was to identify AYAs’ preferred game features, by demographic groups, to inform the development of a game to improve AYA’s engagement in their congenital heart disease (CHD) care. METHODS/STUDY POPULATION: Pediatric patients, 12-18 years old, completed surveys at a routine CHD care visit. Participants rated their likelihood of using games to learn CHD management skills (5-point Likert) and preferences for ten game features commonly used, such as: personalization (make your own avatar) and levels (unlock new, advanced stages as you do better). Participants selected one of three response options: 1=would make me less interested in the game, 2=doesn’t matter, 3=would make me more interested in the game. Descriptives and frequencies assessed interest in different game features. Chi-square tests were used to identify potential differences in game feature preferences by gender identity, age group (early/mid-adolescence vs. late adolescence), and race and ethnicity. RESULTS/ANTICIPATED RESULTS: Of 83 participants who completed surveys, the mean age was 15 years old (12-18; SD=1.73), 55% were male, 79% were Non-Hispanic White, and 70% were interested in video games for gaining CHD management skills. The top-rated game features were: levels (78%; unlock advanced stages), conflict (74%; face challenges), personalization (70%; create avatar), and story (70%; journey-based). The three lowest-ranked features were: time (29%; restricted time to complete challenge), competition (47%; score/play against others), strategy (53%; plan to reach goal). No significant differences in game feature preferences were found by demographic characteristics. DISCUSSION/SIGNIFICANCE: Most AYAs with CHD were interested in games, offering a promising avenue for future healthcare interventions. Given no significantly different preferences by demographics, the game may not require tailoring game features for certain groups. However, additional research with diverse participants is needed to fully inform game development.

OBJECTIVES/GOALS: We evaluated the long-term success of tissue engineered intervertebral discs (TE-IVDs) cultured in flexible (FPLA) or stiff (PLA) support materials, hypothesizing that FPLA would maintain disc height and tissue hydration in the minipig spine. METHODS/STUDY POPULATION: TE-IVD: NP cells were encapsulated in alginate and NP plugs were placed in the center of FPLA cages. AF cells were encapsulated in type I collagen and pipetted around NP plugs. Implantation: Empty FPLA cages (n=4), and TE-IVDs cultured in FPLA (n=4) were implanted at C3-4 or C5-6 following complete discectomy (DX) in skeletally mature minipigs (n=4). Imaging and Quantification: Terminal disc height indices (DHI) were calculated from weekly x-rays using a previously described method, and results were compared to the PLA pilot study. T2 MRI scans were taken of levels treated with TE-IVDs to quantify disc hydration as previously described. RESULTS/ANTICIPATED RESULTS: FPLA cages restored DHIs to native levels until endpoint. In contrast, PLA cages fractured, and terminal DHIs were statistically similar to DX levels. Of the four levels treated with TE-IVDs, 2 were displaced from the disc space. Stabilized levels yielded DHIs which were statistically similar to native IVD and greater than displaced and DX levels. Displaced levels yielded DHIs which were significantly lower than native and stabilized levels, but greater than DX levels (P<0.05). T2 MRIs of stabilized TEIVDs revealed that levels treated with a construct maintained tissue hydration which was significantly greater than levels treated with an empty cage or DX levels (P<0.0001), but which was about half the hydration of native disc tissue. DISCUSSION/SIGNIFICANCE: Implanting TE-IVDs with FPLA support cages leads to disc height maintenance and the stabilization of hydrated tissues in the spine, enhancing the long term success of TE-IVD implants and providing a basis for clinical translation.

Composite endpoints can encode multiple pieces of information and are increasingly adopted in clinical trials. Advocacy for using composite endpoints began decades ago in cardiovascular trials, leading to incorporation of patient-oriented outcomes and consideration of a hierarchical ranking system. The use of composite endpoints in coronavirus disease (COVID-19) trials has evolved similarly. We conducted a literature review to investigate the use of composite endpoints in acute heart failure and COVID-19 clinical trials. The results showed more frequent use of patient-oriented outcomes and ordinal composite endpoints in COVID-19 trials, which might be driven by global consensus on a set of common outcome measures.

OBJECTIVES/GOALS: Venous thromboembolism (VTE) is a major cause of morbidity and mortality. Due to its relatively low incidence, prospective studies are limited. This makes administrative claims a promising data source to study VTE. We sought to examine the reproducibility of results using different VTE definitions from the published literature. METHODS/STUDY POPULATION: We conducted a retrospective analysis of a random 10% sample of the 2010-2022 IQVIA LifeLink PharMetrics Plus™ database, an administrative claims database representative of the commercially insured population of the United States. We selected cancer patients undergoing major gastrointestinal surgery, who have a higher risk for postoperative VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]). VTE was defined using ICD-9-CM and ICD-10-CM codes using definitions from 4 individual published studies. We compared the 4 definitions with respect to the incidence of VTE and factors associated with post-discharge VTE using standard univariate and multivariable logistic regression models. The same logistic regression models were used for each of the 4 definitions. RESULTS/ANTICIPATED RESULTS: There were substantial differences in VTE coding among the 4 definitions (range 107 to 225 ICD-9/10 codes for DVT and 12 to 24 codes for PE). The eligible population comprised 2,360 patients (49% female) with a median age of 49 years (interquartile range 47-52 years). During the index surgery hospitalization, a total of 58, 62, 63, and 83 patients developed VTE using the 4 definitions. In the 2,126 patients eligible for VTE prophylaxis, a total of 108, 68, 73, and 107 patients developed post-discharge VTE (range for DVT 35 to 81, range for PE 39 to 76). On multivariable analysis, factors independently associated with VTE included age using 1 of 4 definitions, esophageal surgery type using 3 of 4 definitions, and liver surgery type and Elixhauser score using all 4 definitions. DISCUSSION/SIGNIFICANCE: The incidence of VTE is directly affected by differences in ICD-9/10 codes used. Definitions for important clinical outcomes should be standardized when using administrative claims data in order to improve reproducibility of findings.

OBJECTIVES/GOALS: Implementation science evaluations are often too time-intensive to provide actionable feedback during implementation, suggesting the need for more agile methods. We present an evaluation of the World Health Organization’s Emergency Care Toolkit implementation in Zambia using rapid qualitative methods to provide timely feedback. METHODS/STUDY POPULATION: We evaluated the implementation of the Emergency Care Toolkit in eight general and referral hospitals in Zambia in 2023 using a rapid-cycle, qualitative template analysis approach grounded in the Consolidated Framework for Implementation Research (CFIR). We gathered qualitative data from operational field notes, focus groups, and key informant interviews of administrators, clinicians, nurses, and support staff in all eight hospitals in Zambia. We parsimoniously applied CFIR constructs and tool-specific codes, focused on barriers and facilitators, to allow for rapid but comprehensive cross-case analysis. The results were used to generate a matrix of stakeholder-relevant, plain-language barriers and facilitators for each tool. RESULTS/ANTICIPATED RESULTS: We completed eight site visits with focus groups and interviews following initial implementation in September 2023 to gather firsthand knowledge related to implementation of the Toolkit. The CFIR-focused coding accelerated analysis by centering on barriers and facilitators for each tool while maintaining a comprehensive evaluation framework. Summary tables of barriers and facilitators were easily interpreted by lay stakeholders. Visualization in tables allowed for identification of common themes across tools and hospitals, making comprehensive recommendations to the implementation and dissemination process quickly possible. We anticipate the study findings will empower implementing partners to make timely, actionable improvements. DISCUSSION/SIGNIFICANCE: Rapid-cycle qualitative implementation evaluations allow for rigorous yet timely feedback on the implementation process compared to traditional methods. This efficient strategy is particularly important in resource-constrained environments where inefficient implementation wastes limited resources and create delays that cost lives.

Social determinants of health affect clinical and translational research processes and outcomes but remain underreported in empirical studies. This scoping review examined the rate and types of social determinants of health (SDoH) variables included in the JCTS translational research studies published between 2017 and 2023 and included 129 studies. Most papers (91.7%) reported at least one SDoH variable with age, race and ethnicity, and sex included most often. Future studies to inform the role of SDoH data in translational research and science are recommended, and a draft SDoH data checklist is provided.

OBJECTIVES/GOALS: We report an automated manufacturing system, and a series of cylindrical multi-layer microfluidic artificial lungs manufactured with the system and tested for fluidic fidelity and function. METHODS/STUDY POPULATION: A Roll-to-Roll (R2R) system to engrave multiple-layer devices was assembled. A 100 um-thick silicone sheet passes through an embedded CO2 laser engraver, which creates patterns of any geometry on the surface. The sheet is plasma-activated to create an irreversible bond, and rerolled into a processed device. Unlike typical applications of R2R, this process is synchronized to achieve consistent radial positioning. This allows the fluidics in the device to be accessed without being unwrapped. The result is a cylindrical core surrounded by many layers of microfluidic channels that can be accessed through the side of the device or through fluidic vias. This core is cut to expose the microfluidic layers, and then installed into a housing which routes the fluids into their respective microfluidic flow paths. RESULTS/ANTICIPATED RESULTS: To demonstrate the capabilities of the R2R manufacturing system, this method was used to manufacture multi-layer microfluidic artificial lungs (µALs). Gas and blood flow channels are engraved in alternating layers and routed orthogonally. The close proximity of gas and blood separated by gas-permeable PDMS permits CO2 and O2 exchange. Three µALs were successfully manufactured. Their flow paths were visualized using dyed water and checked for leaks. Then they were evaluated using water for pressure drop and CO2 gas-exchange. The top performing device had 15 alternating blood and gas layers. Test with whole blood demonstrated oxygenation from venous (70%) saturation levels to arterial (95%) saturation levels at a flow rate of 3 ml/min. DISCUSSION/SIGNIFICANCE: The ability to cost-effectively produce high surface area microfluidic devices would bring many small-scale technologies from the realm of research to clinical and commercial applications. In particular, most microfluidic artificial lungs only have small rated flows due to a lack of manufacturing processes able to create high surface area devices.

OBJECTIVES/GOALS: Developing pharmacokinetic (PK) models to guide selective serotonin reuptake inhibitor (SSRI) dosing in youth is costly, time-intensive, and requires large numbers of participants. We evaluated the use of remnant blood samples from SSRI-treated youth and developed precision PK dosing strategies. METHODS/STUDY POPULATION: Following IRB approval, we used a clinical surveillance platform to identify patients with routine phlebotomy within 24 hours of escitalopram or sertraline dosing. Remnant blood samples were obtained from youth aged 5–18 years, escitalopram and sertraline concentrations were determined, and clinical characteristics (e.g., age, sex, weight, concomitant medications that inhibit sertraline or escitalopram metabolism) and phenotypes for CYP2C19, the predominant enzyme that metabolizes these SSRIs, were extracted from the electronic medical record (EMR). A population PK analysis of escitalopram and sertraline was performed using NONMEM. The influence of clinical variables, CYP2C19, and dosing was evaluated from simulated concentration-time curves. RESULTS/ANTICIPATED RESULTS: Over 21 months, we collected315 samples from escitalopram-treated patients (N=288) and 265 samples from sertraline-treated patients (N=255). In youth, escitalopram and sertraline exposure (concentrations over time) and specific pharmacokinetic parameters (e.g., clearance) were influenced by CYP2C19 phenotype, concomitant CYP2C19 inhibitors, and patient-specific characteristics. Escitalopram and sertraline concentrations from remnant blood samples were 3.98-fold higher and 3.23-fold higher, respectively, in poor metabolizers compared to normal metabolizers (escitalopram, p<0.001) and compared to normal, rapid, and ultrarapid metabolizers combined (sertraline, p<0.001). DISCUSSION/SIGNIFICANCE: Combining remnant blood sampling with pharmacogenetic-integrated EMR data can facilitate large-scale population PK analyses of escitalopram and sertraline in youth. This real-world approach can be used to rapidly develop precision SSRI dosing strategies, including slower titration and reduced target doses in CYP2C19 poor metabolizers.

Despite having the same underlying genetic etiology, individuals with the same syndromic form of intellectual developmental disability (IDD) show a large degree of interindividual differences in cognition and IQ. Research indicates that up to 80% of the variation in IQ scores among individuals with syndromic IDDs is attributable to nongenetic effects, including social-environmental factors. In this narrative review, we summarize evidence of the influence that factors related to economic stability (focused on due to its prevalence in existing literature) have on IQ in individuals with syndromic IDDs. We also highlight the pathways through which economic stability is hypothesized to impact cognitive development and drive individual differences in IQ among individuals with syndromic IDDs. We also identify broader social-environmental factors (e.g., social determinants of health) that warrant consideration in future research, but that have not yet been explored in syndromic IDDs. We conclude by making recommendations to address the urgent need for further research into other salient factors associated with heterogeneity in IQ. These recommendations ultimately may shape individual- and community-level interventions and may inform systems-level public policy efforts to promote the cognitive development of and improve the lived experiences of individuals with syndromic IDDs.

OBJECTIVES/GOALS: Clinical and translational science needs to address roadblocks to translational processes. We conducted a survey at two institutions, a private medical school and a large public university, to understand the frequency and distribution of barriers and roadblocks to research. METHODS/STUDY POPULATION: We reviewed the literature to compile a pool of barriers and roadblocks and convened a panel of relevant stakeholders to develop a 20-item questionnaire. Survey respondents were asked to select and prioritize the five leading clinical and translational roadblocks, provide information regarding their academic degrees and rank/position, complete open-ended items regarding their areas of research, and optionally add additional remarks in a comment box. The survey was disseminated in August 2022 via REDCap to faculty and staff with active research protocols at Baylor College of Medicine and the University of Houston. RESULTS/ANTICIPATED RESULTS: In total, 227 respondents completed the survey. Their disciplines were basic science (29.5%), translational research (52.9%), clinical research (55.5%), community-engaged research (9.7%), and educational research (9.7%). Respondents identified 1) lack of access to trained research coordinators, 2) lack of understanding about different resources that facilitate research, 3) complex regulatory environment and delays, 4) fragmented infrastructure for administrative and fiscal processes, and 5) inadequate funding for pilot projects to foster new research. Other roadblocks included lack of established community stakeholder partnerships, inadequate access to medical record data, and limited biostatistical support. In the comments, several respondents noted that all items included were important. DISCUSSION/SIGNIFICANCE: Research workforce recruitment/training was the highest priority followed by lack of access to information and administrative bottlenecks. We are building an online portal to increase awareness and simplify access to competency-based training and research services. Initiatives are underway to address other roadblocks.

The Centers for Medicare & Medicaid Services have mandated that hospitals implement measures to screen social determinants of health (SDoH). We sought to report on available SDoH screening tools. PubMed, Scopus, Web of Science, as well as the grey literature were searched (1980 to November 2023). The included studies were US-based, written in English, and examined a screening tool to assess SDoH. Thirty studies were included in the analytic cohort. The number of questions in any given SDoH assessment tool varied considerably and ranged from 5 to 50 (mean: 16.6). A total of 19 SDoH domains were examined. Housing (n = 23, 92%) and safety/violence (n = 21, 84%) were the domains assessed most frequently. Food/nutrition (n = 17, 68%), income/financial (n = 16, 64%), transportation (n = 15, 60%), family/social support (n = 14, 56%), utilities (n = 13, 52%), and education/literacy (n = 13, 52%) were also commonly included domains in most screening tools. Eighteen studies proposed specific interventions to address SDoH. SDoH screening tools are critical to identify various social needs and vulnerabilities to help develop interventions to address patient needs. Moreover, there is marked heterogeneity of SDoH screening tools, as well as the significant variability in the SDoH domains assessed by currently available screening tools.