Community research advisory councils (C-RAC) bring together community members with interest in research to support design, evaluation, and dissemination of research in the communities they represent. There are few ways for early career researchers, such as TL1 trainees, to develop skills in community-engaged research, and there are limited opportunities for C-RAC members to influence early career researchers. In our novel training collaboration, TL1 trainees presented their research projects to C-RAC members who provided feedback. We present on initial evidence of student learning and summarize lessons learned that TL1 programs and C-RACs can incorporate into future collaborations.

This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVID-19 trials. The paper adopts a descriptive approach, eschewing analysis of data-driven efficacy of these efforts, and instead provides a comprehensive account of strategies utilized. The Accelerate COVID-19 Treatment Interventions and Vaccines (ACTIV) public–private partnership launched early in the COVID-19 pandemic to develop clinical trials to advance SARS-CoV-2 treatments. In this paper, ACTIV investigators share challenges in conducting research during an evolving pandemic and approaches selected to engage communities when traditional strategies were infeasible. Lessons from this experience include importance of community representatives’ involvement early in study design and implementation and integration of well-developed public outreach and communication strategies with trial launch. Centralization and coordination of outreach will allow for efficient use of resources and the sharing of best practices. Insights gleaned from the ACTIV program, as outlined in this paper, shed light on effective strategies for involving communities in treatment trials amidst rapidly evolving public health emergencies. This underscores critical importance of community engagement initiatives well in advance of the pandemic.

OBJECTIVES/GOALS: Our vision is to build community amongst the Midwest CTSAs, harnessing our collective expertise to collaborate on translational science challenges and meet the needs of our region. We aim to create opportunities to network, share ideas, brainstorm solutions, address translational science topics, and achieve a range of deliverables. METHODS/STUDY POPULATION: Three individuals from the Chicago CTSAs (NUCATs, CCTS, and ITM) had been networking for a year and desired to increase opportunities to collaborate amongst other CTSAs. We developed an initial vision for a new group that would extend across the region, and we invited the TIN POCs from 16 Midwest CTSAs to join. In September, 2022, the group was launched with 20 members from 12 CTSAs. We hosted 12 monthly meetings via Zoom to discuss various topics (i.e., staffing, career training, e-consent, research design, and recruitment tools) via round tables or presentations. We developed a Google Sites website with resources, a discussion forum, and a group calendar. We solicited feedback via survey and follow-up discussion (i.e., most valuable about the group and what can be improved). RESULTS/ANTICIPATED RESULTS: During the past year, our membership grew to more than 30 participants, representing 16 CTSAs in nine Midwest states (IL, IA, IN, MI, MN, MO, KT, OH, WI). We engaged a total of 45 individuals at our meetings, with an average of 11 participants per meeting. Our discussions were lively and stimulated additional conversations, requests for guidance, sharing resources, etc., beyond the meetings. Feedback from the group was overwhelmingly positive. Members found many aspects of the group to be valuable (i.e., learning initiatives, processes, and best practices at other CTSAs) and provided practical suggestions for improvement (i.e., themes across a quarter or year). Members expressed interest in additional collaborations such as subcommittees, papers, and other initiatives. DISCUSSION/SIGNIFICANCE: We created a regional CTSA community that is very enthusiastic to convene, share innovations developed at their CTSA hubs, and assist one other. Future directions include an in-person retreat in the spring. Our approach can serve as a potential roadmap for developing regional CTSA collaborative groups across the nation.

OBJECTIVES/GOALS: The objectives are 1) to describe the creation and implementation of a Clinical Research Feasibility Program at the University of Miami Miller School of Medicine (UMMSOM), and 2) to share early findings demonstrating its effectiveness in improving research operations which may be helpful for other academic medical centers. METHODS/STUDY POPULATION: Many clinical trials are closed prematurely because of low accrual or not being able to meet the target enrollment. The Miami CTSI and UMMSOM Executive Dean for Research office collaborated to establish the Research Feasibility Committee (RFC) focusing on clinical trial selection with upfront feasibility and recruitment planning. Program implementation included: 1) selecting faculty with successful clinical trial track records as committee members; 2) developing processes, tools, and governance; 3) feasibility pilot testing; and 4) feasibility program roll out and refinement. The feasibility review process starts with the PI/Designee completing a REDCap study intake form, followed by an administrative review to ensure completeness of the form. The RFC chair assigns reviewers for the studies. RESULTS/ANTICIPATED RESULTS: The RFC went live on September 1, 2022 reviewing industry sponsor clinical research studies. The RFC conducts a systematic feasibility assessment of the study protocol, operational requirements, enrollment barriers, institutional resources, and study budget (if available) for all applicable research studies prior to IRB submission and contract negotiation at the UMMSOM. To date, the RFC has received over 270 submissions. Based on feedback from users, the committee has made changes to improve the comprehension of questions and added questions to ensure capturing of critical information to assess study feasibility. Initial metrics suggest simply implementing the review process has decreased the number of clinical trial submissions: average number of studies per quarter was 41 pre-RFC vs 24 post RFC. DISCUSSION/SIGNIFICANCE: The development and implementation of the RFC involved many stakeholders from the research enterprise. Clear and frequent communication to the research community was a key factor in the program’s success. The next phase is assessing the impact of the RFC, such as preserving vital resources for trials more likely to be successful.

OBJECTIVES/SPECIFIC AIMS: (1) To evaluate the association of patient and clinical factors with adherence to adjuvant hormone therapy (HT). (2) To examine the association of HT-related symptoms and the extent of remediation with early discontinuation of hormone therapy. METHODS/STUDY POPULATION: Retrospective cohort study of risk factors for interruption and early discontinuation of adjuvant hormone therapy in hormone receptor-positive nonmetastatic breast cancer patients diagnosed between 2009 and 2015. This study will include incident hormone receptor-positive breast cancer patients who initiated their HT and were followed at Tufts MC until Dec 31, 2016. Primary data source is electronic medical records (EMRs) RESULTS/ANTICIPATED RESULTS: The primary outcome of this study is early discontinuation to HT, defined as the first treatment gap of greater than or equal to 180 days following the initiation of HT. Treatment interruption, defined as any patient- or provider-initiated treatment gap of ≥ 2 weeks, will be examined as the secondary endpoint. Any HT-related symptoms occurred during a follow-up interval will be captured and categorized into five major types (i.e., vasomotor, neuropsychological, gastrointestinal, gynecological, and musculoskeletal symptoms). Onset and duration of a HT-related symptom will be recorded. Severity of the symptoms will also be rated by clinical oncologists. Remediations in response to HT- related symptoms will be collected and categorized into to two groups (pharmacological or non-pharmacological) and whether they were patient- or provider-initiated. Response to a remediation is defined as complete relief, partial relied, no relief, or with worsening symptoms. Response to a treatment change (i.e., HT switch or hold) was collected separately but using the same criteria. Analyses will be performed on the association between patient and clinical factors with rates of nonadherence (unplanned treatment interruption and/or early discontinuation) of hormone therapy, respectively. We also will explore whether patients with elevated symptoms and/or incomplete remediation will have earlier discontinuation of hormone therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: Through formal chart review, we will establish a dataset that contains highly detailed information about treatment-emergent symptoms and remediations, which will enable us to quantitatively assess the impact of these treatment factors on adherence to hormone therapy for breast cancer. The in-depth analysis of risk factors associated with nonadherence to hormone therapy will inform development of interventions to improve cancer outcomes.

OBJECTIVES/SPECIFIC AIMS: Physical inactivity and mineral imbalances greatly contribute to morbidity and mortality in patients with end-stage renal disease (ESRD). Barriers for engaging in physical activity and adhering to the hemodialysis diet have been reported predominantly with white participants from countries other than Puerto Rico. Therefore, this study’s aims were to explore the barriers and facilitators that Hispanic adults with end-stage renal disease encountered for engaging in physical activity and adhering to the hemodialysis diet. METHODS/STUDY POPULATION: Three focus groups were conducted among 19 adults living with ESRD who received services from a renal center in Puerto Rico. Sessions were recorded, transcribed, and coded first using inductive methods. RESULTS/ANTICIPATED RESULTS: The presence of fatigue, lack of acceptance of the renal condition, and lack of knowledge of appropriate exercises for patients in hemodialysis were the most frequently reported barriers to engage in physical activities. Cost of the renal diet, limited availability of the renal diet products, the restrictive nature and the lack of Puerto Rican taste of the renal diet, and inadequate educational materials were the most frequent barriers to adhere to the hemodialysis diet reported by the sample. The most commonly reported facilitators to engaging in physical activities were having a positive attitude, opportunities for group exercises, and listening to Hispanic music while exercising. Health benefits, family support, having financial resources, availability of community resources, and having willpower were the most commonly reported facilitators to adhere to the hemodialysis diet. DISCUSSION/SIGNIFICANCE OF IMPACT: We identified a number of culturally relevant individual, interpersonal, institutional, and community-related barriers and facilitators to physical activity and adherence to the hemodialysis diet in patients with ESRD living in Puerto Rico. Evidence-based solutions to overcome these barriers and strategies for enhancing these facilitators should be addressed in future studies aimed at increasing the level of physical activity and increasing adherence to the hemodialysis diet in patients with ESRD living in Puerto Rico.

OBJECTIVES/SPECIFIC AIMS: The study aims to understand if pro inflammatory epicardial white adipose phenotype is positively associated with coronary atherosclerosis, while the brown adipose phenotype is negatively associated. Primary outcome is association between epicardial fat fraction and coronary atherosclerosis and cardiac function. Secondary outcome is transcriptomic and lipidomic profiling between epicardial, extra pericardial, and subcutaneous depots and how these profiles correlate with fat fraction. METHODS/STUDY POPULATION: Recruited patients undergoing open-heart surgery provided informed consent at their second visit and underwent laboratory testing and imaging (cardiac magnetic resonance including water-fat imaging and coronary calcium computed tomography) prior to their surgery. Cardiac function such as cardiac chamber volume, mass, function, and strain, and depo-specific fat fraction were calculated from cardiac MR and Agatston calcium score and epicardial adipose volume from CT images. At the time of surgery, a tissue specimens from the epicardial, extrapericardial, and subcutaneous depots were obtained for transcriptomic and lipidomic analysis. Linear and logistic regression analyses adjusted for other variables were performed to evaluate significance level between variables. RESULTS/ANTICIPATED RESULTS: 37 subjects were enrolled in the study, 13 (35%) of which were women. Cardiac function and fat fraction was quantified in all patients, whereas tissue analyses were performed in 22 patients. Epicardial and extrapericardial fat fraction were independently associated with coronary atherosclerosis (p-value 0.01 and 0.04 respectively) Only epicardial fat fraction was negatively associated with global circumferential shortening of the left ventricle (0.03), while neither the extrapericardial fat fraction nor epicardial adipose volume were not (p =0.33 and 0.97 respectively) All three adipose depots have unique gene signatures with differentially expressed genes and pathways. RNA sequencing of epicardial, extrapericardial, and subcutaneous depots demonstrated tight clustering of epicardial and subcutaneous signatures based on PCA analysis (Figure 2). 19 lipid classes and 59 lipids showed differential expression between at least 2 of the fat depots (Figure 3). Hierarchal clustering of the lipids showed that epicardial and extrapericardial depots were more closely related than subcutaneous adipose. Plasmenyl-phosphatidylcholines, with an ether-linked fatty acid at the sn-1 position of the lipid, were higher in subcutaneous fat while most other lipids were higher in epicardial fat per tissue weight, such as ceramides (p=0.002). DISCUSSION/SIGNIFICANCE OF IMPACT: Epicardial, extrapericardial, and subcutaneous adipose depots express different lipidome and transcriptome signatures and different pathways. GSEA analysis demonstrated enrichment of genes related to antigen presentation and B cell immunity in epicardial compared to subcutaneous adipose tissue. Epicardial fat fraction is associated with coronary atherosclerosis and decreased left ventricular global circumferential shortening as an early predictor of decreased left ventricular stroke volume. Epicardial fat fraction is also associated with cermides which may play role in the development of coronary atherosclerosis and decreased cardiac function.

OBJECTIVES/GOALS: An environmental scansoughtto understand research processes, areas for improvement, and opportunities for collaborative quality improvement (QI)across the Northwest Participant and Clinical Interactions Network (NW PCI). METHODS/STUDY POPULATION: NW PCI site champions were invited for semi-structured single and group Zoom-based interviews. Interviewers asked participants about local research processes, strengths and weaknesses, existing infrastructure to support QI, and interest in collaborative QI across the Network. Audio transcripts were coded using Dedoose and analyzed with deductive and inductive coding. RESULTS/ANTICIPATED RESULTS: Between February and April 2023, 10 interviews collected data from 7 research decision makers and 7 staff members across 7 sites. Most participants (n=13, 92%) agreed the diagram shown during the interview was representative of the local process. Organizations consistently identified strengths and weaknesses within the domains of study start-up, recruitment, budgets, and compliance. QI infrastructure was inconsistent (n=5, 36%) and all (n=14, 100%) saw potential for success in multisite QI initiatives to enhance efficiency. DISCUSSION/SIGNIFICANCE: NW PCI sites use similar processes, share common strengths and weaknesses, and universally reported interest in collaborating on QI. Study startup was reported as both a strength and weakness within the same organization, requiring unpacking of key elements before pursuing QI initiatives.

The emergence of the COVID-19 pandemic required an immediate global clinical research response. The ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines)-3 trials and the ACTIV-associated Outpatient Treatment with Anti-Coronavirus Immunoglobulin trial used Good Participatory Practices (GPP) to develop materials for study implementation from a global network perspective. GPP guidelines offer a framework for engaging stakeholders throughout the research process. This paper provides an overview of the materials developed and their applicability in various settings, reports results from a survey of study site personnel on the materials’ usefulness, summarizes important lessons learned, and serves as a reference for networks eager to apply GPP. Survey results showed that flipbooks and overview videos were highly ranked. Stakeholder input was valuable in developing easily understandable participant-facing materials with culturally appropriate images. Materials should be available to submit with the initial protocol submissions to ethics committees, and in formats that accommodate a wide range of institutional resources, policies, and infection-control practices. This article emphasizes the importance of GPP, including stakeholder consultation, in developing materials that support clinical research and address language, cultural, and sociopolitical barriers during a pandemic. The findings will be used to optimize efforts and resource allocation for new and ongoing studies.

In this paper, we introduce the Team Effectiveness Model for Science (TEMS) and describe a multiphase set of interventions for forming a new team or developing an existing team. TEMS uses a shared mutual learning mindset as the model’s central and guiding element. It shows how team mindset leads to behavior and to results and how this affects the characteristics of effective team functioning. TEMS addresses two related questions: What are the variables that contribute to effective teams? and How do the variables need to be designed to make their relevant contributions? Team models often answer the first question without fully answering the second. By addressing three gaps, TEMS contributes to enhancing science team effectiveness. Gap 1 is the absence of explicit core values, assumptions, and norms that serve as the foundation for developing and maintaining science team effectiveness. Gap 2 is the absence of a process for integrating the science and relationship aspects of a science team. Gap 3 is the absence of team processes and structures that are derived from the team’s values, assumptions, and norms. Using TEMS to design new or intervene with existing teams focuses on shifting mindset, developing behavioral skills, and designing processes and structures congruent with the new mindset.

OBJECTIVES/SPECIFIC AIMS: Type 2 diabetes (T2D) is costly and burdensome, but strong evidence exists that lifestyle change and weight loss can improve glycemic control and lower co-morbidities for patients with T2D. We used national data to examine whether the frequency of diet and/or physical activity counseling for patients with T2D in ambulatory settings has been responsive to accumulation of evidence supporting lifestyle change. METHODS/STUDY POPULATION: We used National Ambulatory Medical Care Survey (NAMCS) data over the period 2005-2015 from 31,475 patients with provider-reported T2D. We built multivariate logistic regression models, adjusting for patient, provider, and practice level characteristics (i.e. patient demographics, physician specialty, site of care, and region), to assess changes over time in the provision of diet or exercise counseling during ambulatory care visits, as reported through provider/staff chart review. We also examined whether changes in counseling over time varied by key patient and provider characteristics. We used non-overlapping confidence intervals (CI) to assess for statistical significance. RESULTS/ANTICIPATED RESULTS: Proportions of patients with T2D who received diet or exercise counseling were no different over time: 30% in 2005 [95% CI: 25%-35%] and 25% in 2015 [95% CI: 18%-31%]. Adjusted models show Hispanic patients had higher likelihood of receiving diet or exercise counseling, compared to whites (OR: 1.38 [CI: 1.03-1.85] for diet; OR: 1.37 [CI: 1.01-1.85] for exercise), and younger age was associated with higher likelihood of diet or exercise counselling, compared to those over 75 (age 30-49, OR: 1.47 [CI:1.18-1.82] for diet OR: 1.63 [CI: 1.30-2.03] for exercise). Among provider and practice-level characteristics, metro area and type of provider were associated with higher odds of receiving any diet and/or exercise counseling with visits in a metro area (OR: 1.23 [CI: 1.03-1.48]) and with an advanced practice provider (OR: 1.77 [CI: 0.97-3.22] having higher likelihood of receiving any diet or exercise counseling. DISCUSSION/SIGNIFICANCE OF IMPACT: Up to 30% of Americans with diabetes received any diet or exercise counseling in ambulatory visits, and this remained low over a decade. There were significant differences in counseling across patient, provider, and practice characteristics. Future studies are needed to better understand what interventions might improve counseling in ambulatory settings.

OBJECTIVES/GOALS: The CTSA consortium’s Informatics Enterprise Committee has developed a maturity assessment model for Clinical Trial Management Ecosystems (CTME). This poster will show the improvements achieved using this model at the University of Iowa as well as guidance on how to apply it at other CTSA hubs. METHODS/STUDY POPULATION: The CTME maturity model consists of 11 categories including, study management; regulatory; financial; and reporting. Each category has 3 subcategories: standardization; complexity; and monitoring, while each subcategory is comprised of 1 to 5 maturity statements: initial; developing; aspiring; capable; and efficient. The maturity assessment team at Iowa—comprised of key personnel from clinical research and compliance, accounting, and administration—have used the CTME maturity model to assess Iowa’s research performance across the 11 categories. The initial maturity ratings for each category revealed any gaps in research operations, which led to developing strategies to address the gaps. RESULTS/ANTICIPATED RESULTS: The assessment team initiated a CTME maturity planning project—holding regular meetings to review Iowa’s CTME research maturity and plan changes to improve our CTME maturity ratings. This analysis is done at the statement level to minimize the scope of actions needed and keep resource loads for improvements low. Proposed improvements are assigned to a team member who serves as an “accountability leader.” Such leaders develop action plans aimed at increasing maturity at least one level. The leaders are responsible for acquiring the resources to carry out the plan. Each action plan identifies qualifiers reviewed by the team to confirm that the maturity level has been met. DISCUSSION/SIGNIFICANCE: The CTME maturity model has been shown to be effective in identifying gaps in organizational operations at the University of Iowa, where it has led to incremental steps to improve clinical research operations. The utilization of the model at other CTSA hubs will be discussed at this session.

OBJECTIVES/GOALS: A new mandate for Clinical & Translational Science Award (CTSA) Programs is for pilot grant funding to support clinical and translational science (CTS) projects that study challenges in the translational research pipeline. This pivot requires new structures and supports to help investigators design and implement high-quality CTS projects. METHODS/STUDY POPULATION: The Michigan Institute for Clinical & Health Research (MICHR) at the University of Michigan (U-M) has launched two rounds of pilot funding since March 2023. Faculty and staff across U-M’s three campuses, community members, and those at collaborating institutions and hospitals were eligible to apply. New pre-award supports included a CTS project framework; a recorded webinar that educated about CTS and the funding opportunity; office hours to provide tailored project feedback; a letter of intent to screen for alignment with CTS; and reviewer training for academic and community reviewers. Funded projects operate like 'mini cooperative agreements”, with MICHR experts partnering with awardees to refine evaluation plans, prepare work products, advise on dissemination, and navigate emergent challenges. RESULTS/ANTICIPATED RESULTS: The first round of funding was launched in the absence of pre-award supports; ten applications we received from faculty proposing translational research rather than CTS. We quickly re-released the FOA, expanding eligibility to staff. We received nine applications, ultimately funding four staff and one faculty studying operational challenges in translation and helping them create robust evaluation plans. We piloted the pre-award supports in our second round, with 40 individuals viewing our webinar and 11 attending office hours. Those who watched the webinar before attending office hours better understood how to embed CTS questions within their programs of research. We recently received 19 letters of intent, addressing both operational and scientific challenges, with 16 eligible to submit applications. DISCUSSION/SIGNIFICANCE: Education and personalized feedback seem to elicit a higher yield of CTS projects. Staff are already adept at solving operational challenges, so the pre-award supports were most critical for faculty accustomed to writing traditional translational research proposals. Staff have most benefited from guidance in evaluation and dissemination.

OBJECTIVES/GOALS: Our primary objective is to determine the demographic and linguistic characteristics of student research assistants (SRAs) in a large student-run free clinic associated with a mid-western university. Our secondary objective was to determine if the SRAs perceived any impact of those characteristics on their duties and ability to conduct research. METHODS/STUDY POPULATION: We plan to conduct a 15-question electronic survey of Student Research Assistants at the student run free clinic. There are a variety of projects that require varying levels of commitment from researchers, which will be aggregated. This survey has been modified from a previously validated survey that focused on the demographic and linguistic characteristics of pediatric research coordinators. This survey will be emailed out to student research assistants and will be done over a period of 3 months. The study population will be predominantly undergraduate students who are all interested in a career in healthcare, ages expected to range from 18-25. RESULTS/ANTICIPATED RESULTS: We anticipate that the majority of student research assistants will be older students and will be students who identify as non-white/caucasian, as the majority of students volunteering at this free clinic do not identify as white. Additionally, we anticipate that students will feel that their racial/ethnic identity will positively impact their recruitment efforts. We also anticipate that the ability of a student research assistant to speak another language is expected to positively affect their perceived recruitment efforts. We also anticipate that gender will influence the student researchers’ perceptions of their recruitment efforts. DISCUSSION/SIGNIFICANCE: An individual’s background can directly impact how they perceive their contributions towards research. Considering the paucity in research for underinsured and uninsured and the rise in undergraduate student research assistants, optimizing research efforts and SRA confidence is essential to increase the accuracy and efficiency of research.

OBJECTIVES/SPECIFIC AIMS: To further explore the role of vWF in the pathogenesis of scleroderma by identifying its location within the tissue of sample biopsies obtained as part of routine diagnosis with the use of immuno-histochemical staining. METHODS/STUDY POPULATION: We examined 8 skin biopsies from 2 patients with systemic sclerosis (SSc), 2 with localized scleroderma (LS) and 4 with JDM. Double immunofluorescence staining was performed in each tissue with antibodies against vWF and collagens type I and III. DAPI (4′, 6-diamidino-2-phenylindole) was also used for counterstaining of inflammatory cells. Tissue staining patterns were compared between groups. RESULTS/ANTICIPATED RESULTS: Biopsies were obtained from the upper extremity of 7 females and the lower extremity of 1 male. Median age, symptom duration, and serum levels of vWF antigen around the time of biopsy was 8 years (IQR 4.5-11), 5.5 months (IQR 2.5-7), and 245% (IQR 203-302 for 7 patients), respectively. All but 1 biopsy was performed prior to initiation of immunosuppressive therapy. Immunofluorescence staining showed a superficial and deep perivascular inflammatory cell infiltrate that co-localized with vWF in all tissues. There was expression of vWF in the extravascular tissue of patients with JScl co-localizing with collagen III in the reticular dermis (Figures 1 and 2). In comparison, vWF expression was restricted to the endothelium and did not co-localize with collagen in the dermis of patients with JDM (Figure 3). Patients with SSc had higher expression of vWF as compared to patients with LS. DISCUSSION/SIGNIFICANCE OF IMPACT: vWF may participate in the pathogenesis of cutaneous inflammatory conditions. We have demonstrated that vWF co-localizes with cellular inflammatory infiltrates in the perivascular areas and in the dermis of patients with JScl and JDM. We additionally speculate that vWF may participate in the pathogenesis of fibrosing skin diseases based on evidence of increased extravascular expression in the tissue of patients with JScl (vs. JDM), and its co-localization with collagen. vWF expression intensity in the dermis of JScl patients may relate to disease extension (SSc vs. LS).