Clinical research coordinators are increasingly tasked with a multitude of complex study activities critical to scientific rigor and participant safety, though more than half report not receiving appropriate training. To determine the reproducibility of an established clinical research workforce orientation program, collaborative partners across Clinical and Translational Science Award institutions seeded core principles and structure from Mayo Clinic’s Clinical Research Orientation program within Penn State University and the University of Mississippi Medical Center from 2019 to 2021. Training concepts were established and tied to those domains deemed critical by the Joint Task Force for Clinical Trial Competency for the conduct of clinical research at the highest levels of safety and quality possible. Significant knowledge and confidence gains and high overall program satisfaction were reported across participants and partner sites, despite programs being required to pivot from traditional, in-person formats to entirely virtual platforms as a result of the COVID-19 pandemic. The successful standardization and translation of foundational clinical research training has important efficiency and efficacy implications for research enterprises across the USA.

Diversification of the Translational Science workforce is a strategic goal for the National Center for the Advancement of Translational Science (NCATS) program. NCATS has identified the development of translational science education, training, and support for a diverse translational science workforce as key to advancing the growing field of translational science. An annual mixed-methods assessment has been conducted on Common Metrics data submitted by over 60 Clinical & Translational Science Awards (CTSA) programs nationwide and includes metrics addressing recruitment and retention of scientists with particular attention to underrepresented persons and women. This article describes a methodology for the development of From Insights to Action, a resource for guiding program implementation and strategic planning to develop a diverse clinical and translational science workforce. This was informed by the Common Metrics Initiative process and constituted of findings from qualitative interviews of a subset of CTSAs that participated. The dissemination of this guide had several impacts, including providing structural foci for the CTSA Fall 2020 program meeting centered on Diversity, Equity, and Inclusion in translational science; addressing NCATS’ goal of workforce diversity; and understanding the number of diverse graduates still engaged in research.

Patient recruitment, diversity, and retention continue to impede successful and representative clinical studies. This systematic review aims to assess the impact of decentralized methods on recruitment, retention, and diversity in recent clinical studies. A systematic search of literature reporting on recruitment in decentralized clinical studies was performed. Studies were reviewed for those reporting the primary outcome of recruitment in decentralized clinical trials, observational studies, or those covering the topic of clinical trials. Secondary outcomes included retention, participant diversity, and participant satisfaction. This systematic search returned 13 studies highlighting the role of decentralized methods impacting participant recruitment, retention, and diversity in clinical studies. Eleven reported improved recruitment using decentralized methods. Seven of these reported improvements directly compared to traditional methods. Seven studies reported positive retention outcomes, with four directly comparing decentralized methods with traditional methods. Six studies were reported to have trended toward increased diversity in the demographics of the sample population, including race or geographic location. Related reviews have stated a lack of published comparable data to determine if decentralized clinical methods improved recruitment and retention. Results suggest this review addresses such a gap, providing data on how decentralized methods such as virtual visits can positively impact recruitment and retention.

OBJECTIVES/GOALS: Regardless of their career choices, today’s biomedical researchers need to blend great science with core skills ininnovation and entrepreneurship (I&E). The objective of this NIH-funded education program was to develop and test a pragmatic training program to teach relevant I&E skills. METHODS/STUDY POPULATION: We used a modified Delphi approach to identify 15 relevant competencies for I&E and the essential topics to include in the program. Learner interviews identified preferences for online training programs (short, high-quality audio-visual content, ability to self-navigate, peer and instructor interactions). The inaugural program included 7 short, online courses that addressed how to identify and validate opportunities for innovation, sell your innovation to diverse audiences, assess its ethical consequences, work in teams, and develop resilience as an innovator. It also included mentor support, a team-based capstone project, and an optional in-person boot camp. RESULTS/ANTICIPATED RESULTS: 51 students enrolled and 41 participants from 9 institutions completed the program, including pre- and post-doctoral students and junior faculty. They organized into 10 teams to complete the capstone project, with 6 teams pitching their innovation to fellow students and mentors at the boot camp. Students rated satisfaction with courses highly overall, with 79% stating they would be disappointed if the program was no longer available. Preliminary results suggest participants increased their knowledge about and ability to perform tasks taught throughout the program. Suggestions for improvement included providing more practical advice and real-world examples to complement educational videos. DISCUSSION/SIGNIFICANCE OF IMPACT: The inaugural E4B program was well received and effective in increasing I&E skills. Improvements will include increased opportunity for mentor interactions and for advanced entrepreneurial training. The program is open for biomedical research trainees from all institutions with a CTSA award.

OBJECTIVES/SPECIFIC AIMS: The prevention, management, and treatment of HIV, STDs, and HCV requires continuous training that reflects contemporary best-practice and innovative care models. In order to improve the NYS AIDS Institute’s comprehensive web-enabled training program, which enhances the capacity of a diverse healthcare workforce, a needs assessment (NA) of our community of practice (CoP) is needed to better understand their training needs, circumstances, and instructional modalities preferences. The goal of the assessment was to better understand our CoP’s preferences of online trainings, and as a result to develop a “responsive design” system that will enhance user’s learning experience thus improving patient care. METHODS/STUDY POPULATION: We developed and deployed an NA survey using REDCap. The instrument consisted in 27 questions related to providers’ preferences on receiving continuing educational training and their use of technologies, including mobile platforms, online modules, webinars, and telehealth. As part of the recruitment strategy, several resources were deployed over a 1-month recruitment period including sequential email blasts, website promotion, and assessment links included in newsletters and social media. Weekly reminders were also used to promote the participation from our CoP. RESULTS/ANTICIPATED RESULTS: A total of 310 respondents participated in the NA, with 85.8% from NYS. 177 were clinicians (20.5% MD, 2.9% PA, 17.3% NP, and 16.3% RN) and 133 nonclinical providers (case/care managers, social workers, public health professionals, coordinators/administrators, and other). The participants worked in hospitals, community health centers, substance use centers, private practices, and state/local health departments. More than 90% of respondents indicated that they preferred both live/in-person and online training, and participants most strongly indicated that they stayed up-to-date on current developments through CDC, the AIDS Institute, and conferences. More than 60% of respondents considered that receiving CE credit for the training was very important and 28% indicated they would use training materials in Spanish if offered. In terms of technology, over 80% of the respondents preferred computers, but more 50% also used mobile devices (computer at home 61.8%, computer at work 85%, tablet 29.9%, iPhone 20.9%, Android 16.6%, other device 2.3%). DISCUSSION/SIGNIFICANCE OF IMPACT: Accessing an online CoP provided a useful opportunity to assess training needs and preferences of clinical and nonclinical providers. Most providers indicated that they were primarily likely to use a work computer to complete online training or secondarily a home computer. With a significant portion of respondents indicating use of tablets, smartphones, and other devices, online training opportunities should be developed with responsive design to assure flexibility and access. In addition to online training, participants indicated that they also strongly valued live, in-person training. Offering training with CDC and the NYS AIDS Institute branding, in Spanish, together with offering continuing education credit, were all seen as desirable training elements. Accessing this online CoP helped streamline and target training priorities and logistics.

Little has been published on the demographic composition of the clinical and translational science research workforce within the Clinical and Translational Science Awards (CTSA) Program despite the well-documented need for greater diversity in the biomedical research workforce. Analyses of workforce demographic reveal that women and members of underrepresented groups remain persistently underrepresented in the CTSA hub and training components principal investigators. In contrast, in the CTSA Program career development and training programs, females have greater representation as participants, and non-Whites were better represented in training programs.

ABSTRACT IMPACT: This study highlights the importance of creatine in developmental myelination and remyelination to investigate whether creatine provides a therapeutic value during a central nervous system (CNS) demyelinating insult with a potential value in patients with Multiple Sclerosis. OBJECTIVES/GOALS: Creatine is vital for ATP buffering in the brain. Interestingly, the cells that generate myelin express the main enzyme for creatine synthesis, Gamt. Patients with Gamt mutations display intellectual delays and impaired myelination. Therefore, we hypothesize that creatine is essential for developmental myelination and improves remyelination. METHODS/STUDY POPULATION: To investigate these hypotheses, we developed a new transgenic mouse model with LoxP sites flanking exons 2-6 of the guanidinoacetate methyltransferase (Gamt) gene where excision leads to expression of a green fluorescent tag allowing us to track the cells normally expressing Gamt. We used immunohistochemistry techniques to look at the corpus callosum, the main white matter tract in the brain, and evaluate the number of oligodendrocytes (OL), glial cells responsible for generating myelin. We also used the cuprizone model of toxic demyelination to investigate whether dietary creatine and cyclocreatine, a planar analog of creatine that more efficiently crosses the blood-brain barrier, can enhance remyelination. RESULTS/ANTICIPATED RESULTS: In this mouse model, we show a 95% (+/-0.47%, n=3) co-localization of Gamt within mature OL during postnatal (P) day P14 with no co-localization in neurons or other glial cells. This suggests that mature OL are the main cells making creatine in the CNS. Next, we show that knocking out Gamt leads to a significant reduction in OL in the developing corpus callosum, at P14 and P21 (P14: 0.007, n=3; P21: 0.04, n=3). We also show that creatine supplementation causes a trending increase in mature OL density in the corpus callosum following cuprizone demyelination (2% creatine; p=0.052; n=4). Interestingly, cyclocreatine supplementation significantly increased mature OL density in the corpus callosum following cuprizone demyelination (0.1% cyclocreatine; p=0.034; n=4). DISCUSSION/SIGNIFICANCE OF FINDINGS: These studies highlight the important role creatine plays in developmental myelination and remyelination to investigate whether creatine and cyclocreatine provide a therapeutic value during a CNS demyelinating insult. This work investigates a potential therapeutic value of creatine to patients with Multiple Sclerosis.

Revisions to the Common Rule and NIH policy require the use of a single Institutional Review Board (sIRB) for the review of most federally funded, multisite research, with the intent of streamlining the review process. However, since initial implementation in 2018, many IRBs and institutions continue to struggle with the logistics of implementing this requirement. In this paper, we report the findings of a workshop held in 2022 to examine why sIRB review remains problematic and propose possible solutions. Workshop participants identified several issues as major barriers, including new responsibilities for study teams, persistent duplicative review processes, the lack of harmonization of policies and practices across institutions, the absence of additional guidance from federal agencies, and the need for greater flexibility in policy requirements. Addressing these problems will require providing additional resources and training to research teams, the commitment of institutional leaders to harmonize practice, and policymakers to critically evaluate the requirement and provide flexibility in applicability.

OBJECTIVES/SPECIFIC AIMS: Intrahepatic Cholestasis of Pregnancy (ICP) is the most common liver disease unique to pregnancy. Progression of non-alcoholic fatty liver disease (NAFLD) has been linked to the dysregulation of bile acid homeostasis. However, an association of NAFLD with ICP has not been previously evaluated. We evaluated the association between ICP and NAFLD and associated metabolic risk factors, including obesity, dyslipidemia, hypertension, and diabetes. METHODS/STUDY POPULATION: A single-center, retrospective case-control study was conducted between January and December 2017 in a primarily Latina population in a New York City health system with a high prevalence of ICP, 2.53% of all pregnancies (compared to 0.32% nationally). Pearson’s chi-square or Fisher’s exact test and Wilcoxon rank-sum tests were performed to evaluate association of ICP with categorical variables and continuous variables, respectively. Unadjusted odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in comparison with the control group for clinically significant outcomes. RESULTS/ANTICIPATED RESULTS: 149 pregnancies complicated by ICP were identified from electronic medical records; 200 controls were matched by delivery year. Hispanic women were more likely to be diagnosed with ICP than non-Hispanic women (OR 1.90, 95% CI 1.87-3.03). ICP and control patients were similar for: median age (OR 1.02, 95% CI.99-1.06), nulliparity (OR.79, 95% CI.48-1.30) and prevalence of hepatitis C (OR 1.35, 95% CI.08-21.67). In regards to metabolic risk factors, ICP patients and control patients were similar in prevalence of obesity (body mass index>30kg/m^2; OR 1.01, 95% CI.62-1.61), hemoglobin A1c>5.5% (OR.80, 95% CI.34-1.9), total cholesterol >200 mg/dL (OR 4.15, 95% CI.83-20.84), and prevalence of hypertension (OR.69, 95% CI.31-1.52). Median bile acid levels were 30.6 µmol/L (IQR 11.6, 32.7) in the ICP group. ICP patients had higher median alanine aminotransferase (ALT) (32 vs. 16 U/L, p<.0001), alkaline phosphatase (181 vs 128 U/L, p<.0001) and total bilirubin levels (0.5 vs 0.35, p<.0001) compared to controls. ICP patients were more likely to have ALT levels > 50 U/L (2 times the upper limit of normal; OR 3.22, 95% CI 1.48-7.03). ICP patients were significantly more likely to have a history of biliary disease (OR 3.29, 95% CI 1.39-7.80). ICP patients were more likely to have evidence of steatosis on liver imaging (OR 4.69, 95% CI 1.68-13.12) than non-ICP patients. When evaluating a diagnosis of NAFLD based on ICD-10 code or evidence of steatosis on liver imaging, ICP patients were significantly more likely to have a diagnosis of NAFLD than controls (OR 5.7, 95% CI 2.08-15.65). DISCUSSION/SIGNIFICANCE OF IMPACT: ICP appears to be associated with NAFLD independently of metabolic risk factors such as obesity, dyslipidemia, hypertension, and diabetes, suggesting a direct link between NAFLD and ICP. If findings are confirmed, ICP patients, especially those with elevated ALT, would benefit from screening for NAFLD and linkage to liver specialty care postpartum.

Failure to accrue participants into clinical trials incurs economic costs, wastes resources, jeopardizes answering research questions meaningfully, and delays translating research discoveries into improved health. This paper reports the results of a pilot test of the Median Accrual Ratio (MAR) metric developed as a part of the Common Metrics Initiative of the NIH’s National Center for Advancing Translational Science (NCATS) Clinical and Translational Science Award (CTSA) Consortium. Using the metric is intended to enhance the ability of the CTSA Consortium and its “hubs” to increase subject accrual into trials within expected timeframes. The pilot test was undertaken at Tufts Clinical and Translational Science Institute (CTSI) with eight CTSA Consortium hubs. We describe the pilot test methods, and results regarding feasibility of collecting metric data and the quality of data that was collected. Participating hubs welcomed the opportunity to assess accrual efforts, but experienced challenges in collecting accrual metric data due to insufficient infrastructure and inconsistent implementation of electronic data systems and lack of uniform data definitions. Also, the metric could not be constructed for all trial designs, particularly those using competitive enrollment strategies. We offer recommendations to address the identified challenges to facilitate progress to broad accrual metric data collection and use.

North Carolina Central University (NCCU) and Duke Cancer Institute implemented an NCI-funded Translational Cancer Disparities Research Partnership to enhance translational cancer research, increase the pool of underrepresented racial and ethnic group (UREG) researchers in the translational and clinical research workforce, and equip UREG trainees with skills to increase diversity in clinical trials. The Cancer Research Education Program (C-REP) provided training for UREG graduate students and postdoctoral fellows at Duke and NCCU. An innovative component of C-REP is the Translational Immersion Experience (TIE), which enabled Scholars to gain knowledge across eight domains of clinical and translational research (clinical trials operations, data monitoring, regulatory affairs, UREG accrual, biobanking, community engagement, community outreach, and high-throughput drug screening). Program-specific evaluative metrics were created for three broad domains (clinical operations, basic science/lab research, and population-based science) and eight TIE domains. Two cohorts (n = 13) completed pre- and post-surveys to determine program impact and identify recommendations for program improvement. Scholars reported statistically significant gains in knowledge across three broad domains of biomedical research and seven distinct areas within TIE. Training in translational research incorporating immersions in clinical trials operation, biobanking, drug development, and community engagement adds value to career development of UREG researchers.