OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.

In 2017, the NYU Clinical and Translational Science Institute’s Recruitment and Retention Unit created a Patient Advisory Council for Research (PACR) to provide feedback on clinical trials and health research studies. We collaborated with our clinical research informatics team to generate a random sample of patients, based on the International Classification of Diseases, Tenth Revision codes and demographic factors, for invitation via the patient portal. This approach yielded in a group that was diverse with regard to age, race/ethnicity, sex, and health conditions. This report highlights the benefits and limitations of using an electronic health record-based strategy to identify and recruit members for a PACR.

The goal of this study was to assess the utility of participatory needs assessment processes for continuous improvement of developing clinical and translational research (CTR) networks. Our approach expanded on evaluation strategies for CTR networks, centers, and institutes, which often survey stakeholders to identify infrastructure or resource needs, using the case example of the Great Plains IDeA-CTR Network. Our 4-stage approach (i.e., pre-assessment, data collection, implementation of needs assessment derived actions, monitoring of action plan) included a member survey (n = 357) and five subsequent small group sessions (n = 75 participants) to better characterize needs identified in the survey and to provide actionable recommendations. This participatory, mixed-methods needs assessment and strategic action planning process yielded 11 inter-related recommendations. These recommendations were presented to the CTR steering committee as inputs to develop detailed, prioritized action plans. Preliminary evaluation shows progress towards improved program capacity and effectiveness of the network to respond to member needs. The participatory, mixed-methods needs assessment and strategic planning process allowed a wide range of stakeholders to contribute to the development of actionable recommendations for network improvement, in line with the principles of team science.

OBJECTIVES/GOALS: The objectives of the Academy of Community Reviewers (ACR) serve to: (1) provide comprehensive education and training to community members about clinical research and the community review process for clinical research grants; and (2) collaborate with the community in the development of the training to ensure benefice and meaningful engagement. METHODS/STUDY POPULATION: This training targets community members who will serve as future grant reviewers for The Ohio State University Center for Clinical Translational Science (CCTS) pilot grant submissions, other grant submissions and as expert consultants on other projects needing community perspectives. In 2019 and 2020, this training was offered as a live session. Thirty-eight community reviewers were trained and have served as grant reviewers and consultants on over 70 projects. Based on feedback of former graduates, time demands, logistics, and technology advances warranted transitioning the course to an online learning platform. ACR graduates were consulted in course redesign and updates. Course revisions include material on DEIA, implicit bias and health equity in clinical research with narrated lectures. RESULTS/ANTICIPATED RESULTS: Each of the 7 modules (including a total of 15 submodules) will have a brief summary knowledge check. The module “How to incorporate diversity, equity, inclusion and accessibility in health research” will invite trainees to independently explore their own social identity and biases through a guided exercise. The last (7th) module will have interactive opportunities for submitting grant reviews and participation in an online grant review session, geared to The Ohio State University CCTS. ACR graduates have been invited to consult on educational material and pilot the new course. Demographic, knowledge assessments and module evaluations will be collected. An overall course evaluation and focus group interviews with graduates will also be analyzed for quality improvement and contributions in grant reviews. DISCUSSION/SIGNIFICANCE: The increased accessibility of the ACR course will foster more inclusive community engagement and support the development of clinical and translational research that is innovative, efficient, equitable, and relevant to its beneficiaries. This in depth community reviewer training has been designed to be used and customized to other CTSA Hubs.

OBJECTIVES/SPECIFIC AIMS: The goal of this pilot study is to provide a reliable anatomical algorithm for the measurement of adipose tissue within the pelvic cavity as a predictor of prostate cancer aggressiveness and recurrence after radical prostatectomy. METHODS/STUDY POPULATION: We will conduct a retrospective analysis of men treated with radical prostatectomy between 2012 and 2016 at the VA Caribbean Health Care System. Clinical variables, pathology reports, and computed tomography will be reviewed. Pelvic and periprostatic fat (PF) will be measured to determine association between PF and cancer aggressiveness and recurrence. RESULTS/ANTICIPATED RESULTS: We expect a positive association between PF and cancer aggressiveness and recurrence among patients who underwent radical prostatectomy. DISCUSSION/SIGNIFICANCE OF IMPACT: Measurement of subcutaneous and PF within the pelvic cavity can provide a reliable anatomical measure which can be used as a proxy measure to identify those with higher risk of recurrence and develop better prevention and treatment strategies, especially in Hispanic men.

OBJECTIVES/SPECIFIC AIMS: (1) Identify current barriers to coordinated care between behavior consultation and PCIT services. (2) Identify current facilitators to coordinated care between behavior consultation and PCIT services. (3) Utilize this knowledge to create and pilot a coordinated care model that will enhance PCIT and behavior consultation service outcomes. METHODS/STUDY POPULATION: Objectives 1 and 2: Two focus groups consisting of 8–10 behavior consultants will be conducted to gather initial information on barriers and facilitators to coordinated care. Participants will be recruited from the state-funded behavior consultation team, to represent consultation occurring in rural and urban settings. All focus groups will be recorded and transcribed to capture questions and comments. Focus groups will be provided with an initial 10-minute overview of PCIT, including theory, prescribed strategies, and mode of intervention. A grand tour question will then be asked to elicit consultant perceptions of PCIT (e.g., “What are your thoughts on the compatibility between PCIT and behavior consultation services”), followed by probe questions deigned to elicit more detailed information about any perceived differences based on philosophical approach; differences in what is recommended in childcare settings Versus at home, etc.; and perceived barriers to coordinated care between school and outpatient services (e.g., “What factors make coordinating care with outpatient providers challenging?). Participants will be asked about their willingness to participate in a second focus group to review materials created to enhance coordinated care, based on their feedback. Objective 3. Based on feedback from the focus groups and quantitative data regarding factors associated with PCIT outcomes, we will develop an enhanced childcare component(s) for eventual implementation. To confirm our approach, we will invite the members of both focus groups back for a second session, in which we provide them with the created materials and elicit their feedback. We will start with a grand tour question (e.g., “How do you think parents and teachers would react to these materials?”) and then follow-up with probe questions related to feasibility (e.g., “How do you anticipate using these tools?”), appropriateness (e.g., “How adequately do you feel these materials address concerns with coordinated care?”), and acceptability (e.g., “How likely are you to begin using these tools within your consultation?”). Both focus groups will be recorded and transcribed to capture questions and comments. RESULTS/ANTICIPATED RESULTS: (1) Barriers and facilitators to coordinated care will include individual (e.g., acceptability of PCIT framework) and system-level factors (e.g., ease of communication between providers). (2) There will be significant overlap in coordination between the first phase of PCIT (which focuses on positive parenting strategies) and what is prescribed by behavior consultants. (3) There will be less compatibility between the second phase of PCIT (which focuses on disciplinary strategies) and what is prescribed by behavior consultants. (4) A coordinated are model will be rated as more feasible, appropriate, and acceptable to behavior consultants than PCIT services as currently prescribed. DISCUSSION/SIGNIFICANCE OF IMPACT: Childhood disruptive behaviors are among the most frequent reasons for referral to outpatient child/adolescent mental health clinics (Sukhodolsky et al., 2016). Disruptive and aggressive behaviors are problematic, not only for victims of children who are aggressive but also for aggressive children as they age. Although effective treatments exist, families are often provided with conflicting strategies for behavior management by outpatient clinicians and behavior consultants in the daycare setting, thus providing children inconsistent feedback which will delay their attainment of new skills. These data will provide the initial foundation for the development of a coordinated care model that promotes treatment efficacy by improving the compatibility between clinic-based PCIT and daycare-based behavior consultation services.

OBJECTIVES/GOALS: To assess the impact of federal regulations and policies relating to disposable Electronic Nicotine Delivery Systems (ENDS) on youth consumption of these products by identifying factors enabling its growing consumption among youth users and its relation to adolescent addiction to nicotine. METHODS/STUDY POPULATION: Disposable ENDS are all-in-one devices with pre-filled nicotine liquid and a built-in battery. Recent data shows increased sales as users, including youth, are switching from pod-based to disposable ENDS. Thus, an understanding of the regulatory landscape for these products will provide insight on how to mitigate youth nicotine addiction. Data from the Centers for Disease Control and Prevention 2021 National Youth Tobacco Survey (NYTS) was analyzed for patterns of adolescent use. FDA statements and actions involving disposable ENDS companies were reviewed to evaluate the current FDA stance. Analyses of both data sets identified factors enabling the growth in sale of disposable ENDS. RESULTS/ANTICIPATED RESULTS: The NYTS reported 53.7% of youth ENDS users report using disposable ENDS and Puff Bar is the leading ENDS device among youth consumers. In March 2021, Puff Bar announced a return to market with “tobacco-free nicotine” after ceasing sales following an FDA warning letter in July 2020. But synthetic nicotine retains the same chemical properties as tobacco-derived nicotine and the same risks for addiction and abuse. The Food and Drug Administration (FDA) maintains synthetic nicotine products will be regulated on a case-to-case basis, suggesting “closed system devices” containing synthetic nicotine may not be regulated as tobacco products. DISCUSSION/SIGNIFICANCE: The growing popularity of disposable ENDS among youth is problematic. Awareness of strategic regulatory defiance (i.e., Puff Bar), will bring light to industry sales tactics. To develop comprehensive data on disposable ENDS use by young adults, an anonymous survey of college students will be conducted.

OBJECTIVES/GOALS: LGBTQIA2+ patients experience many healthcare inequities and often do not seek healthcare due to stigma andprevioustraumatic experiences in the healthcare system. A paucity of healthcare centersprovidesreduced-fee or free healthcare to LGBTQIA2+ individuals. METHODS/STUDY POPULATION: This project was initiated by the primary author who volunteered at an established student-run free clinic in Columbus, OH. The primary author engaged other students and faculty members, including the co-authors. A needs assessment was conducted by the authors, highlighting the unique needs of LGBTQIA2+ patients in central Ohio. In April 2022, members of the community and volunteer faculty providers established the Rainbow Clinic. The Rainbow Clinic provides primary care services including sexual health/STI testing and gynecology care. The Rainbow Clinic exclusively serves members of the LGBTQIA2+ community in central Ohio and creates a safe and inclusive space to educate medical and nurse practitioner students on the care of LGBTQIA2+ patients in a culturally sensitive way. RESULTS/ANTICIPATED RESULTS: The Rainbow Clinic has provided care for 60 patients equating to 78 visits. Most patients sought care for general primary care (17.9%), gynecological care (11.5%) or STI testing and treatment (7.7%). In addition to medical services, social work services are also provided as part of available mental health services and to provide additional linkage to care. To our knowledge, The Rainbow Clinic is the first student-run free clinic in Ohio to offer pre-exposure HIV prophylaxis (PrEP) medication as well as the required laboratory monitoring. The Rainbow Clinic has ongoing research evaluating patient comfortability throughout their encounters and has launched research studies to evaluate how best to address social determinants of health that affect the health and healthcare of the LGBTQIA2+ community. DISCUSSION/SIGNIFICANCE: The Rainbow Clinic deliversfree healthcareand social work servicesto patients who experience healthcare inequities anddisparities.Additionally, the Rainbow Clinic is a source of education for medical and nurse practitionerstudents to ensure their cultural humility in treating future LGBTQ+ patients.

OBJECTIVES/SPECIFIC AIMS: The goal of the Wake Forest Clinical and Translational Science Institute (WF CTSI) Mentor Academy is to contribute to increasing the next generation of faculty with competencies specific to research mentoring. The curriculum of the Mentor Academy is adapted from an evidence-based national curriculum developed by the National Research Mentoring Network and includes 20 contact hours of didactic and experiential training, complemented with outside readings and assignments. A pre-post-follow-up competency assessment is built in as part of the curriculum for both participants and their current mentees. The purpose of this study was to assess self-rated research mentoring competencies among the Mentor Academy participants to better understand the effectiveness of the Mentor Academy. METHODS/STUDY POPULATION: A total of 37 mid-level or early senior faculty members from WF have participated in the 3 Mentor Academy cohorts that have completed so far. All of the participants receive 5% salary support and are expected to regularly participate in Mentor Academy sessions; complete a pre, post, and 6-month follow-up self-assessments; and provide a list of their active mentees. The identified mentees are also asked to assess the participating mentors’ research mentoring competencies before the start and 6-months after the end of the Mentor Academy. The same list of 26 mentoring competencies are included in the self-assessments for both mentors and mentees. RESULTS/ANTICIPATED RESULTS: The initial results of the self-assessments suggest that mentors are coming into the academy with a rather high self-assessed competency ratings. The change in competency ratings pre/post is not as significant. On average the change in self-assessed competency ratings increases by 1.0 on a 7-point scale. Interestingly enough, for 2 of the cohorts were mentees were also asked to assess their mentors’ competencies, the mentees rated their mentors as having a higher competency (for all 26 items) than what the mentor rated themselves, at both pre and 6-month follow-up assessments. DISCUSSION/SIGNIFICANCE OF IMPACT: After compiling data for 3 different cohorts, we are consistently seeing similar patterns in self-assessed competency ratings; participants are coming in with a high level of competency and an increased level of competency rating by mentees. These findings need to be further considered. For example, the program administrators need to discuss how participants are recruited, if we are recruiting the intended users, and what should we be expecting as an outcome(s) of the program. We also need to further explore different perceptions of mentor-mentee relationships and expectations to see how reliable are the data from mentees. A collaboration with the National Research Mentoring Network is also needed to see how the self-assessed competencies compare to those utilizing their curriculum outside of WF.

OBJECTIVES/GOALS: The goal of this project was to assess the scientific impact of Miami CTSI’s Mentored Career Development (KL2) Program using bibliometric tools and network visualization in addition to the traditional metrics used to provide a comprehensive evaluation. METHODS/STUDY POPULATION: Scholarly productivity of KL2 scholars were tracked using REDCap. For bibliometric data analysis and visualization, publications were queried using iCite (NIH Office of Portfolio Analysis) and Web of Science database. A total of 173 publications produced by eight KL2 scholars from 2013-2018 were analyzed and categorized into pre-award, during award, and post-award periods. iCite was used to assess scientific influence and translation. Scientific networks and collaboration were visualized using VOSviewer (Centre for Science and Technology Studies, Leiden University). CTSA Common Metrics were tracked using the Results Based Accountability framework. RESULTS/ANTICIPATED RESULTS: Albeit of modest size, the Miami CTSI’s KL2 Program had significant scientific productivity and impact in its first five years. Our KL2 scholars’ publications were cited twice as frequently as other papers in their fields. Further, 48% of publications post KL2 award were above the NIH 50th percentile and had higher citation impact compared to the average NIH-funded paper; 11% were in the top 10% NIH citation ranking. In contrast, only 20% of the publications pre-KL2 award were above the NIH 50th percentile. The program also promoted research collaboration; network visualizations indicate larger co-authorship and organization networks of KL2 scholars post-award. DISCUSSION/SIGNIFICANCE OF IMPACT: Bibliometric and data visualization approaches helped us better identify trends and gauge effectiveness of the KL2 program. These findings provided useful insight into the scientific influence and impact of our scholars’ work.

OBJECTIVES/GOALS: Social distancing practices during COVID-19 may impact experience of stress, substance use and violence exposure. This study aims to describe the effect of the COVID-19 stay-at-home orders on stress, substance use, and teen dating violence (TDV) among young women living in Baltimore City. METHODS/STUDY POPULATION: Study participants were recruited from an observational study examining TDV before the COVID-19 pandemic, through snowball sampling, pediatric and adolescent primary care clinics, the pediatric emergency department, and a registry for patients interested in participating in COVID-19 research. Participants were between the ages of 16 and 22, identified as female, and lived in Baltimore, Maryland. They were asked to complete a baseline survey. March 16, 2020 (Maryland governor’s stay-at-home order) through June 2022 defined the COVID-19 pandemic period. The survey assessed stress experiences, including isolation, finances, job loss, transportation, school stress, substance use, experiences of violence and adherence to COVID-19 safety measures. We conducted descriptive and bivariate analyses. RESULTS/ANTICIPATED RESULTS: Participants (n=105) had a mean age of 19.4 years (SD 1.73). Preliminary analyses demonstrate that stress associated with isolation, finances, transportation, and school increased during the pandemic compared to pre-pandemic. In addition, the majority of participants who used marijuana, e-cigarettes, and alcohol used about the same amount or more of each substance during the pandemic. For the next steps, we will examine experiences of TDV for young women during the pandemic and examine whether experiences of TDV differ for young women who reported a greater adherence to COVID-19 safety measures compared to participants who adhered less. DISCUSSION/SIGNIFICANCE: Assessing the impact of COVID-19 safety measures on stress, substance use, and TDV is critical to informing and designing future public health interventions. In addition, the information obtained from this study may be used to address the unique challenges faced by disenfranchised populations while curbing the spread of infectious diseases.

Objectives/Goals: The demands on MICHR’s Evaluation team are profuse and varied. Quarterly team meetings were used to keep track projects, identify new projects, and relay important new initiatives from MICHR leadership. The MICHR Translational Innovation team took on the task of assessing the Evaluation team’s processes to design better workflow and effectiveness. Methods/Study Population: The process included 5 stages, Empathize, Define, Ideate, Prototype and Test. Sixteen interviews were conducted with MICHR faculty and staff. Interviews were coded and summarized. Seventeen themes were mapped and distilled into 5 key insights. From the key insights, design principles were identified to guide a design session with Translational Innovation staff and Evaluation staff. New work processes were proposed, designed, and tested by both teams. The Evaluation team “test-drove” the prototype and iterative design sessions were conducted to determine which new elements were successful. The Evaluation team was positioned to begin utilizing the newly designed process at the beginning of MICHR’s new grant year. Results/Anticipated Results: The MICHR Evaluation team is instrumental to the development, conduct, and dissemination of Clinical & Translational Science (CTS), a primary objective of MICHR’s work. Three types of evaluation projects were identified through the design process: required reporting, CQI/program improvement, and CTS/impact evaluation. The service design process enabled the Evaluation team, and MICHR program leads to better identify and prioritize collaborations between the Evaluation and program teams that improved the quantity and quality of MICHR CTS outputs. Discussion/Significance of Impact: Generating CTS is critical to the missions of NCATS and MICHR. Thoughtfully designing processes that facilitate and increase CTS output that can be shared and duplicated across the consortium is invaluable.

OBJECTIVES/SPECIFIC AIMS: Inflammatory bowel disease (IBD) patients are at an increased risk of Clostridium difficile infection (CDI) but the impact of CDI on disease severity is unclear. The aim of this study was to determine the effect of CDI on long-term disease outcome in a cohort of IBD patients. METHODS/STUDY POPULATION: We analyzed patients enrolled in a prospective IBD natural history registry. Patients who tested positive at least once formed the CDI positive group. We generated a 2:1 propensity matched control cohort based on risk factors of CDI in the year before infection. Healthcare utilization data (emergency department use, subsequent hospitalizations, telephone encounters), medications, labs, disease activity, and quality of life metrics were temporally organized. RESULTS/ANTICIPATED RESULTS: A total of 198 patients (66 CDI, 132 matched controls) were included [56.6% female; 60.1% Crohn’s disease (CD), 39.9% ulcerative colitis (UC)]. Groups were not significantly different in the year before infection in all metrics but in the year of infection, having CDI was significantly associated with more steroid and antibiotic exposure, elevated C-reactive protein or erythrocyte sedimentation rate, and low vitamin D (all p<0.01). Infection was associated with increased disease activity metrics (UC: p=0.036, CD: p=0.003), worse disease-related quality of life (p=0.003), and increased healthcare utilization (p<0.001). In the next year after infection those with prior CDI continued to have increased exposure to vancomycin or fidaxomicin (p<0.001) and all other antibiotics (p=0.01). They also continued to have more clinic visits (p=0.006), telephone encounters (p=0.001), and worse disease-related quality of life (p=0.03), but disease activity and biomarkers of severity were not significantly different between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: CDI infection in IBD is significantly associated with various surrogate markers of disease severity, increased healthcare utilization and poor quality of life during the year of infection. CDI patients continue to experience poor quality of life after infection with increased clinic visits and antibiotic exposure while disease activity is no longer significantly increased. These findings suggest that CDI infection may have a lasting effect on healthcare utilization beyond the acute treatment period.

OBJECTIVES/SPECIFIC AIMS: This study will use face-to-face interviewers with Medicare-eligible stroke survivors, and adult caregivers of stroke survivors, to extend the aims of a quantitative study on healthcare utilization in elderly stroke survivors. The objective of this research is to better understand, in more detail, relevant barriers and facilitators to accessing healthcare among older stroke survivors. The ultimate goal of this research is to develop strategies to improve access to healthcare, such as home modifications; changes to the neighborhood physical environment; or interventions at the provider/service level. This research will also serve as a precursor for future intervention work that will be proposed as a part of a K01 proposal. METHODS/STUDY POPULATION: Participants were recruited from Ann Arbor and Flint, MI using an existing academic-community partnership as well as through the University of Michigan Stroke Clinic. A total of 8–10 stroke survivors and 1–2 caregivers were recruited through the partnership and clinic records, as well as some use of snowball sampling to obtain a socially, economically, and racially representative sample. Participants must be 65+ years old, eligible for Medicare, living in the community, identify as either White or Black, and have no major cognitive/language deficits that jeopardize informed consent. Face-to-face interviews were conducted, and open-ended questions emphasized environmental barriers and facilitators to accessing healthcare, with a focus on social and physical barriers in the home and neighborhood. Interviews were audio recorded and transcribed, and field notes from 1 to 2 sources were also documented and will be used to triangulate the data and increase coding validity. Audio recordings will be reviewed multiple times and quotes relevant to the research questions and underlying theoretical framework will be transcribed verbatim. The transcripts will be analyzed using thematic coding based on literature and the study objectives and hypotheses. I will identify primary themes related to environmental barriers and facilitators to accessing healthcare among the stroke-survivors. RESULTS/ANTICIPATED RESULTS: Preliminary results suggest that participants are primarily concerned about the social environment. Several interviews revealed that stroke survivors felt socially isolated and were often hesitant to ask for help because they did not want to be a burden on their family and friends. Transportation to appointments was also identified as a barrier due to the fact that many people are no longer able to drive, yet are not comfortable navigating other forms of transportation. We expect to identify additional physical and social environmental challenges to both health care utilization and well-being more generally, among older stroke survivors. Anticipated themes may include: barriers in the physical environment such as transportation to care and services, social support and social environmental factors to support feeling safe leaving home to access care. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite the physical and economic burden of stroke, and attempts to improve outcomes for stroke survivors living in the community, stroke survivors have high rates of disability and unmet medical and psychological needs. The results from this research are anticipated to directly inform future partnerships and intervention in these, or in similar communities. Understanding how the environment influences access to healthcare for elderly stroke survivors is essential if we want to increase recommended preventative care and treatment in this vulnerable population with unique healthcare needs. The results of this study will be used to directly inform the aims and methods for other translational research projects, including a K01 proposal, in which I will develop and pilot a community-based intervention to ameliorate environmental barriers and enhance facilitators of access to healthcare for older, disabled adults.

OBJECTIVES/GOALS: Review all approved companion diagnostics (CDxs) labeling for therapeutic class language. Examine the regulatory pathways of CDx products whose labels contain therapeutic class labeling. Develop recommendations for pharmaceutical industry professionals on best practices in the co-development of CDxs and oncology therapeutic products. METHODS/STUDY POPULATION: Literature discussing companion diagnostics was reviewed from EBSCOhost, PubMed, and OVID. The Intended Use language within CDx labels on the Food and Drug Administrations “List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools)” website were reviewed on November 1, 2021 for therapeutics class language. For CDx products with therapeutic class label language, the regulatory history was evaluated to determine the development approach taken to achieve the language. RESULTS/ANTICIPATED RESULTS: A total of 45 CDxs were identified, of which only 2 contained therapeutic class labeling, both of which were devices for the identification of epidermal growth factor receptor (EGFR) mutations for the treatment of non-small cell lung cancer (NSCLC). Three additional EGFR CDxs were approved; however, they did not contain therapeutic class labeling. The first CDx was the Cobas EGFR Mutation Test V2, which received therapeutic group label language as an update on October 27, 2020; however, prior to the therapeutic class labeling, three oncology products were named in the Intended Use: Tarceva (erlotinib), Tagrisso (osimertinib), and Iressa (gefitinib). The second CDx to incorporate therapeutic class labeling was the ONCO/Reveal Diagnostic Lung and Colon Cancer Assay upon initial approval on July 30, 2021. DISCUSSION/SIGNIFICANCE: EGFR CDxs are the first to shift towards therapeutic class labeling. Indication, molecular alterations, and mechanism of action of the approved therapeutic class products, number of products approved, as well as CDx analytical and clinical validation influence class label relevance. Discussions with the FDA are encouraged early in development.

ABSTRACT IMPACT: This work will inform the ongoing development of adaptive capacity and preparedness of the CTSA Program and other clinical and translational research organizations in their quest of improving processes that drive outcomes and impacts, shaping effective programs and services, and strengthening their emergency readiness and sustainability. OBJECTIVES/GOALS: -Share the progress and preliminary findings of an ‘Adaptive Capacity and Preparedness of CTSA Hubs’ CTSA Working Group; -Improve our awareness and understanding of the efficient and effective changes helping CTSA hubs build robust capacity to address METHODS/STUDY POPULATION: A multi-case study including: - Triangulating multiple sources of information and mixed methods (survey/interviews of research administrators, researchers, evaluators, and other key stakeholders), literature review, document and M&E system information analysis, and expert review; - Describing CTSA hubs’ experiences as related to research implementation, translation, and support during the time of emergency; - Administering a comprehensive survey of the CTSAs addressing their challenges, lessons learned, and practices that work in various program components/areas. Data collection includes aggregate and cross-sectional data, with representation based on CTSA size, maturity, and population density. RESULTS/ANTICIPATED RESULTS: The described approach shows sound promise to investigate and share strategies and best practices for building adaptive capacity and preparedness of CTSAs -- across various scientific sectors, translational research spectrum, and the goals outlined by NCATS for the CTSA program. The anticipated results of this research will include the identified/shared innovative solutions and lessons learned for this rapidly emerging, high-priority clinical and translational science issue. ‘High-quality lessons learned’ are those that represent principles extrapolated from multiple sources and triangulated to increase transferability to new contexts and situations. DISCUSSION/SIGNIFICANCE OF FINDINGS: The project provides useful knowledge and tools to research organizations and stakeholders across multiple disciplines -- for mitigating the impact of the COVID-19 disaster via effective adjusting programs, practices, and processes, and building capacity for future successful, ‘emergency ready and responsive’ research and training.