Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.

OBJECTIVES/GOALS: Low-dose aspirin is an established treatment to prevent preeclampsia, a leading cause of maternal and perinatal complications. Nevertheless, aspirin failure is not uncommon. We are investigating whether a gain-of-function genetic polymorphism in a platelet thrombin receptor is associated with aspirin failure in the prevention of preeclampsia. METHODS/STUDY POPULATION: Women who had preeclampsia in an initial pregnancy who then received low-dose aspirin in a subsequent pregnancy will be evaluated. We will compare between women who developed preeclampsia despite aspirin (aspirin non-responders) to women who did not develop preeclampsia with aspirin treatment (aspirin responders). Specifically, we will evaluate the allelic frequency of a single nucleotide variant (rs773902) in PAR4 thrombin receptor on platelets. This variant is associated with increased platelet function and potentially aspirin resistance. In addition, we will analyze the platelet response to PAR4 activation before and 1 hour after administering a single 81 mg enteric-coated aspirin tablet. RESULTS/ANTICIPATED RESULTS: We hypothesize that the prevalence of the PAR4 variant will be significantly higher among women who had recurrence of preeclampsia despite aspirin therapy. We also postulate that women who developed preeclampsia despite aspirin prophylaxis and have the polymorphism will have increased platelet aggregation in response to activation of PAR4, either by thrombin or peptides that activate the receptor, both at baseline and 1 hour after aspirin administration. DISCUSSION/SIGNIFICANCE: If our hypothesis that aspirin failure in preeclampsia prevention is associated with the gain-of-function polymorphism in the platelet PAR4 thrombin receptor, there may be justification for additional experimental studies to assess whether better pregnancy outcomes can be obtained by targeting thrombin itself using low molecular weight heparin.

The ability to effectively lead an interdisciplinary translational team is a crucial component of team science success. Most KL2 Clinical Scholars have been members of scientific teams, but few have been team science leaders. There is a dearth of literature and outcome measures of effective Team Science Leadership in clinical and translational research. We focused our curriculum to emphasize Team Science Leadership, developed a list of Team Science Leadership competencies for translational investigators using a modified Delphi method, and incorporated the competencies into a quantitative evaluation survey. The survey is completed on entry and annually thereafter by the Scholar; the Scholar’s primary mentor and senior staff who educate and interact with the Scholar rate the Scholar at the end of each year. The program leaders and mentor review the results with each Scholar. The survey scales had high internal consistency and good factor structure. Overall ratings by mentors and senior staff were generally high, but ratings by Scholars tended to be lower, offering opportunities for discussion and career planning. Scholars rated the process favorably. A Team Science Leadership curriculum and periodic survey of attained competencies can inform individual career development and guide team science curriculum development.

Implementation of clinically useful research discoveries in the academic environment is challenged by limited funding for early phase proof-of-concept studies and inadequate expertise in product development and commercialization. To address these limitations, the National Institutes of Health (NIH) established the National Centers for Accelerated Innovations (NCAI) program in 2013. Three centers competed successfully for awards through this mechanism. Here, we present the experience of one such center, the Boston Biomedical Innovation Center (B-BIC), and demonstrate its remarkable success at the translation of innovations to clinical application and commercialization, as well as skills development and education.

ABSTRACT IMPACT: Our implementation model translates two evidence-based nutritional and behavioral interventions to lower blood pressure, into a community-based intervention program for seniors receiving congregate meals. OBJECTIVES/GOALS: The Rockefeller University, Clinical Directors Network, and Carter Burden Network received an Administration for Community Living Nutrition Innovation grant to test whether implementation of DASH-concordant meals and health education programs together lower blood pressure among seniors aging in place. METHODS/STUDY POPULATION: n=200, >60 yr, >4 meals/week at CBN; engagement of seniors/stakeholders in planning and conduct; Advisory Committee to facilitate dissemination; menus aligned with Dietary Approaches to Stop Hypertension (DASH) and NYC Department for the Aging nutritional guidelines; interactive sessions for education in nutrition, BP management, medication adherence. Training in use of automated daily home BP monitors (Omron 20). Validated surveys at M0, M1, M3, M6. Taste preference and cost assessed through Meal Satisfaction (Likert scale) and Plate Waste measures. Primary Outcome: Change in Systolic BP (SBP) at Month 1; change in %BP controlled. Secondary: validated cognitive, behavioral, nutritional measures (SF-12, PQH-2), economics; staff/client satisfaction, trends and significant associations. RESULTS/ANTICIPATED RESULTS: n=94, x2 age =73 +/- 8 years, 65% female, 50% White, 32% Black/African American, 4% Asian, 1% American Indian, Alaskan Native, 13% Other, 32% Latino/a, 43% with income <$20,000. Mean SBP at Baseline was 137.87 +18.8 mmHg (range 98-191). Menus were adapted to provide 20% daily DASH requirements at breakfast, 50% at lunch. Participants attended classes in nutrition and medication management and were provided with and trained to use an automated home BP monitor. Meal satisfaction scores dipped briefly then met or exceed pre-DASH levels. Home BP data was downloaded every 2-4 weeks with social/behavioral support. The COVID-19 closures interfered with BP outcome data collection and meal service ceased. Primary outcome: x2 change in SBP at Month 1 = -4.41 mmHg + 18 (n=61) (p=0.713). Significant associations will be reported. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our community-academic research partnership implemented the DASH diet in congregate-meal settings to address uncontrolled hypertension in seniors. COVID-19 interrupted the study, but encouraging trends were observed that may inform refinement to this community-based health intervention for seniors.

OBJECTIVES/GOALS: Irreproducible and incompletely reported research lead to misallocated resources, wasted effort in pursing inappropriate avenues of investigation, and loss of public trust. To address this challenge, we employed a Team Science approach to create a multi-modal program to support Rigor, Reproducibility, and Reporting in Translational Science. METHODS/STUDY POPULATION: We conducted literature searches to reveal sources of irreproducibility and recommended corrective actions, invited leaders in the field to give lectures on opportunities to support reproducible science, and worked with the Rockefeller team science leadership group to instill an overarching rigor approach, infused into all training efforts. This multifaceted program was labeled R3 (R-cubed) for Enhancing Scientific Rigor, Reproducibility, and Reporting. RESULTS/ANTICIPATED RESULTS: Didactic Courses:

• Introduction to Biostatistics and Critical Thinking – focus on pitfalls in inferential statistics, consequences of poor research, and errors in published research.

• Scientific Writing – teaches methods and procedures in writing to ensure reproducibility. Lecture Series

• Established nine lectures on topics related to R3, including Data Management, Statistical Methods, Genomic Analyses, Data Repositories, Data Sharing, Pharmacy Formulation, and e-lab notebooks. Website

• Creating a comprehensive website as repository for research, methods, programs, updates, and improvements related to R3. KL2 Clinical Scholars Seminars and Navigation

• Scholars participate in seminars and tutorials to discuss opportunities to improve R3 across the research life-course.

DISCUSSION/SIGNIFICANCE OF IMPACT: Striving for research reproducibility takes focused energy, discipline, and vigilance, but the effort is worthwhile as rigorous and reproducible science is the prerequisite for successful translation of great discoveries into improved health. CONFLICT OF INTEREST DESCRIPTION: none

OBJECTIVES/GOALS: We have developed a comprehensive Translational Research Navigation Program to guide investigators all the way from protocol development through study closure. As the program evolved, we initially developed organizational tools and then restructured them into a series of checklists to ensure that critical elements were not excluded or duplicated. METHODS/STUDY POPULATION: A series of checklists to assure that all research elements, including regulatory, scientific, and institutional, are addressed from protocol inception through study closure were developed by clinical research coordinators/navigators. The checklists are periodically updated and modified to reflect changing local and national regulations and policies. The first tool became the “Protocol Development Checklist” and then additional tools were developed and modified into a suite of navigation checklists that include “Protocol Implementation Checklist,” “Protocol Conduct Checklist,” and “Protocol Completion Checklist.” RESULTS/ANTICIPATED RESULTS: The checklists have been incorporated into the Translational Research Navigation Program and have enhanced the organization and quality of protocols throughout their lifespan. For example, implementation of the Protocol Development Checklist resulted in a reduction in time to IRB approval (currently 10 days), and implementation of the Protocol Implementation Checklist has impacted the time from IRB approval to study start-up. The Protocol Conduct Checklist has aided investigators in being better prepared and more organized for study conduct activities and the Protocol Closure Checklist has assured timely protocol closure and regulatory compliance, including reporting to ClinicalTrials.gov. DISCUSSION/SIGNIFICANCE OF IMPACT: Protocol checklists are powerful tools to enhance thoroughness, organization, and quality of the clinical research process. The Rockefeller University protocol checklists are available to the CTSA and Scientific Communities. CONFLICT OF INTEREST DESCRIPTION: NA.

OBJECTIVES/GOALS: To facilitate the development of innovative injection products by providing translational researchers with a regulatory and manufacturing road map for producing small batch sterile products for Phase 1 research use. To leverage recent AMC investments in facility improvements and pharmacy training in the areas of sterile product production, testing, and environmental controls, that can be used to support production of phase 1 clinical trial supplies METHODS/STUDY POPULATION: Searching and organizing relevant data and information from web portals and databases in the following: areas: FDA, EMA, USP regulations, regulatory science, pharmaceutical formulation and analytics, supply vendors, analytical testing laboratories, and product testing laboratories. Present the information using a user friendly format including flow charts and development timelines, taking the perspective of the translational investigator. RESULTS/ANTICIPATED RESULTS:

• Choosing AMC resources vs outside consultants and vendors, leveraging local resources where possible

• Qualifying and monitoring suppliers, testing laboratories, in-house departments, and Contract Drug Manufacturing Organizations (CDMO)

• Bringing together the deliverables for the IND CMC section

• Where and how to leverage available products and science to simplify safe and reliable production

DISCUSSION/SIGNIFICANCE OF IMPACT: Use and utility of injectable drug products, both small molecule and biologics, is growing rapidly, and is projected to continue to escalate well into the next decade. This is due not only to advances in medicine, but also to improvements in AMC-based sterile product production, and a better understanding of small batch manufacturing methods. All three trends align in academic medical centers (AMC) and can be utilized by translational researchers, if they can understand the potential and regulatory requirements.

OBJECTIVES/GOALS: To describe principles, best practices, and techniques recommended to instill deep understanding of the application and interpretation of statistical techniques and statistical inference among translational scientists and trainees, that best support the concepts of scientific Rigor, Reproducibility and Reporting. METHODS/STUDY POPULATION: Each of the six New York City Area Biostatistics, Epidemiology and Research Design (BERD) resources have strong educational programs, novel curricular components, and creative strategies, implemented by award winning educators. To capitalize on shared knowledge, innovation, and resources, the six teams formed the New York City Area BERD Collaborative (NYC-ABC) comprised of BERD resources from Mt. Sinai, Cornell, Einstein, Columbia, Rockefeller, and NYU. The collaborative suggests principles, concepts, tools and approaches to support the concepts of scientific Rigor, Reproducibility and Reporting in translational science. RESULTS/ANTICIPATED RESULTS: Principles:

• Value of team science approach and including biostatisticians early and often.

• Carefully designing experiments to reduce bias and increase precision.

• Trainees’ focus is often on “statistical significance” and the p-value. Consequences of data dredging/p-hacking, and the impact of sample size and other factors on statistical significance.

• Emphasizing the effect size and answering the scientific hypothesis when reporting results.

• Statistical code used to produce results should be well annotated and raw data posted online to enhance reproducibility.

• Incorporate effective multiple modalities (i.e. didactic, demonstrative, hands on workshops, applications, and tools).

• Approach from “the drivers’ seat” perspective, rather than strictly mathematical.

• Endorse flipped classroom approach

DISCUSSION/SIGNIFICANCE OF IMPACT: Like any complex discipline, biostatistical education can be approached from several dimensions, but it remains essential to focus on fundamental goals of science. We remind our trainees that the goal of science is to create knowledge, not to “find significance”. Deep understanding of inferential methods and proper interpretation of results are key. CONFLICT OF INTEREST DESCRIPTION: None.

OBJECTIVES/GOALS: Innovations with positive health impact are a high priority for NCATS and CTSAs. Program design that uses the Causal Pathway approach incorporates performance indicators that assess impact. We applied Causal Pathway thinking to an ongoing national program to enhance the evaluation of program impact. We report Lessons Learned. METHODS/STUDY POPULATION: We conducted a day-long onsite workshop to introduce the model to the project team, build capacity, and map the existing program elements to Logic Models representing program Specific Aims. A local Causal Pathway (CP) champion was identified. Alignment of the Logic Models with the CP approach (input→activities→ outputs→effects/impact) developed iteratively through biweekly, then monthly conferral among stakeholders. Key tasks included distinguishing among activities, outputs, and effects (impacts), and identification of performance indicators for each stage of the Causal Pathway. Visualization tools and an additional late stage half-day workshop were used to foster consensus. Implementation of the CP model tested the feasibility of collecting specific indicators and prompted model revisions. RESULTS/ANTICIPATED RESULTS: Program leadership and team members (n = 30) participated in the kick-off workshop. Four Specific Aims were mapped to Logic Models. Multiple Causal Pathway (CP) diagrams, one for each project in the program, were developed and mapped to Aims. Alignment of CP threads to Aims and identification of performance indicators required iteration. CP threads converged onto common final Impacts, sometimes crossing to another Aim. Performance indicators for operations were readily accessible to team members, and less so for impacts. Assumptions about program effects were subjected to specific indicators. Over time, Leadership noticed more expression of CP thinking in daily activities. New projects developed during this period incorporated the CP approach. Teams were able to streamline and simplify Logic/CP models. DISCUSSION/SIGNIFICANCE OF IMPACT: Through capacity-building and mentored exercises, an innovation team was able to infuse CP thinking into the evaluation of their ongoing program. The CP approach to design and evaluation maps progress and indicators across the life of a program from initial activities to its ultimate impact.

OBJECTIVES/GOALS: There is universal recognition of the importance of team science and team leadership. We have developed a semi-quantitative translational science specific team leadership competency assessment tool and have begun implementation studies to assess the impact of personalized feedback on the team science leadership skills of KL2 Clinical Scholars. METHODS/STUDY POPULATION: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to concretize the relevant constructs, then used these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively create domain-specific survey items. Further discussion helped refined the number, grouping, and wording. Scholars also contributed feedback in item development. We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars, and having each Scholar rate themselves. Each item was answered using a six-point Likert scale where a low score indicated poor expression and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Incorporation into a REDCap data base made consenting and rating process by TSE’s and the Scholars straightforward. The a priori domains (Foundational Leadership Competencies, Professionalism, Team Building and Team Sustainability, Appropriate Resource Use and Study Execution, and Regulatory Accountability) had high internal validity and good internal factor structure. The congruence between TSE and Scholar self-ratings were uniformly high, and discordance was often a function of “confidence” and “modesty” on the part of the scholar, rather than deficiency. Supporting comments were informative about performance barriers and mechanisms for improvement. Return of results allowed for the exploration of training gaps. Scholars were surveyed to gauge their reaction to the formal feedback. DISCUSSION/SIGNIFICANCE OF IMPACT: This quantification of team science leadership constructs has allowed for A)- the articulation of constructs essential for successful Translational Scientists to acquire during their training, B)- identification of gaps in that training and skill set, and C)- mechanisms for bolstering any identified gaps in these essential leadership constructs. CONFLICT OF INTEREST DESCRIPTION: None

OBJECTIVES/SPECIFIC AIMS: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to help concretize the relevant constructs, and then usied these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively creating domain-specific survey items, and then further discussed and refining the number, grouping, and wording of the items. METHODS/STUDY POPULATION: We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars. Each item was answered using a six-point Likert scale where a low score indicated poor expression of the specific leadership attribute and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Means, medians, standard deviations, and ranges of each item were calculated and tabulated. A complete (Pearson) correlation matrix was computed so that the raw inter-item relationships can be observed. For each a priori Domain an equal weighted summary scale was created and tabulated for review. The internal consistency of each a priori scale was assessed by calculating Cronbach’s Alpha (α). Items with low Item to Construct coefficients were candidates for elimination or modification, and overall scales with low’s will undergo further discussion. To challenge our assumptions of the construction and integrity of each domain, we employed exploratory Principal Components Analysis (PCA), followed by orthogonally rotated Factor Analysis (FA). We also forced the PCA / FA analysis to extract the a priori dimensions that allowed us to compare if the empirical and a priori structures match. DISCUSSION/SIGNIFICANCE OF IMPACT: We are partnering with the CTSA programs at Penn and Yale to assess issues of generalizability and scalability. We are working with Vanderbilt to install survey onto REDCap for ease of dissemination. Will continue to assess psychometric properties and refine as we receive more input.

OBJECTIVES/SPECIFIC AIMS: To develop a KL2 curriculum on the science and art of drug formulation. METHODS/STUDY POPULATION: Develop training materials for KL2 scholars that outline the art of formulation development. Materials will include syllabi, reading materials, and course work. RESULTS/ANTICIPATED RESULTS: This will enhance the training of KL2 scholars by incorporating formulation development concepts into their human health enhancing research projects. DISCUSSION/SIGNIFICANCE OF IMPACT: For new chemical entities, formulation goals must be realistic and move along in a step-wise manner from the laboratory bench, through toxicology studies, and on to Phase 1 studies. By training scholars in phase-specific formulation goals, their interactions with funding agencies, formulation scientists, and regulators will be more efficient, productive, and successful. For those scholars who are working to improve existing treatments, introducing the concept of formulation improvements that can create new indications, or improve efficacy, safety and patient compliance will open up more possibilities for creative product development.

Dietary fatty acid (FA) composition may influence metabolism, possibly affecting weight management. The purpose of this study was to compare the effects of a 5-d diet rich in PUFA v. MUFA. A total of fifteen normal-weight men participated in a randomised cross-over design with two feeding trials (3 d lead-in diet, pre-diet visit, 5-d PUFA- or MUFA-rich diet, post-diet visit). The 5-d diets (50 % fat) were rich in either PUFA (25 % of energy) or MUFA (25 % of energy). At pre- and post-diet visits, subjects consumed breakfast and lunch test meals, rich in the FA for that 5-d diet. Indirect calorimetry was used for 4 h after each meal. There were no treatment differences in fasting metabolism acutely or after the 5-d diet. For acute meal responses before diet, RER was higher for PUFA v. MUFA (0·86 (sem 0·01) v. 0·84 (sem 0·01), P<0·05), whereas diet-induced thermogenesis (DIT) was lower for PUFA v. MUFA (18·91 (SEM 1·46) v. 21·46 (SEM 1·34) kJ, P<0·05). After the 5-d diets, the change in RER was different for PUFA v. MUFA (−0·02 (sem 0·01) v. 0·00 (sem 0·01), P<0·05). Similarly, the change in fat oxidation was greater for PUFA v. MUFA (0·18 (sem 0·07) v. 0·04 (sem 0·06) g, P<0·05). In conclusion, acutely, a MUFA-rich meal results in lower RER and greater DIT. However, after a 5-d high-fat diet, the change in metabolic responses was greater in the PUFA diet, showing the metabolic adaptability of a PUFA-rich diet.