Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.

In February 2023, 52 cases of gastrointestinal illness were reported in customers of Takeaway A, South Wales. Shigella flexneri serotype 2a was the causative organism. An outbreak investigation was conducted to determine the extent and vehicle of the outbreak.

Following descriptive summary and environmental investigations, a case–control study was completed. Participants completed a telephone questionnaire on food, travel, and environmental exposures. A multivariable logistic regression model was built, including exposures with p-values < 0.2 and interactions identified on stratified analysis. Staff faecal samples were screened for Shigella sp.

Thirty-one cases and 29 controls were included in the study. Eighty-seven per cent of cases and 76% of controls ate from Takeaway A on 10 February 2023. Coleslaw was the main factor associated with illness (aOR: 200, 95% CI: 12–3220) and an interaction with cabbage was identified (aOR: 886, 95% CI: 26–30034). Shigella sp. were not detected in any staff samples.

Coleslaw was the most likely vehicle. Though the contamination route is unknown, a food handler is the most likely source. This large outbreak differs from recent European outbreaks, which primarily have been associated with sexual transmission. Although uncommon in the UK, S. flexneri should be considered as a cause of foodborne outbreaks.

Coastal landforms and associated archaeological records are at risk of erosion from a combination of rising sea levels and increasingly frequent high-intensity storms. Improved understanding of this risk can be gained by braiding archaeological and geomorphological methodologies with Indigenous knowledge.1 In this article, archaeological, geomorphological and mātauranga (a form of Indigenous knowledge) are used to analyse a prograded Holocene foredune barrier in northern Aotearoa/New Zealand. Anthropogenic deposits within dune stratigraphy are radiocarbon-dated and used as chronological markers to constrain coastal evolution, alongside geomorphological analyses of topographic data, historical aerial photographs and satellite imagery. These investigations revealed that the barrier is eroding at a rate of 0.45 m/year. A midden in the foredune, which has been radiocarbon dated to 224–270 B.P. (95% Confidence), has been exposed by coastal erosion, confirming that the barrier is in the most eroded state it has been within the past ~300 years. Vertical stratigraphy reveals the presence of midden and palaeosol deposits capped by dune sand deposits in the foredune, indicating that vertical accretion of the foredune continued over the last ~200 years, despite the barrier now being in an eroding state. Mātauranga played a vital role in this project, as it was the coastal taiao (environmental) monitoring unit of Patuharakeke (a Māori sub-tribe) that discovered the midden. The ecological mātauranga shared also played a vital role in this project, adding experiential evidence to empirical observations. The work of local Indigenous groups, like Patuharakeke, demonstrates the active use of mātauranga, woven with Western science methods to preserve or capture the knowledge contained within archaeological sites at risk of being lost to coastal erosion. In this study, we present a method for weaving mātauranga, geomorphological and archaeological approaches to gain a deeper understanding of coastal landscape development.

OBJECTIVES/GOALS: Empowering the Participant Voice (EPV) is a 6-CTSA Rockefeller-led collaboration to developcustom REDCap infrastructure to collect participant feedback using the validated Research Participant Perception Survey (RPPS), demonstrate its value in use cases, and disseminate it for broad adoption. METHODS/STUDY POPULATION: The EPV team developed data and survey implementation standards, and specifications for the dashboard and multi-lingual RPPS/REDCap project XML file. The VUMC built a custom At-a-Glance Dashboard external module that displays Top Box scores (percent best answer), with conditional formatting to aid analysis, and response/completion rates. Results populate site dashboards, and aggregate to a multi-site dashboard for benchmarking. Results can be filtered by participant/study characteristics. Sites developed individual use cases, leveraging local infrastructure, initiatives and stakeholder input. Infrastructure and guides were designed for dissemination through public websites. RESULTS/ANTICIPATED RESULTS: Five sites sent 23,797surveys via email, patient portal or SMS. 4,133 (19%) participants diverse in age, race, and ethnicity, returned responses. Sites analyzed their data and acted on selected findings, improving recruitment, communication and feeling valued. Aggregate scores for feeling listened to and respected were hight (>90%%); scores for feeling prepared by the consent process were lower (57-77%) and require action. Some groups experiences were better than others. Sites differed significantly in some scores. Dissemination of EPV is underway. Infrastructure and guides are downloadable free of charge, with advice from the EPV team. In 2023, a sixth site began piloting a lower literacy survey version and syncing data to the consortium dashboard. DISCUSSION/SIGNIFICANCE: The EPV RPPS/REDCap infrastructure enabled sites to collect participant feedback, identify actionable findings and benchmark with peers. Stakeholders and collaborators designed and tested local initiatives to increase responses and diversity, address disparities, and discover better practices.

We assessed the impact of metagenomic next-generation sequencing (mNGS) on patient care using previously established criteria. Among 37 patients receiving mNGS testing, 16% showed results that had a positive clinical impact. While mNGS results may offer valuable supplementary information, results should be interpreted within the broader clinical context and evaluation.

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.

Greater maternal depressive symptoms are consistently associated with higher levels of behavioral difficulties in children, emerging in early childhood and with long-lasting consequences for children’s development. Interventions promoting early relational health have been shown to have benefits for children’s behavior; however, these impacts are not always realized in the context of maternal depression. This study examined whether tiered programs could address this limitation by focusing on both parenting, through universal primary prevention, and psychosocial stressors and parent mental health, through tailored secondary prevention. Analysis of a randomized controlled trial (RCT) of the Smart Beginnings (SB) intervention was conducted to determine whether SB attenuated the association between maternal depression and early childhood internalizing and externalizing behaviors. Maternal depression significantly predicted both internalizing and externalizing behaviors in linear regression models. Further, there was a significant interaction between maternal depression and treatment group, such that among mothers with higher depressive symptoms, the SB treatment attenuated the magnitude of the association between depression and child behavior. Findings suggest that while parenting support is important for all families, it may be particularly critical for those with higher levels of depression and underscores the need to consider multidimensional family processes in both research and clinical practice.

In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.

Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

OBJECTIVES/GOALS: Empowering the Participant Voice (EPV) is a Rockefeller-led 6-CTSA consortium that aims to collect research participant feedback through new Research Participant Perception Survey (RPPS)/REDCap infrastructure and data aggregation to a national database. Here we describe diverse Use Cases and launch dissemination to other hubs. METHODS/STUDY POPULATION: The EPV team refined the RPPS-S and developed fielding and data standards, a multi-lingual RPPS/REDCap project XML, At-a-Glance Dashboard, EPV Consortium Database, and Use Cases to align with local initiatives and stakeholder input. Sites ran full thread tests of the infrastructure before launch. To demonstrate RPPS/REDCap, 5 sites implemented Use Cases, surveyed diverse populations via email, patient portal or SMS, and analyzed results using the At-a-Glance Dashboard External module (which provides visual analytics and enables filtering by participant/study characteristics). Sites continue to collect, synthesize and respond to actionable data. To disseminate infrastructure, we will invite early adopters to implement the RPPS/REDCap infrastructure locally, joining the EPV learning collective. RESULTS/ANTICIPATED RESULTS: To date, 5 sites surveyed 10,199 research participants, at post-consent or end of study. 2833 (26%) research participants responded, from diverse demographic groups. More than 90% gave the Top Box score response regarding courtesy, respect for cultural background, privacy, and lack of pressure to join a study. Disparities were apparent in the informed consent experience, with a Top Box score range of 38-78% in different demographics. Dissatisfaction with out-of-pocket research costs was a recurring theme. Top Box scores varied for feeling like a valued partner in research (69-93%), would recommend research participation to friends or family (56%-81%), and Overall Experience (64%-90%) questions. Sites identified actionable findings in areas of consent, communication, partnership, and study conduct. DISCUSSION/SIGNIFICANCE: The EPV RPPS/REDCap infrastructure enabled sites to broadly collect participant feedback, identify actionable findings and make inter-institutional comparisons. Collaborators are designing local initiatives to increase response rate and diversity, address disparities in research participation experiences, and discover better practices.

We describe the association between job roles and coronavirus disease 2019 (COVID-19) among healthcare personnel. A wide range of hazard ratios were observed across job roles. Medical assistants had higher hazard ratios than nurses, while attending physicians, food service workers, laboratory technicians, pharmacists, residents and fellows, and temporary workers had lower hazard ratios.

We describe COVID-19 cases among nonphysician healthcare personnel (HCP) by work location. The proportion of HCP with coronavirus disease 2019 (COVID-19) was highest in the emergency department and lowest among those working remotely. COVID-19 and non–COVID-19 units had similar proportions of HCP with COVID-19 (13%). Cases decreased across all work locations following COVID-19 vaccination.

Background: Whether working on COVID-19 designated units put healthcare workers (HCWs) at higher risk of acquiring COVID-19 is not fully understood. We report trends of COVID-19 incidence among nonphysician HCWs and the association between the risk of acquiring COVID-19 and work location in the hospital. Methods: The University of Iowa Hospitals & Clinics (UIHC) is an 811-bed, academic medical center serving as a referral center for Iowa. We retrospectively collected COVID-19–associated data for nonphysician HCWs from Employee Health Clinic between June 1st 2020 and July 31th 2021. The data we abstracted included age, sex, job title, working location, history of COVID-19, and date of positive COVID-19 test if they had a history of COVID-19. We excluded HCWs who did not have a designated working location and those who worked on multiple units during the same shift (eg, medicine resident, hospitalist, etc) to assess the association between COVID-19 infections and working location. Job titles were divided into the following 5 categories: (1) nurse, (2) medical assistant (MA), (3) technician, (4) clerk, and (5) others (eg patient access, billing office, etc). Working locations were divided into the following 6 categories: (1) emergency department (ED), (2) COVID-19 unit, (3) non–COVID-19 unit, (4) Clinic, (5) perioperative units, and (6) remote work. Results: We identified 6,971 HCWs with work locations recorded. During the study period, 758 HCWs (10.8%) reported being diagnosed with COVID-19. Of these 758 COVID-19 cases, 658 (86.8%) were diagnosed before vaccines became available. The location with the highest COVID-19 incidence was the ED (17%), followed by both COVID-19 and non–COVID-19 units (12.7%), clinics (11.0%), perioperative units (9.4%) and remote work stations (6.6%, p Conclusions: Strict and special infection control strategies may be needed for HCWs in the ED, especially where vaccine uptake is low. The administrative control of HCWs working remotely may be associated with a lower incidence of COVID-19. Given that the difference in COVID-19 incidence among HCWs by location was lower and comparable after the availability of COVID-19 vaccines, facilities should make COVID-19 vaccination mandatory as a condition of employment for all HCWs, especially in areas where the COVID-19 incidence is high.

Funding: None

Disclosures: None

Background: The IDSA has a clinical definition for catheter-related bloodstream infection (CRBSI) that requires ≥1 set of blood cultures from the catheter and ≥1 set from a peripheral vein. However, because blood cultures obtained from a central line may represent contamination rather than true infection, many institutions discourage blood cultures from central lines. We describe blood culture ordering practices in patients with a central line. Methods: The University of Iowa Hospitals & Clinics is an academic medical center with 860 hospital beds. We retrospectively collected data for blood cultures obtained from adult patients (aged ≥18 years) in the emergency department or an inpatient unit during 2020. We focused on the first blood cultures obtained during each admission because they are usually obtained before antibiotic initiation and are the most important opportunity to diagnose bacteremia. We classified blood-culture orders as follows: CRBSI workup, non-CRBSI sepsis workup, or incomplete workup. We defined CRBSI workup as ≥1 blood culture from a central line and ≥1 peripheral blood culture (IDSA guidelines). We defined non-CRBSI sepsis workup as ≥2 peripheral blood cultures without cultures from a central line because providers might have suspected secondary bacteremia rather than CRBSI. We defined incomplete workup as any order that did not meet the CRBSI or non-CRBSI sepsis workup. This occurred when only 1 peripheral culture was obtained or when ≥1 central-line culture was obtained without peripheral cultures. Results: We included 1,150 patient admissions with 4,071 blood cultures. In total, 349 patient admissions with blood culture orders (30.4%) met CRBSI workup. 62.8% were deemed non-CRBSI sepsis workup, and 6.9% were deemed an incomplete workup. Stratified by location, ICUs had the highest percentage of orders with incomplete workups (8.8%), followed by wards (7.2%) and the emergency department (5.1%). In total, 204 patient admissions had ≥1 positive blood culture (17.7%). The most frequently isolated organisms were Staphylococcus epidermidis (n = 33, 16.2%), Staphylococcus aureus (n = 16, 7.8%), and Escherichia coli (n = 15, 7.4%) Conclusions: Analysis of blood culture data allowed us to identify units at our institute that were underperforming in terms of ordering the necessary blood cultures to diagnose CRBSI. Being familiar with CRBSI guidelines as well as decreasing inappropriate ordering will help lead to early and proper diagnosis of CRBSI which can reduce its morbidity, mortality, and cost.

Funding: None

Disclosures: None

OBJECTIVES/GOALS: Six CTSA sites formed a collaboration to DEVELOP, DEMONSTRATE, AND DISSEMINATE new infrastructure to streamline collection and analysis of research participant feedback, using the Research Participant Perception Survey (RPPS), common standards, and customized REDCap-based tools, to improve the clinical research enterprise. METHODS/STUDY POPULATION: DEVELOP charter, consensus approach, core survey, deployment standards, data-use agreements; define meta-data, system requirements for the infrastructure, use-cases. Engage stakeholders for broad institutional and community input. Build RPPS/REDCap project, visual analytics Dashboard External Module, and Program Dashboard module for evaluation. Configure to use with Multilingual Module. DEMONSTRATE by implementing site-based use cases that reflect local priorities and span diverse populations, testing different methods of survey deployment (REDCap, patient portal, SMS) to showcase utility and flexibility. Generate data for local and inter-institutional benchmarking. Refine, then DISSEMINATE new infrastructure across the Consortium and REDCap community for broader testing and uptake. RESULTS/ANTICIPATED RESULTS: The project team refined the RPPS survey for inclusivity and mode of informed consent; defined standards for survey timing, sampling, and study metadata; configured the data dictionary in English and Spanishfor use with the multi-lingual module ; developed tools for project evaluation. Stakeholder engagement identified themes of anticipated value and fears about feedback. We designed an At-a-Glance Dashboard to display survey results with detailed analytics and filters. A REDCap application programming interface will send de-identified site data to the EPV Consortium Database to support benchmarking. Full implementation began November 2021 and will scale in 2022. Dissemination to Consortium and REDCap users is ongoing through presentations and a project website (www.Rockefeller.edu/research/epv). DISCUSSION/SIGNIFICANCE: Direct feedback from representative populations about their experiences in research is essential to understand and resolve barriers to broad participation in research. Streamlined RPPS/REDCap infrastructure provides a platform for local and national benchmarking, and collection of actionable data to improve clinical research.