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.

Background:Previous studies have focused on 90-day outcomes in acute ischemic stroke patients who undergo thrombectomy, although long-term outcomes are not well understood. We compared the long-term rates of survival and new stroke recurrence among acute ischemic stroke patients who did and did not undergo thrombectomy. Methods:Using the Oracle Real-World Data (a de-identified large data source of multicenter electronic health records covering the period of January 2016 to January 2023), we analyzed 3,934 acute ischemic stroke patients who underwent thrombectomy and 3,934 propensity-matched controls of acute ischemic stroke patients who did not undergo thrombectomy. The risk of death or palliative care and new stroke following >90 days post-admission was ascertained using Cox proportional hazards regression analysis to adjust for potential confounders. We also estimated the rate of new stroke and palliative care-free survival using Kaplan-Meier survival analysis. Results:Among 3,934 acute ischemic stroke patients who underwent thrombectomy, 2,660 patients either died or received palliative care or developed new stroke (median follow-up period of 775 days post-initial stroke admission; interquartile range Q1 = 356 days, Q3 = 1,341 days). The 2-year new stroke and palliative care-free survival were 36.6 and 45.8% among patients who did and did not undergo thrombectomy, respectively (adjusted hazard ratio [HR], 1.19, 95% confidence interval [CI], 1.12-1.26). The risk of palliative care or death was not different (adjusted HR, 0.89, 95% CI, 0.77-1.02) between both groups, but the risk of new stroke was higher among patients who underwent thrombectomy (adjusted HR, 1.25, 95% CI, 1.18-1.33). Conclusion:Acute ischemic stroke patients who undergo thrombectomy are at greater risk of new stroke, palliative care, or death after 90 days, primarily driven by the occurrence of stroke. There is a need for closer surveillance and enhanced recurrent stroke prevention in this high-risk group.

Objectives:To develop and disseminate a technical framework for administering the Research Participant Perception Survey (RPPS) and aggregating data across institutions using REDCap. Materials and Methods:Six RPPS Steering Committee (RSC) member institutions met bi-weekly to achieve consensus on survey sampling techniques, data standards, participant and study descriptor variables, and dashboard design. Results:RSC members implemented the infrastructure to send the RPPS to participants and shared data to the Empowering the Participant Voice Consortium Database. Two pilot sites used the tools generated by the RSC to implement the RPPS. Discussion:The RSC created a REDCap project setup file, an external module visual analytics dashboard, an English/Spanish language file, and an implementation guide. Conclusion:The technical setup materials created by the RSC were effective in aiding new sites in implementing the RPPS and could help future sites adopt the RPPS to better understand participant experiences to improve research recruitment and retention.

INTRODUCTION:The extent and associated reasons or characteristics related to patients presenting to hospital prior with ST-elevation myocardial infarction (STEMI) are unknown. METHODS:This retrospective cohort study analyzed the Nationwide Readmission Database from 2018 to 2020 to evaluate hospitalizations within 30 days preceding a hospitalization with the diagnosis of STEMI in order to determine how often this occurs and what are the causes and factors associated with the recent admission. RESULTS:There were 1,355,765 hospital admissions with a diagnosis of STEMI and 54,545 (4.0 %) were hospitalized within 30-days prior to STEMI event. The most common causes of preceding hospitalization were sepsis, chronic ischemic heart disease, hypertensive disease with chronic kidney disease, complications of cardiac or vascular prosthetic devices, and implants/grafts, hypertensive heart disease with heart failure, and cerebral infarction. Independent factors associated with hospitalization within 30-days preceding STEMI, were cancer (OR 3.44 95 %CI 3.23-3.67, p < 0.001), elective admission (OR 2.76 95 %CI 2.59-2.95, p < 0.001), chronic kidney disease (OR 1.93 95 %CI 1.84-2.02, p < 0.001), chronic lung disease (OR 1.65 95 %CI 1.58-1.73, p < 0.001), previous stroke (OR 1.46 95 %CI 1.38-1.73, p < 0.001), and previous myocardial infarction (OR 1.45 95 %CI 1.37-1.53, p < 0.001). CONCLUSIONS:Among the 4.0 % of patients were admitted to hospital within 30-days prior to a later admission for STEMI, predictors of such admissions were sepsis, chronic ischemic heart disease and hypertension and cancer. This raises potential opportunities to prevent future admissions with STEMI once such patients are hospitalized.

Objective:The value of lipid lowering therapy (LLT) for prevention of atherosclerotic cardiovascular disease (ASCVD) is well understood. American College of Cardiology and American Heart Association guidelines recommend statin therapy for secondary and high-risk primary ASCVD prevention. Prior studies have identified incomplete uptake of these guidelines in specific practice settings or patient populations. Here we characterized real-world LLT prescribing relative to guideline recommendations across seven US health systems. Methods:Cross-sectional analyses of records from the PaTH Clinical Research Network focused on three cohorts: adults with ASCVD (ASCVD cohort), those aged 40-75 without ASCVD but with diabetes mellitus (DM cohort), and those not in either prior category but with a history of low-density lipoprotein (LDL-C) >190 mg/dl (LDL-C cohort). We describe patient characteristics, patterns of care, lipid values, and documented LLT within each cohort and variation between health systems. Results:We identified 240,625 patients within the ASCVD cohort (LDL-C mean 86, SD 40 mg/dL), 113,662 patients in the DM cohort (LDL-C mean 93, SD 37 mg/dL), and 11,276 patients in the LDL-C cohort (LDL-C mean 208, SD 33 mg/dL. Among ASCVD cohort members, 37 % achieved the target LDL-C < 70 mg/dL, 62 % were prescribed LLT, 34 % were prescribed guideline-concordant high-intensity statin therapy. In the DM cohort, 27 % had LDL-C < 70 mg/dl, 54 % were on statin therapy, 19 % on high-intensity statin therapy. In the LDL-C cohort, 97 % had an LDL-C > 160 mg/dl, 44 % were on statin therapy and 16 % on high-intensity statin therapy. There was significant variability in documented LLT between health systems. Conclusions:In this real-world descriptive study across multiple health systems for patients meeting criteria for secondary or high-risk primary ASCVD prevention, most patients had no documented high-intensity statin prescriptions and did not meet LDL-C targets. There was significant variability in care across health systems. Opportunities remain for improvement in guideline adherence to reduce ASCVD risk.

Background:Operational roadblocks and organizational delays in multicenter clinical trials have been evident for decades, with the start-up cycle being especially notorious for setbacks. To address these challenges and improve multicenter clinical trial execution, we developed an accelerated start-up (ASU) management strategy - a structured site onboarding approach based on lean management principles. Methods:Three elements were integrated into the strategy: a standardized workflow, a dedicated site navigator (SN), and an electronic tracking system. We examined the range, central tendencies, and distribution of site activation times among differing combinations of these three elements. To determine how these combinations affected individual start-up milestones, we fit mixed models to compare percent achievement of predetermined milestone benchmarks and time to completion. Results:Thirteen consecutive trials (n = 308 site activations) employed three distinct combinations of the three ASU elements. Trials using all three elements (n = 6) had 160 total site activations in a median of 133 days. Three trials without the SN element had 52 total site activations in a median of 191 days. Four trials without the standardized workflow element had 96 total site activations in a median of 277 days. Significant differences between combinations included times to sIRB submission (p = 0.004), training/certificates completion (p = 0.03), and site activation (p = 0.003). Results suggest sites activated faster and achieved predetermined benchmarks for every milestone more often when three elements were employed. Conclusion:This sample trial start-up data supports that sites can meet ambitious timelines, underscoring the strategy's potential to streamline workflows and improve site team performance.

BackgroundIndividuals who are socioeconomically disadvantaged have high smoking rates and face barriers to participating in smoking cessation interventions. Computer-tailored health communication, which is focused on finding the most relevant messages for an individual, has been shown to promote behavior change. We developed a machine learning approach (the Adapt2Quit recommender system), and our pilot work demonstrated the potential to increase message relevance and smoking cessation effectiveness among individuals who are socioeconomically disadvantaged. ObjectiveThis study protocol describes our randomized controlled trial to test whether the Adapt2Quit recommender system will increase smoking cessation among individuals from socioeconomically disadvantaged backgrounds who smoke. MethodsIndividuals from socioeconomically disadvantaged backgrounds who smoke were identified based on insurance tied to low income or from clinical settings (eg, community health centers) that provide care for low-income patients. They received text messages from the Adapt2Quit recommender system for 6 months. Participants received daily text messages for the first 30 days and every 14 days until the end of the study. Intervention participants also received biweekly texting facilitation messages, that is, text messages asking participants to respond (yes or no) if they were interested in being referred to the quitline. Interested participants were then actively referred to the quitline by study staff. Intervention participants also received biweekly text messages assessing their current smoking status. Control participants did not receive the recommender messages but received the biweekly texting facilitation and smoking status assessment messages. Our primary outcome is the 7-day point-prevalence smoking cessation at 6 months, verified by carbon monoxide testing. We will use an inverse probability weighting approach to test our primary outcome. This involves using a logistic regression model to predict nonmissingness, calculating the inverse probability of nonmissingness, and using it as a weight in a logistic regression model to compare cessation rates between the two groups. ResultsThe Adapt2Quit study was funded in April 2020 and is still ongoing. We have completed the recruitment of individuals (N=757 participants). The 6-month follow-up of all participants was completed in November 2024. The sample consists of 64% (486/757) female participants, 35% (265/757) Black or African American individuals, 51.1% (387/757) White individuals, and 16% (121/757) Hispanic or Latino individuals. In total, 52.6% (398/757) of participants reported having a high school education or being a high school graduate; 70% (529/757) smoked their first cigarette within 30 minutes of waking, and half (379/757, 50%) had stopped smoking for at least one day in the past year. Moreover, 16.6% (126/757) had called the quitline before study participation. ConclusionsWe have recruited a diverse sample of individuals who are socioeconomically disadvantaged and designed a rigorous protocol to evaluate the Adapt2Quit recommender system. Future papers will present our main analysis of the trial. Trial RegistrationClinicalTrials.gov NCT04720625; https://clinicaltrials.gov/study/NCT04720625 International Registered Report Identifier (IRRID)DERR1-10.2196/63693

Background The volume of mechanical thrombectomy (MT) performed at hospitals is used as one of the criteria for advanced-level designation for stroke care. Objective Our study sought to determine the relationship between annual MT procedural volume and in-hospital outcomes in acute ischemic stroke patients undergoing MT in the United States. Methods We analyzed the National Inpatient Sample from 2016 to 2020. The hospitals were grouped into quartiles based on the volume of MT procedures performed within the calendar year. We compared the rates of routine discharge/home health care; in-hospital mortality, and post-treatment intracranial hemorrhage (ICH) between the quartiles after adjusting for potential confounders. Results Patients undergoing MT ranged from 15,395 in quartile 1 to 78,510 MT in quartile 4. There were lower rates of discharge home/self-care of 22.5%, 20.8%, and 20.8% for quartiles 2, 3, and 4, respectively, compared with 34.9% in quartile 1. The odds of ICH increased to 1.81 (p < 0.001), 1.84 (p < 0.001), and 1.98 (p < 0.001) among the quartiles from lowest to highest procedural volumes. The odds of home discharge/self-care decreased to 0.66 (p < 0.001), 0.60 (p < 0.001), and 0.63 (p < 0.001) among the quartiles from lowest to highest procedural volumes. The odds of in-hospital mortality increased to 1.92 (p < 0.001), 1.99 (p < 0.001), and 1.84 (p < 0.001) among the quartiles from lowest to highest procedural volumes. Conclusions We observed a paradoxical relationship between adverse outcomes and the annual procedural volume of MT at the hospital presumably due to the higher severity of acute ischemic stroke treated at high-volume hospitals.

Background:Research participants" feedback about their participation experiences offers critical insights for improving programs. A shared Empowering the Participant Voice (EPV) infrastructure enabled a multiorganization collaborative to collect, analyze, and act on participants' feedback using validated participant-centered measures. Methods:A consortium of academic research organizations with Clinical and Translational Science Awards (CTSA) programs administered the Research Participant Perception Survey (RPPS) to active or recent research participants. Local response data also aggregated into a Consortium database, facilitating analysis of feedback overall and for subgroups. Results:From February 2022 to June 2024, participating organizations sent surveys to 28,096 participants and received 5045 responses (18%). Respondents were 60% female, 80% White, 13% Black, 2% Asian, and 6% Latino/x. Most respondents (85-95%) felt respected and listened to by study staff; 68% gave their overall experience the top rating. Only 60% felt fully prepared by the consent process. Consent, feeling valued, language assistance, age, study demands, and other factors were significantly associated with overall experience ratings. 63% of participants said that receiving a summary of the study results would be very important to joining a future study. Intersite scores differed significantly for some measures; initiatives piloted in response to local findings raised experience scores. Conclusion:RPPS results from 5045 participants from seven CTSAs provide a valuable evidence base for evaluating participants' research experiences and using participant feedback to improve research programs. Analyses revealed opportunities for improving research practices. Sites piloting local change initiatives based on RPPS findings demonstrated measurable positive impact.

This qualitative study describes the Trial Innovation Network's initial consultation process, which provides researchers with resources and recommendations to address complex aspects of planning and conducting clinical trials.

Placebo-controlled trials of sodium-glucose cotransporter-2 inhibitors (SGLT2i) demonstrate kidney and cardiovascular benefits for people with type 2 diabetes (T2D) and chronic kidney disease (CKD). We used real-world data to compare the kidney and cardiovascular effectiveness of empagliflozin to dipeptidyl peptidase-4 inhibitors (DPP4i), a commonly prescribed antiglycemic medication, in a diverse population with and without CKD. Using electronic health record data from 20 large US health systems, we leveraged propensity overlap weighting to compare outcomes for empagliflozin and DPP4i initiators with T2D between 2016 and 2020. The primary composite kidney outcome included 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease (ESKD), or all-cause mortality through 2 years or censoring. We also assessed cardiovascular and safety outcomes. Among 62,197 new users, 20,279 initiated empagliflozin, and 41,918 initiated DPP4i. Over a median follow-up of 1.1 years, empagliflozin prescription was associated with a lower risk of the primary outcome (HR 0.75, 95% CI 0.65-0.87) compared with DPP4i. Risks for mortality (HR 0.76, 95% CI 0.62-0.92) and a cardiovascular composite of stroke, myocardial infarction, or all-cause mortality (HR 0.81, 95% CI 0.70-0.95) were also lower for empagliflozin initiators. No difference in heart failure hospitalization risk between groups was observed. Genital mycotic infections were more common in patients prescribed empagliflozin (HR 1.72, 95% CI 1.58 - 1.88). Empagliflozin was associated with a lower risk of the primary outcome in patients with CKD (HR 0.68, 95% CI 0.53-0.88) and those without CKD (HR 0.79, 95% CI 0.67 - 0.94). In conclusion, initiation of empagliflozin was associated with a significantly lower risk of kidney and cardiovascular outcomes compared with DPP4i over a median of just over 1 year. The association with a lower risk for clinical outcomes was apparent even for people without known CKD at baseline.

Background Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed. Objectives The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D. Methods Using propensity score overlap weighting, we analyzed electronic health record data from 20 U.S. health systems contributing to PCORnet between 2015 and 2020. The primary kidney outcome was a composite of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease, or all-cause mortality over 2 years or until censoring. In addition, we examined cardiovascular and safety outcomes. Results The weighted study cohort included 35,004 SGLT2i and 47,268 GLP-1 RA initiators. Over a median of 1.2 years, the primary outcome did not differ between treatments (HR: 0.91; 95% CI: 0.81-1.02), although SGLT2i were associated with a lower risk of 40% eGFR decline (HR: 0.77; 95% CI: 0.65-0.91). Risks of mortality (HR: 1.08; 95% CI: 0.92-1.27), a composite of stroke, myocardial infarction, or death (HR: 1.03; 95% CI: 0.93-1.14), and heart failure hospitalization (HR: 0.95; 95% CI: 0.80-1.13) did not differ. Genital mycotic infections were more common for SGLT2i initiators, but other safety outcomes did not differ. The results were similar regardless of chronic kidney disease status. Conclusions SGLT2i and GLP-1 RAs led to similar kidney and cardiovascular outcomes in people with T2D, though SGLT2i initiation was associated with a lower risk of 40% eGFR decline. (Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease; NCT05465317)

BACKGROUND:In 2018, the time window for mechanical thrombectomy eligibility in patients with acute ischemic stroke increased from within 6 hours to within 24 hours of symptom onset. The purpose of this study was to evaluate the effect of window expansion on procedural and hospital volumes and patient outcomes at a national level. METHODS:We conducted a retrospective cohort study of patients with acute ischemic stroke undergoing mechanical thrombectomy using data from the National Inpatient Sample. We compared the numbers of mechanical thrombectomy procedures and performing hospitals between 2017 and 2019 in the USA, and the proportion of patients discharged home/self-care, those with in-hospital mortality and post-procedural intracranial hemorrhage (2019 vs 2017) after adjustment for potential confounders. RESULTS:The number of patients with ischemic stroke who underwent mechanical thrombectomy increased from 16 960 in 2017 to 28 120 in 2019. There was an increase in the number of hospitals performing mechanical thrombectomy (501 in 2017, 585 in 2019) and those performing ≥50 procedures/year (97 in 2017, 199 in 2019; P<0.001). The odds of in-hospital mortality decreased (OR 0.79, 95% CI 0.66 to 0.94, P=0.008) and the odds of intracranial hemorrhage increased (OR 1.18, 95% CI 1.06 to 1.31, P=0.003) in 2019 compared with 2017, with no change in odds of discharge to home. CONCLUSIONS:The window expansion for mechanical thrombectomy for patients with acute ischemic stroke was associated with an increase in the numbers of mechanical thrombectomy procedures and performing hospitals with a reduction of in-hospital mortality in the USA.

Background: There is conflicting evidence as to whether intra-arterial thrombolysis (IAT) adds benefit in patients with acute stroke who undergo mechanical thrombectomy (MT). Methods: We conducted a systematic review to identify studies that evaluate IAT in patients with acute stroke who undergo MT. Data were extracted from relevant studies found through a search of PubMed, Scopus, and Web of Science until February 2023. Statistical pooling with random effects meta-analysis was undertaken to evaluate odds of functional independence, mortality, and near-complete or complete angiographic recanalization with IAT compared to no IAT. Results: A total of 18 studies were included (3 matched, 14 unmatched, and 1 randomized). The odds ratio (OR) for functional independence (modified Rankin Scale: 0–2) at 90 days was 1.14 (95% confidence interval (CI): 0.95–1.37, p = 0.17, 16 studies involving 7572 patients) with IAT with moderate between-study heterogeneity (I 2 = 38.1%). The OR for functional independence with IAT was 1.28 (95% CI: 0.92–1.78, p = 0.15) in studies that were either matched or randomized and 1.24 (95% CI: 0.97–1.58, p = 0.08) in studies with the highest quality score. IAT was associated with higher odds of near-complete or complete angiographic recanalization (OR: 1.65, 95% CI: 1.03–2.65, p = 0.04) in studies that were either matched or of randomized comparisons. Conclusion: Although the odds of functional independence appeared to be higher with IAT and MT compared with MT alone, none of the results were statistically significant. A prominent effect of the design and quality of the studies was observed on the association between IAT and functional independence at 90 days.

BACKGROUND AND PURPOSE:Intraarterial thrombolysis as an adjunct to mechanical thrombectomy is increasingly being considered to enhance reperfusion in acute ischemic stroke patients. Intraarterial thrombolysis may increase the risk of post-thrombectomy intracerebral hemorrhage (ICH) in certain patient subgroups. METHODS:We analyzed acute ischemic stroke patients treated with mechanical thrombectomy in a multicenter registry. The occurrence of any (asymptomatic and symptomatic) post-thrombectomy ICH was ascertained using standard definition requiring serial neurological examinations and computed tomographic scans acquired within 48 hours of the thrombectomy. We determined the risk of ICH in subgroups defined by clinical characteristics and the use of intravenous (IV) thrombolysis. RESULTS:A total of 146 (7.5%) patients received intraarterial thrombolysis among 1953 acute ischemic stroke patients who underwent mechanical thrombectomy. The proportion of patients who developed any ICH was 26 (17.8%) and 510 (28.2%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .006). The proportion of patients who developed symptomatic ICH was 4 (2.7%) and 30 (1.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .34). Among patients who received IV thrombolysis (n = 1042), the proportion of patients who developed any ICH was 9 (16.7%) and 294 (30.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .028). The risk was not different in strata defined by age, gender, location of occlusion, preprocedure National Institutes of Health Stroke Scale score, time interval between symptom onset and thrombectomy, Alberta Stroke Program Early CT Score, systolic blood pressure, and serum glucose concentrations. CONCLUSIONS:In patients undergoing mechanical thrombectomy, the risk of any ICH and symptomatic ICH was not increased with intraarterial thrombolysis, including in those who had already received IV thrombolytics.

OBJECTIVES:The value of thrombectomy in patients with acute ischemic stroke cannot be understated. As such, whether these patients get access to this treatment can significantly impact their disease outcomes. We analyzed the trends in thrombectomy adoption between teaching and non-teaching hospitals in the United States, and their impact on overall patient care. MATERIALS AND METHODS:We conducted a retrospective analysis of hospital admissions in the Nationwide Inpatient Sample with a diagnosis of acute ischemic stroke between 2012 and 2020. We compared the annual total number and proportion of patients undergoing thrombectomy between teaching and non-teaching hospitals, and their corresponding outcomes. RESULTS:A total of 3,823,490 and 1,875,705 patients were admitted to teaching and non-teaching hospitals during the study duration, respectively. The proportion of patients who underwent thrombectomy increased from 1.60 % to 7.02 % (p-value for trend p < 0.001) in teaching hospitals and from 0.32 % to 2.20 % (p-value trend p < 0.001) in non-teaching hospitals. The absolute increase in the number of acute ischemic stroke patients undergoing thrombectomy was highest in teaching hospitals particularly those with large bed size, an increase from 3635 patients in 2012 to 24,730 patients in 2020. Higher rates of intravenous thrombolysis and patient transfer prior to thrombectomy were seen in teaching hospitals compared with non-teaching hospitals. CONCLUSIONS:The study highlights disparities between teaching and non-teaching hospitals, with teaching hospitals showing a disproportionately higher rate of thrombectomy adoption in acute ischemic stroke patients. Further studies are needed to understand the barriers to the adoption of thrombectomy in non-teaching hospitals.

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.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

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.