A majority of transplanted organs come from donors after brain death (BD). Renal grafts from these donors have higher delayed graft function and lower long-term survival rates compared to living donors. We designed a novel porcine BD model to better delineate the incompletely understood inflammatory response to BD, hypothesizing that adhesion molecule pathways would be upregulated in BD.

Animals were anesthetized and instrumented with monitors and a balloon catheter, then randomized to control and BD groups. BD was induced by inflating the balloon catheter and animals were maintained for 6 hours. RNA was extracted from kidneys, and gene expression pattern was determined.

In total, 902 gene pairs were differently expressed between groups. Eleven selected pathways were upregulated after BD, including cell adhesion molecules.

These results should be confirmed in human organ donors. Treatment strategies should target involved pathways and lessen the negative effects of BD on transplantable organs.

Real-world data, such as administrative claims and electronic health records, are increasingly used for safety monitoring and to help guide regulatory decision-making. In these settings, it is important to document analytic decisions transparently and objectively to assess and ensure that analyses meet their intended goals.

The Causal Roadmap is an established framework that can guide and document analytic decisions through each step of the analytic pipeline, which will help investigators generate high-quality real-world evidence.

In this paper, we illustrate the utility of the Causal Roadmap using two case studies previously led by workgroups sponsored by the Sentinel Initiative – a program for actively monitoring the safety of regulated medical products. Each case example focuses on different aspects of the analytic pipeline for drug safety monitoring. The first case study shows how the Causal Roadmap encourages transparency, reproducibility, and objective decision-making for causal analyses. The second case study highlights how this framework can guide analytic decisions beyond inference on causal parameters, improving outcome ascertainment in clinical phenotyping.

These examples provide a structured framework for implementing the Causal Roadmap in safety surveillance and guide transparent, reproducible, and objective analysis.

Although the involvement of citizen scientists in research can contribute to scientific benefits, much remains unknown about participants’ lived experiences in research. Thus, the purpose of this study was to explore how citizen scientists describe their role in, motivation for, and communication with researchers.

In-depth interviews (N = 9) were conducted with citizen scientists at a translational health research center.

Key results include that citizen scientists were invested in learning researchers’ discipline-specific language and viewed small group sizes as conducive to their active participation.

Programs can apply these findings in an effort to improve citizen scientists’ long-term engagement in research.

To conduct high-quality, rigorous research, and advance scientific knowledge, Translational Teams (TTs) engage in information behaviors, including seeking, using, creating, sharing, storing, and retrieving information, in ways specific to the translational context. Currently, little is known about TTs’ approach to information management. This qualitative pilot study explored how TTs at the University of Wisconsin-Madison interact with information, as well as the scientific and organizational impact of their interactions.

We conducted interviews with ten members of UW TTs. Interviews were transcribed and thematic analysis was conducted.

Four themes emerged: (1) TT members did not recognize the centrality of information or information behaviors to their scientific work; (2) TT members engaged in similar information behaviors and used similar tools across disciplines and topics; (3) TT members did not receive support or guidance from their institution in managing information; and (4) Individualized choices of TT members conflicted at the team level, causing confusion and increasing the potential for data and information loss. Acting as freelance information management agents, TT members made individualized decisions about what tools to use and how to use them, often in a piecemeal manner and without communicating these decisions to other team members.

Research institutions should both encourage teams to discuss their information management approaches at the beginning of a project and provide leaders with training on how to have these conversations and what topics should be included. Additionally, institutions can provide researchers with guidelines for using software platforms to help mitigate information management challenges.

Clinical and Translational Research (CTR) requires a team-based approach, with successful teams engaging in skilled management and use of information. Yet we know little about the ways that Translational Teams (TTs) engage with information across the lifecycle of CTR projects. This qualitative study explored the challenges that information management imposes on the conduct of team-based CTR.

We conducted interviews with ten members of TTs at University of Wisconsin. Interviews were transcribed and thematic analysis was conducted.

TTs’ piecemeal and reactive approaches to information management created conflict within the team and slowed scientific progress. The lack of cohesive information management strategies made it more difficult for teams to develop strong team processes like communication, scientific coordination, and project management. While TTs’ research was hindered by the institutional challenges of interdisciplinary team information sharing, TTs who had developed shared approaches to information management that foregrounded transparency, accountability, and trust, described substantial benefits to their teamwork.

We propose a new model for the Science of Team Science field – a Translational Team Science Hierarchy of Needs – that suggests interventions should be targeted at the appropriate stage of team development in order to maximize a team’s scientific potential.

Academic health systems and their investigators are challenged to systematically assure clinical research regulatory compliance. This challenge is heightened in the emerging era of centralized single Institutional Review Boards for multicenter studies, which rely on monitoring programs at each participating site.

To describe the development, implementation, and outcome measurement of an institution-wide paired training curriculum and internal monitoring program for clinical research regulatory compliance.

Standard operating procedures (SOPs) were developed to facilitate investigator and research professional adherence to institutional policies, federal guidelines, and international standards. An SOP training curriculum was developed and implemented institution-wide. An internal monitoring program was launched, utilizing risk-based monitoring plans of pre-specified frequency and intensity, assessed upon Institutional Review Boards approval of each prospective study. Monitoring plans were executed according to an additional SOP on internal monitoring, with monitoring findings captured in a REDCap database.

We observed few major violations across 3 key domains of clinical research conduct and demonstrated a meaningful decrease in the rates of nonmajor violations in each, over the course of 2 years.

The paired training curriculum and monitoring program is a successful institution-wide clinical research regulatory compliance model that will continue to be refined.

Incorporating real-world data using “big data” analysis in healthcare are useful to extract specific information for healthcare delivery system improvement. All-cause mortality is an essential measure to enhance patient safety in clinical trial research, especially for underrepresented pediatric participants.

This study aimed to determine the associations between pediatric mortality and patient-specific factors using the Healthcare Cost and Utilization Project (HCUP) database.

Data from the 2019 the HCUP Kids’ Inpatient Database (KID) were used to conduct a logistic regression analysis to determine associations between pediatric patients’ the chance of survival and their demographic and socioeconomic background, discharge records, and hospital information.

Total number of diagnoses (OR = 0.84), total number of procedures (OR = 0.86), length of stay (OR = 1.04), age intervals greater than 1 year (OR > 1.0), transfer into the hospital from a different acute care (OR = 0.34), major diagnoses of multiple significant trauma (OR = 0.03) or hepatobiliary system and pancreas (OR = 0.10), region of hospital – west and midwest (OR > 1.0), and medium or larger hospital bed size (OR > 1.0) were all significantly associated with the chance of survival for patients participating in pediatric clinical trials (p < 0.05).

Real-world clinical trial data analysis showed the potential improvement area including reallocating trial resources to promote trial quality and safe participation for pediatric patients. Pediatric trials need tools that are developed using user-centered design approaches to satisfy the unique needs and requirements of pediatric patients and their caregivers. Safe intrahospital transfer procedures and active dissemination of successful trial best practices are crucial to trial management, adherence, quality, and safety.

The Fibrosis-4 (FIB-4) index, a simple index that includes age, liver enzymes, and platelet count has been studied as a tool to identify patients at a risk of requiring mechanical ventilation due to its high negative predictive value. It is unknown if FIB-4 remains useful to predict the severity of respiratory disease requiring mechanical ventilation amongst new Coronavirus disease 2019 (COVID-19) variants and whether a relationship also exists between FIB-4 and 30-day mortality. The main objective was to determine if FIB-4 can predict mechanical ventilation requirements and 30-day mortality from COVID-19 across variants including Alpha, Delta, and Omicron.

This was a population-based, retrospective cohort analysis of 232,364 hospitalized patients in the National COVID-19 Cohort Collaborative between the age of 18–90 who tested positive for COVID-19 between April 27, 2020 and June 25, 2022. The primary outcome was association between FIB-4 and need for mechanical ventilation. Secondary measures included the association of FIB-4 with 30-day mortality.

A FIB-4 > 2.67 had 1.8 times higher odds of requiring mechanical ventilation across all variants of COVID-19 (OR 1.81; 95% CI: [1.76, 1.86]). The area under the ROC curve showed high diagnostic accuracy with values ranging between 0.79 (Omicron wave) and 0.97 (delta wave). Increased FIB-4 was associated with 30-day mortality across the variates.

The FIB-4 was consistently associated with both increased utilization of mechanical ventilation and 30-day mortality among COVID-19 patients across all waves in both adjusted and unadjusted models. This provides a simple tool for risk-stratification for front-line health care professionals.

A lack of standardized clinical research coordinator (CRC) training programs requires determining appropriate approaches for content delivery. The purpose of this study was to assess CRCs preferred training delivery methods related to the 8 designated Joint Task Force Clinical Trial Competency domains.

Repeated measures analysis of variance and split-plot analysis of variance were adopted to compare the group means among 5 training delivery methods by 8 competency content domains and to examine whether demographic variables caused different preference patterns on the training delivery methods.

Participants reported a preference for online video; mentoring/coaching was the least preferred. Significant training delivery method preferences were reported for 3 content domains: participant safety considerations, medicines development and regulation, and clinical trials operations.

Observed statistical differences in the training delivery methods by the content domains provides guidance for program development. Ensuring that standardized educational training is aligned with the needs of adult learners may help ensure that CRCs are appropriately prepared for the workforce.

A core challenge of a multidisciplinary and multi-organizational translational research enterprise such as a Clinical and Translational Research Award (CTSA) is coordinating and integrating the work of individuals, workgroups, and organizations accustomed to working independently and autonomously. Tufts Clinical and Translational Science Institute (CTSI) undertook and studied a multifacted intervention to address this challenge and to create a culture of systems thinking, process awareness, responsive to others' needs, and shared decision-making.

The intervention, based on relational coordination, included 1) relational interventions, in three staff retreats and a diagnostic survey to provide feedback on the current quality of relational coordination, and 2) structural interventions, in the launching of five new cross-functional teams with regular meeting structures.

A mixed-methods evaluation yielded quantitative data via two types of team surveys and qualitative data via interviews and meeting observations.

The findings suggest that interventions to improve relational coordination are feasible for CTSAs, including good fidelity to the model and staff/physician engagement. Survey and interview data suggest model improvements in coordination and alignment. Further research about their optimal design is warranted.