The Prevalence of Dissemination and Implementation Research and Training Grants at National Cancer Institute-Designated Cancer Centers.

Background: Dissemination and implementation (D&I) research is a key factor in the uptake and use of evidence-based cancer control interventions. National Cancer Institute (NCI)-designated cancer centers are ideal settings in which to further D&I knowledge. The purpose of this study was to summarize the characteristics of NCI-funded D&I science grants in the nation's cancer centers to understand the nature, extent, and opportunity for this key type of translational work. Methods: We used the National Institutes of Health Research Portfolio Online Reporting Tool to identify active NCI-funded grants in D&I science at NCI clinical cancer centers (n = 13) and comprehensive cancer centers (n = 51) as well as their academic affiliates. Active projects were eligible for inclusion if they 1) were awarded directly to an NCI cancer center or an academic or research affiliate, and 2) identified D&I content in the abstract. Portfolio data were collected in February 2021. Results: We identified 104 active NCI-funded D&I research or training grants across the 64 cancer centers; 57.8% of cancer centers had at least 1 NCI-funded D&I grant. Most awards (71.1%) were for research grants. Training grants constituted 29.1% of D&I-focused grants. Overall, 50.0% of grants (n = 52) concentrated on specific cancers. Almost two-thirds of grants (n = 68, 65.4%) had a stated health equity focus. Conclusions: More than one-half of NCI-designated cancer centers have active funding in D&I science, reflecting a substantial investment by NCI. There remains considerable room for further development, which would further support NCI's translational mission.

Plasma S1P (Sphingosine-1-Phosphate) Links to Hypertension and Biomarkers of Inflammation and Cardiovascular Disease: Findings From a Translational Investigation.

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Analysing the attributes of Comprehensive Cancer Centres and Cancer Centres across Europe to identify key hallmarks.

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals.

Reporting experimental studies on animals - The problems with translating of outcomes to clinical benefits. Methodological and statistical considerations: The example of pulmonary hypertension.

The variability inherent in animal models and the methods used to define drug response can lead to highly divergent results when evaluating new drug candidates. Several guidelines exist for high-quality and comprehensive reporting of experiments with animals. The present survey makes a quantitative demonstration of whether compliance with good preclinical practice guidelines can affect the results and reduce risk of over- or underestimation of treatment benefit. This meta-analysis was performed on more than 400 animal studies concerning pulmonary hypertension, where a wide range of potential therapeutic agents have been recently positively assessed in preclinical experiments. The experiments were reviewed according to the selected methodological and statistical items being recommended to report in papers. A quantitative evaluation was performed of their impact on effect size, which defined the efficacy of particular drug candidates. In addition, the paper also examines whether the quality score calculated for the papers included in the analysis changed over the previous 25 years. In conclusion, some information in experimental studies is often missed or incomplete, which complicates the correct evaluation and comprehension of obtained results. This in turn could subsequently increase the potential hazards involved in translating positive experimental outcomes to possible clinical benefits in patients.

Approaches for the integration of big data in translational medicine: single-cell and computational methods.

Translational medicine describes a bench-to-bedside approach that eventually converts findings from basic scientific studies into real-world clinical research. It encompasses new treatments, advanced equipment, medical procedures, preventive and diagnostic approaches creating a bridge between basic studies and clinical research. Despite considerable investment in basic science, improvements in technology, and increased knowledge of the biology of human disease, translation of laboratory findings into substantial therapeutic progress has been slower than expected, and the return on investment has been limited in terms of clinical efficacy. In this review, we provide a fresh perspective on some experimental and computational approaches for translational medicine. We cover the analysis, visualization, and modeling of high-dimensional data, with a focus on single-cell technologies, sequence, and structure analysis. Current challenges, limitations, and future directions, with examples from cancer and fibrotic disease, will be discussed.

Environmental Scan on Canadian Interactive Knowledge Translation Tools to Prevent Diabetes Complications in Patients With Diabetes.

In this study, we identify existing interactive knowledge translation tools that could help patients and health-care professionals to prevent diabetes complications in the Canadian context. We conducted an environmental scan in collaboration with researchers and 4 patient partners across Canada. We conducted searches among the research team members, their networks and Twitter, and through searches in databases and Google. To be included, interactive knowledge translation tools had to meet the following criteria: used to prevent diabetes complications; used in a real-life setting; used any instructional method or material; had relevance in the Canadian context, written in English or French; developed and/or published by experts in diabetes complications or by a recognized organization; created in 2013 or after; and accessibility online or on paper. Two reviewers independently screened each record for selection and extracted the following data: authorship, objective(s), patients' characteristics, type of diabetes complications targeted, type of knowledge users targeted and tool characteristics. We used simple descriptive statistics to summarize our results. Thirty-one of the 1,700 potentially eligible interactive knowledge translation tools were included in the scan. Tool formats included personal notebook, interactive case study, risk assessment tool, clinical pathway, decision support tool, knowledge quiz and checklist. Diabetes complications targeted by the tools included foot-related neuropathy, cardiovascular diseases, mental disorders and distress and any complications related to diabetes and kidney disease. Our results inform Canadian stakeholders interested in the prevention of diabetes complications to avoid unnecessary duplication, identify gaps in knowledge and support implementation of these tools in clinical and patients' decision-making.

Performance Index for Types of Clinical Research Support Service Providers for Academic Research Organizations in Japan: A Cross-Sectional Survey.

The purpose of this study was to conduct a factual survey to evaluate the type of clinical research support offered by service providers (supporters) in Japanese academic research organizations (AROs). From September to October 2018, we conducted an online questionnaire targeting researchers and supporters of AROs, including individuals supporting research and development (R&D) planning, as well as those involved in study management, biostatistics, coordination, data management, monitoring, and auditing. The number of responses was tabulated for each survey item. For items with written descriptions, we compiled summaries using the inductive regression method of qualitative research. Responses were obtained from 124 researchers, 258 supporters, and 40 AROs. None of the institutions responded that they had a performance index for all types of service providers, whereas 47% of institutions had an index for 1-3 types of service providers, and 40% of institutions had no index. Many institutions responded that they had a performance index for coordinators and data management, but few responded that there was a performance index for individuals engaged in R&D and study management. Furthermore, for all evaluations of AROs and researchers, the level of supporter satisfaction was low at only 20%. There was a discrepancy between the levels of researcher expectations and the actual contribution of R&D in the process of research planning. Our survey revealed that there is currently no performance index for services supporting clinical research. In future studies, we need to examine a performance index that accurately reflects the researcher attitudes revealed in this study.

Recognizing Cross-Institutional Fiscal and Administrative Barriers and Facilitators to Conducting Community-Engaged Clinical and Translational Research.

PURPOSE: This qualitative study examined fiscal and administrative (i.e., pre- and post-award grants process) barriers and facilitators to community-engaged research among stakeholders across 4 Clinical and Translational Science Awards (CTSA) institutions. METHOD: A purposive sample of 24 key informants from 3 stakeholder groups-community partners, academic researchers, and research administrators-from the CTSA institutions at the University of North Carolina at Chapel Hill, Medical University of South Carolina, Vanderbilt University Medical Center, and Yale University participated. Semistructured interviews were conducted in March-July 2018, including questions about perceived challenges and best practices in fiscal and administrative processes in community-engaged research. Transcribed interviews were independently reviewed and analyzed using the Rapid Assessment Process to facilitate key theme and quote identification. RESULTS: Community partners were predominantly Black, academic researchers and research administrators were predominantly White, and women made up two-thirds of the overall sample. Five key themes were identified: level of partnership equity, partnership collaboration and communication, institutional policies and procedures, level of familiarity with varying fiscal and administrative processes, and financial management expectations. No stakeholders reported best practices for the institutional policies and procedures theme. Cross-cutting challenges included communication gaps between stakeholder groups; lack of or limits in supporting community partners' fiscal capacity; and lack of collective awareness of each stakeholder group's processes, procedures, and needs. Cross-cutting best practices centered on shared decision making and early and timely communication between all stakeholder groups in both pre- and post-award processes. CONCLUSIONS: Findings highlight the importance of equitable processes, triangulated communication, transparency, and recognizing and respecting different financial management cultures within community-engaged research. This work can be a springboard used by CTSA institutions to build on available resources that facilitate co-learning and discussions between community partners, academic researchers, and research administrators on fiscal readiness and administrative processes for improved community-engaged research partnerships.

Building a System to Engage and Sustain Research Careers for Physicians.

There are increasing needs for physician-investigators to translate the rapid expansion of knowledge, technology/interventions, and big data into the clinical realm at a time of increasing age-related disabilities and communicable diseases. Yet, the number of physician-investigators has continued to decline, and only a small number of medical school graduates in the United States are actively engaged in research. This problem may be particularly pronounced in small- and medium-sized academic institutions due to more limited educational and mentoring infrastructure. Neither efforts by the federal government nor isolated institutional programs alone have been effective yet in solving this problem. This article describes an integrated institutional strategy undertaken at Penn State College of Medicine that is focused on developing and sustaining a physician-investigator workforce. Key elements of this strategy are new programs to close gaps in the professional life cycle of physician-investigators, dedicated senior leaders collaborating with an experienced and diverse advisory committee, and a data-driven approach to programmatic evaluation. In this article, the implementation of integrated institutional programs including Institutional Mock Review for evaluation of grant proposals before submission, physician-scientist faculty mentoring, and effort matching programs are described. Detailed tactics are offered for tailoring these programs to a particular institution's background to maximize both efficiency and sustainability. The overarching strategy includes engaging multidisciplinary faculty as mentors and mentees, partnering with both clinical and basic science departments, integrating new programs with established approaches, and cultivating an emerging generation of physician-investigators as near-peer mentors and future leaders. This approach may serve as a useful paradigm for building an environment to nurture junior physician-investigators at other mid-sized academic institutions and may also have value for larger institutions in which there is fragmentation of the efforts to sustain the research careers of physicians.

Markers of achievement for assessing and monitoring gender equity in a UK National Institute for Health Research Biomedical Research Centre: A two-factor model.

BACKGROUND: The underrepresentation of women in academic medicine at senior level and in leadership positions is well documented. Biomedical Research Centres (BRC), partnerships between leading National Health Service (NHS) organisations and universities, conduct world class translational research funded by the National Institute for Health Research (NIHR) in the UK. Since 2011 BRCs are required to demonstrate significant progress in gender equity (GE) to be eligible to apply for funding. However, the evidence base for monitoring GE specifically in BRC settings is underdeveloped. This is the first survey tool designed to rank and identify new GE markers specific to the NIHR BRCs. METHODS: An online survey distributed to senior leadership, clinical and non-clinical researchers, trainees, administrative and other professionals affiliated to the NIHR Oxford BRC (N = 683). Participants ranked 13 markers of GE on a five point Likert scale by importance. Data were summarised using frequencies and descriptive statistics. Interrelationships between markers and underlying latent dimensions (factors) were determined by exploratory and confirmatory factor analyses. RESULTS: The response rate was 36% (243 respondents). Respondents were more frequently female (55%, n = 133), aged 41-50 years (33%, n = 81), investigators (33%, n = 81) affiliated to the BRC for 2-7 years (39.5%, n = 96). Overall participants ranked 'BRC senior leadership roles' and 'organisational policies on gender equity', to be the most important markers of GE. 58% (n = 141) and 57% (n = 139) respectively. Female participants ranked 'organisational policies' (64.7%, n = 86/133) and 'recruitment and retention' (60.9%, n = 81/133) most highly, whereas male participants ranked 'leadership development' (52.1%, n = 50/96) and 'BRC senior leadership roles' (50%, n = 48/96) as most important. Factor analyses identified two distinct latent dimensions: "organisational markers" and "individual markers" of GE in BRCs. CONCLUSIONS: A two-factor model of markers of achievement for GE with "organisational" and "individual" dimensions was identified. Implementation and sustainability of gender equity requires commitment at senior leadership and organisational policy level.

The National Center for Advancing Translational Sciences' Intramural Training Program and Fellow Career Outcomes.

The National Center for Advancing Translational Sciences (NCATS) defines translational science as "the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process." A major goal of translational science is to determine commonalities across projects to identify principles for addressing persistent bottlenecks in this process. To meet this goal, translational scientists must be conversant in multiple disciplines, work in teams, and understand the larger translational science ecosystem. The development of these skills through translational science training opportunities, such as the translational science training offered by the NCATS intramural research program, prepares fellows for a variety of career options. The unique structure of the NCATS intramural program and the career outcomes of its alumni are described herein to demonstrate the distinct features of this training environment, the productivity of fellows during their time in training, and how this prepares fellows to be competitive for a variety of science careers. To date, the NCATS intramural research program has trained 213 people, ranging from high school to postdoctoral levels. These alumni have transitioned into a wide array of career functions, types, and sectors.

Generalized Additive Mixed Modeling of Longitudinal Tumor Growth Reduces Bias and Improves Decision Making in Translational Oncology.

Scientists working in translational oncology regularly conduct multigroup studies of mice with serially measured tumors. Longitudinal data collected can feature mid-study dropouts and complex nonlinear temporal response patterns. Parametric statistical models such as ones assuming exponential growth are useful for summarizing tumor volume over ranges for which the growth model holds, with the advantage that the model's parameter estimates can be used to summarize between-group differences in tumor volume growth with statistical measures of uncertainty. However, these same assumed growth models are too rigid to recapitulate patterns observed in many experiments, which in turn diminishes the effectiveness of their parameter estimates as summary statistics. To address this problem, we generalized such models by adopting a nonparametric approach in which group-level response trends for logarithmically scaled tumor volume are estimated as regression splines in a generalized additive mixed model. We also describe a novel summary statistic for group level splines over user-defined, experimentally relevant time ranges. This statistic reduces to the log-linear growth rate for data well described by exponential growth and also has a sampling distribution across groups that is well approximated by a multivariate Gaussian, thus facilitating downstream analysis. Real-data examples show that this nonparametric approach not only enhances fidelity in describing nonlinear growth scenarios but also improves statistical power to detect interregimen differences when compared with the simple exponential model so that it generalizes the linear mixed effects paradigm for analysis of log-linear growth to nonlinear scenarios in a useful way. SIGNIFICANCE: This work generalizes the statistical linear mixed modeling paradigm for summarizing longitudinally measured preclinical tumor volume studies to encompass studies with nonlinear and nonmonotonic group response patterns in a statistically rigorous manner.

What happened to the US cancer cooperative groups? A status update ten years after the Institute of Medicine report.

The US cancer cooperative groups (cooperative groups) were founded in the 1950s to establish a standing infrastructure to conduct multi-institutional cancer clinical trials. Initially funded almost entirely by the US National Cancer Institute (NCI), over the years, the research conducted by the Cooperative Groups has evolved to meet the demands of cancer clinical research, with a scope now encompassing trials to advance cancer treatment, cancer control, biomarker development and validation, and health services research, with a corresponding broadening of their funding sources. The cooperative groups are also a critical mechanism for educating the next generation of cancer clinical trialists from many different disciplines. This review outlines the overall mission, structure, and funding of the cooperative groups, beginning in 1955 when they were first established by the NCI, and describes the considerable progress against cancer achieved over the past decade.

Impact of a Formal Educational Skill-Building Program Based on the ARCC Model to Enhance Evidence-Based Practice Competency in Nurse Teams.

BACKGROUND: Implementation of evidence-based practice (EBP) is necessary for healthcare systems to improve quality, safety, patient outcomes, and costs. Yet, EBP competency is lacking in many nurses and clinicians across the country. AIM: The purpose of this initiative was to determine whether nursing teams (Executive Leader, Clinical/Mid-level Leader, and Direct Care Nurse) attending a 5-day EBP continuing education skill-building program (immersion) was an effective strategy to build EBP competence, practice, and culture sustainability over time. The Advancing Research and Clinical Practice Through Close Collaboration Model was used to guide this initiative. METHODS: A project team was assembled, including leaders with EBP expertise from the Air Force Medical Service and The Helene Fuld Health Trust National Institute for EBP in Nursing and Healthcare at The Ohio State University. Five survey instruments were used to evaluate outcomes, including Organizational Culture and Readiness for System-Wide Implementation of Evidence-Based Practice, Evidence-Based Practice Beliefs, Evidence-Based Practice Implementation, and Evidence-Based Practice Competencies, as well as the Knowledge Assessment Questionnaire test. Nursing teams were invited to participate and complete the program with the implementation of EBP projects over the following year. RESULTS: Participants' EBP knowledge, skills, competencies, and beliefs were significantly improved and sustained over 12 months. LINKING EVIDENCE TO ACTION: A team-based EBP skill-building program was an effective strategy for building EBP competence, practice, and culture. This initiative demonstrated that the direct involvement of leadership and infrastructure to support EBP were crucial factors for building and sustaining an EBP culture.

Realistic simulation of virtual multi-scale, multi-modal patient trajectories using Bayesian networks and sparse auto-encoders.

Translational research of many disease areas requires a longitudinal understanding of disease development and progression across all biologically relevant scales. Several corresponding studies are now available. However, to compile a comprehensive picture of a specific disease, multiple studies need to be analyzed and compared. A large number of clinical studies is nowadays conducted in the context of drug development in pharmaceutical research. However, legal and ethical constraints typically do not allow for sharing sensitive patient data. In consequence there exist data "silos", which slow down the overall scientific progress in translational research. In this paper, we suggest the idea of a virtual cohort (VC) to address this limitation. Our key idea is to describe a longitudinal patient cohort with the help of a generative statistical model, namely a modular Bayesian Network, in which individual modules are represented as sparse autoencoder networks. We show that with the help of such a model we can simulate subjects that are highly similar to real ones. Our approach allows for incorporating arbitrary multi-scale, multi-modal data without making specific distribution assumptions. Moreover, we demonstrate the possibility to simulate interventions (e.g. via a treatment) in the VC. Overall, our proposed approach opens the possibility to build sufficiently realistic VCs for multiple disease areas in the future.

Quality and validity of large animal experiments in stroke: A systematic review.

An important factor for successful translational stroke research is study quality. Low-quality studies are at risk of biased results and effect overestimation, as has been intensely discussed for small animal stroke research. However, little is known about the methodological rigor and quality in large animal stroke models, which are becoming more frequently used in the field. Based on research in two databases, this systematic review surveys and analyses the methodological quality in large animal stroke research. Quality analysis was based on the Stroke Therapy Academic Industry Roundtable and the Animals in Research: Reporting In Vivo Experiments guidelines. Our analysis revealed that large animal models are utilized with similar shortcomings as small animal models. Moreover, translational benefits of large animal models may be limited due to lacking implementation of important quality criteria such as randomization, allocation concealment, and blinded assessment of outcome. On the other hand, an increase of study quality over time and a positive correlation between study quality and journal impact factor were identified. Based on the obtained findings, we derive recommendations for optimal study planning, conducting, and data analysis/reporting when using large animal stroke models to fully benefit from the translational advantages offered by these models.

Transferability of a diabetes escape room into an accelerated pharmacy program.

BACKGROUND AND PURPOSE: Educational games can be used to increase students' knowledge of diabetes management. Students perceive educational games to be valuable learning tools. This study evaluated the transferability of a serious game, the diabetes escape room, between skills laboratories in a traditional program and an accelerated program. The authors believe that this is a valuable addition to educational methods for students in any pharmacy program. EDUCATIONAL ACTIVITY AND SETTING: Faculty at an accelerated, three-year pharmacy program replicated a diabetes escape room previously used by a traditional, four-year pharmacy program. The diabetes escape room required students to compete in a team-based educational game in which they solved diabetes-themed puzzles. Students completed pre- and post-game knowledge assessments and a perception survey linked to activity participation. The accelerated program students completed an additional delayed post-game knowledge assessment. FINDINGS: Students showed a statistically significant difference between pre- and post-game knowledge assessment scores at both institutions as well as in the delayed post-game knowledge assessment implemented at the accelerated program. Perception survey results were statistically significantly higher for the accelerated program, however both cohorts suggested positive perceived engagement with and usefulness of the escape room. SUMMARY: The use of a diabetes escape room resulted in statistically significant gains in knowledge and positive student perceptions. The diabetes escape room is a transferrable activity that can be used by other colleges or schools of pharmacy.