ABSTRACT
BACKGROUND: A significant gap persists between evidence from research and its use in practice. Research funders, important actors in the health research system, can help reduce this gap by initiating dissemination and implementation (D&I) activities. The specific types of D&I activities funders currently lead have not been explored thoroughly. The Ensuring Value in Research (EViR) Funders' Forum-an international collaboration of health-related research funders-was established in 2017 to address research waste issues and increase the value of research. The Forum surveyed funders to learn about their D&I practices and challenges. METHODS: We distributed a five-item exploratory survey to participating funders in August 2018. The results informed the development of a survey instrument, distributed in June 2019. The survey instrument contained 15 items prompting respondents to categorize and describe their level of effort in six practice areas: release of findings, dissemination, knowledge exchange/partnering, implementation, building capacity, and implementation research. In addition, funders were asked to describe examples of their practices in detail. Thirty-one funders completed the survey instrument, a 58% response rate. RESULTS: Most funders regard D&I as a high priority, but funders vary in levels of activity per practice area. Over half of respondents reported that they have at least some activity in all D&I practice areas surveyed, with the exception of implementation research. The vast majority indicated some or significant activity in release of findings (97%) and dissemination (87%). Nearly one-fifth of funders (19%) indicated that implementation is outside their remit, and 26% indicated that implementation research is outside their remit. Survey respondents shared a broad range of examples of activities in each practice area. Lack of evidence for successful approaches and measuring impact were named frequently as challenges and as potential areas for collaboration. CONCLUSIONS: Although models of dissemination and implementation vary across organizations, the majority of funders indicated that D&I of research findings is a priority. Funders indicated a need for evidence on effectiveness of various approaches to D&I. Increased collaboration between funders, including sharing good practices, will increase our collective learning and knowledge development.
ABSTRACT
Importance: Incomplete information about existing research is an underlying cause of research waste. National and international initiatives and requirements have been launched to address this issue. Objectives: To characterize current clinical trial transparency policies among the largest noncommercial US funders and examine whether the policies are concordant with international funders. Design, Setting, and Participants: This retrospective review of public information used methods developed for documenting funder policies internationally; 2 researchers searched each funder's website and Google between May and November 2018 to locate trial transparency policies for 10 top US funders. Key informants at each funding organization were contacted by email and given 3 or more weeks to review and confirm or correct the findings. Nonresponders were contacted 2 or more additional times. Descriptive statistics were calculated to summarize the findings. The study was conducted using publicly available policy information with findings confirmed by funder representatives where possible. Participants included top 10 noncommercial US health research funders with the highest reported investment in health research (2013 dollars) who fund clinical trials. Data analysis was conducted from November 6, 2018, to November 23, 2018. Exposures: Availability of policies addressing each of the 3 key trial transparency domains as specified by the World Health Organization in 2017. Main Outcomes and Measures: Independent assessment by 2 investigators of availability (yes or no) of a policy addressing registration for trials, sharing of summary results, and individual participant data sharing activities; requirements (yes, no, or supportive statement) of these policies in terms of completeness, timeliness, public access, and provision of additional technical or financial support to meet data sharing requirements; description (yes or no) of internal monitoring for policy adherence. Results: All 10 funders acknowledged the outreach. One funder who indicated that less than 1% of their research funding goes to clinical trials was removed. Six (67%) of the remaining 9 top US funders have a publicly available written policy for all 3 major trial transparency domains. The most comprehensive trial transparency practice among US funders addresses summary results sharing as follows: 8 of 9 US funders (89%) have a policy, 5 of 9 US funders (56%) require reporting of summary results within 1 year, and 6 of 9 US funders (67%) monitor compliance with their summary results sharing policy. For clinical trial registration, 7 of 9 US funders (78%) have a policy and 5 of 9 US funders (56%) require registration and monitor trial registration to measure adherence to the policy. Conclusions and Relevance: In this study, overall the proportion of US funders with policies and practices to support trial transparency in this sample was similar or compared favorably with the larger international sample of noncommercial funders recently reported.
Subject(s)
Access to Information , Clinical Trials as Topic/organization & administration , Information Dissemination , Organizational Policy , Research Support as Topic/organization & administration , Biomedical Research/economics , Clinical Trials as Topic/economics , Humans , Retrospective Studies , United StatesABSTRACT
Axial spondyloarthritis (axSpA), which encompasses ankylosing spondylitis, is a complex genetic disease. Aberrant bone formation is a key feature of pathogenesis that can lead to ankylosis of the spine. Our objective is to determine, whether genes whose variants confer susceptibility to AS are expressed in bone progenitors like mesenchymal stem cells (MSCs). Since MSCs from bone marrow is difficult to obtain, we first examined, whether MSCs can be derived from induced pluripotent stem cells (iPSCs). Dermal fibroblasts of two axSpA patients and one healthy control were reprogrammed into iPSCs using a Sendai virus vector encoding pluripotency genes. Pluripotency of iPSCs was examined by embryoid body formation and by testing for stem cell specific gene and protein expression using RT-PCR and immuno fluorescence. iPSCs were differentiated into MSCs by a TGFß inhibitor. MSCs were characterized by flow cytometry using lineage specific antibodies and by their capacity to develop into chondrocytes, adipocytes, and osteoblasts in lineage-specific medium. RNA-seq was applied to determine genome-wide gene expression patterns in MSCs, iPSCs, and blood. We show for the first time, that expression levels of several AS susceptibility genes (EDIL3, ANO6, HAPLN1, ANTXR2) involved in bone formation are significantly elevated in MSCs (2-15-fold; p ≤ 0.05) compared to blood or iPSCs and demonstrate that iPSC-derived MSCs can be differentiated into osteoblasts, chondrocytes, and adipocytes. We conclude, MSCs generated from patient fibroblast-derived iPSC lines are useful tools for studying functional genomics of risk genes associated with bone formation in AS pathogenesis.
