This application seeks to conduct a large, pragmatic clinical trial demonstration project within the NIH Health Care Systems (HCS) Research Collaboratory. The Dialysis Research Network, comprised of academic investigators and dialysis provider organizations, is proposing the """"""""Time to Reduce Mortality in End-Stage Renal Disease (TiME)"""""""" trial. The TiME trial is a large, cluster-randomized, pragmatic trial that will evaluate the effects on survival, hospitalizations, and health-related quality of life of a systemaic implementation of a hemodialysis session duration of at least four hours for individuals with irreversible kidney failure who are initiating treatment with maintenance hemodialysis. The trial will be conducted in approximately 320 dialysis facilities owned by the two largest dialysis provider organizations in the United States. The electronic data systems of the dialysis provider organizations will be used for identification of participating dialysis facilities, for collection f trial data and outcomes, and for transmission of data to the University of Pennsylvania Clinical Research Computing Unit which will serve as the data coordinating center for the trial. The project will be implemented in two phases: the UH2 planning phase and the UH3 implementation phase, each of which has specific milestones for progress and metrics for evaluating the innovative approaches used for the trial. The Dialysis Research Network application fulfills the objectives of the NIH HCS Research Collaboratory Pragmatic Clinical Trials Demonstration Projects program. The TiME trial is pragmatic: 1) it evaluates an intervention implemented in the usual care setting, 2) it utilizes data that are obtained for routie clinical care, 3) it has minimal restrictions on eligibility, and 4) it requires no specific expertse of practitioners. The outcomes are important both clinically and from the perspective of the patient. The trial will be conducted through a partnership between academic investigators and two health care provider organizations with different business models, cultures, and electronic data systems. Innovative approaches that are relevant and applicable across a broad range of health care systems and diseases will be used for highly centralized execution of the trial, and tools wil be developed and shared with the broader research community. Thus, in addition to efficiently testing a simple but potentially high-impact intervention for patients with kidney failure, the TiM trial demonstration project will generate important advances for conducting cost-effective, large-scale clinical trials that assess the effectiveness of interventions in """"""""real-world"""""""" settings.

Public Health Relevance

The proposed pragmatic clinical trial will test a simple intervention to improve survival and quality of life for patients with kidney failure who require chronic treatment with dialysis. The trial will be conducted through a partnership between academic investigators and two large dialysis provider organizations. The pragmatic design of the trial, the utilization of multiple electronic health record systems for trial implementation, ad the partnership between academia and industry will establish a framework for conducting research within health care delivery systems that will be relevant and applicable to a broad range of diseases and research questions.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Exploratory/Developmental Cooperative Agreement Phase II (UH3)
Project #
Application #
Study Section
No Study Section (in-house review) (NSS)
Program Officer
Abbott, Kevin C
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Simon, Gregory E; Coronado, Gloria; DeBar, Lynn L et al. (2017) Data Sharing and Embedded Research. Ann Intern Med 167:668-670
Weinfurt, Kevin P; Hernandez, Adrian F; Coronado, Gloria D et al. (2017) Pragmatic clinical trials embedded in healthcare systems: generalizable lessons from the NIH Collaboratory. BMC Med Res Methodol 17:144
Courtright, Katherine R; Halpern, Scott D; Joffe, Steven et al. (2017) Willingness to participate in pragmatic dialysis trials: the importance of physician decisional autonomy and consent approach. Trials 18:474
Kraybill, Ashley; Dember, Laura M; Joffe, Steven et al. (2016) Patient and Physician Views about Protocolized Dialysis Treatment in Randomized Trials and Clinical Care. AJOB Empir Bioeth 7:106-115
Larson, Eric B; Tachibana, Chris; Thompson, Ella et al. (2016) Trials without tribulations: Minimizing the burden of pragmatic research on healthcare systems. Healthc (Amst) 4:138-41
Dember, Laura M; Archdeacon, Patrick; Krishnan, Mahesh et al. (2016) Pragmatic Trials in Maintenance Dialysis: Perspectives from the Kidney Health Initiative. J Am Soc Nephrol 27:2955-2963
Johnson, Karin E; Neta, Gila; Dember, Laura M et al. (2016) Use of PRECIS ratings in the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. Trials 17:32
Ellenberg, Susan S; Culbertson, Richard; Gillen, Daniel L et al. (2015) Data monitoring committees for pragmatic clinical trials. Clin Trials 12:530-6
Bonventre, Joseph V; Boulware, L Ebony; Dember, Laura M et al. (2014) The kidney research national dialogue: gearing up to move forward. Clin J Am Soc Nephrol 9:1806-11
Johnson, Karin E; Tachibana, Chris; Coronado, Gloria D et al. (2014) A guide to research partnerships for pragmatic clinical trials. BMJ 349:g6826