The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration.

Background: Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established.

Methods: To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate.

Considerations in the evaluation and determination of minimal risk in pragmatic clinical trials.

Institutional review boards, which are charged with overseeing research, must classify the riskiness of proposed research according to a federal regulation known as the Common Rule (45 CFR 46, Subpart A) and by regulations governing the US Food and Drug Administration codified in 21 CFR 50. If an institutional review board determines that a clinical trial constitutes "minimal risk," there are important practical implications: the institutional review board may then allow a waiver or alteration of the informed consent process; the study may be carried out in certain vulnerable populations; or the study may be reviewed by institutional review boards using an expedited process. However, it is unclear how institutional review boards should assess the risk levels of pragmatic clinical trials.

A pharmacogenetic versus a clinical algorithm for warfarin dosing.

Background: The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.

Methods: We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy.

Rationale and design of the Clarification of Optimal Anticoagulation through Genetics trial.

Background: Current dosing practices for warfarin are empiric and result in the need for frequent dose changes as the international normalized ratio gets too high or too low. As a result, patients are put at increased risk for thromboembolism, bleeding, and premature discontinuation of anticoagulation therapy. Prior research has identified clinical and genetic factors that can alter warfarin dose requirements, but few randomized clinical trials have examined the utility of using clinical and genetic information to improve anticoagulation control or clinical outcomes among a large, diverse group of patients initiating warfarin.

Electronic health records based phenotyping in next-generation clinical trials: a perspective from the NIH Health Care Systems Collaboratory.

Widespread sharing of data from electronic health records and patient-reported outcomes can strengthen the national capacity for conducting cost-effective clinical trials and allow research to be embedded within routine care delivery. While pragmatic clinical trials (PCTs) have been performed for decades, they now can draw on rich sources of clinical and operational data that are continuously fed back to inform research and practice. The Health Care Systems Collaboratory program, initiated by the NIH Common Fund in 2012, engages healthcare systems as partners in discussing and promoting activities, tools, and strategies for supporting active participation in PCTs.

Signposts along the NIH roadmap for reengineering clinical research: lessons from the Clinical Research Networks initiative.

Background: The National Institutes of Health (NIH) Roadmap for Medical Research aims to increase the efficiency and speed of clinical research. We report results and lessons learned from a key component of the Roadmap, the Clinical Research Networks initiative.

Methods: Twelve diverse, experienced, large, clinical research networks were funded for 3 years to develop strategies for integrating, expanding, and increasing the interoperability of clinical research networks in support of the Roadmap goals.

A randomized controlled trial of intravesical bacillus calmette-guerin for treatment refractory interstitial cystitis.

Purpose: We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC).

Materials And Methods: Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC, and reported at least moderate pain and frequency for a minimum of 6 months before study entry, were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34.