Pragmatic Trials Services

Pragmatic Trials Services, offered through Schulich School of Medicine and Dentistry at Western University focuses on streamlined trials testing solutions, which are simple, scalable, and sustainable. Pragmatic Trials provide the same quality evidence as traditional trials in less time and at a substantially reduced per-patient cost. Pragmatic Trials Services provides ‘disease-agnostic,’ services to researchers interested in designing and implementing large scale pragmatic trials, including, protocol development and refinement, analysis of existing administrative data sources, human resources and governance planning, trial management, budget creation and monitoring, contract creation, quality assurance, and publication preparation.

HDRN Pragmatic Trials Training

The HDRN Canada Pragmatic Trials Training Program helps health researchers, post-doctoral trainees and highly qualified personnel gain the skills and experience needed to lead, design and implement high quality pragmatic trials in Canada. Pragmatic trials are a critical component of health care research because they are embedded in routine care and leverage real-world data sources. Done well, they yield valid, generalizable results faster than traditional trials at a fraction of the cost, yet few researchers in Canada have the training and experience to conduct pragmatic registry trials. The HDRN Canada Pragmatic Trials Training Program creates a pipeline of researchers in Canada who are well positioned to efficiently evaluate interventions, from drugs to vaccines to health technologies. The program is funded through the Canadian Institutes of Health Research and led by Dr. Amit Garg, Associate Dean, Clinical Research in the Schulich School of Medicine & Dentistry at Western University.

Dial-Mag

The Dialysate Magnesium Pragmatic Trial (Dial-Mag) is a multi-centre pragmatic cluster randomized trial being conducted in 150+ dialysis units located across Alberta, British Columbia, Manitoba, and Ontario. The trial team seeks to determine the effect of a higher vs. lower dialysate magnesium concentration (0.75 mmol/L vs. ≤0.5 mmol/L) on all-cause mortality, muscle cramps, fractures, cardiovascular-related mortality, and cardiovascular-related hospitalization. Previous studies indicate an association between a low serum magnesium concentration and poor outcomes in patients receiving hemodialysis. Increasing the dialysate magnesium concentration increases patients’ serum magnesium concentrations and may improve patient outcomes.  

As a patient partner-initiated outcome, all patients receiving maintenance hemodialysis are asked to voluntarily complete a single question twice a year about the severity of their muscle cramps. A designated dialysis staff records self-reported responses of cramp burden on a 0-to-10-point scale. Responses are provided to research staff on a tracking sheet without patient identifiers.

The trial protocol was developed through collaboration with patients, practicing nephrologists, ethics specialists, experienced statisticians, trial methodologists, a dialysis program manager, dialysis directors, and the Institute for Clinical Evaluative Sciences (ICES). For more information, please visit clinicaltrials.gov (NCT NCT04079582) or www.dialmag.ca.

Dialex

The dialyzer is a critical component of hemodialysis treatments, yet little evidence is available to determine which type of dialyzer could result in better patient health. There are various types of dialyzers used in hemodialysis units across Canada including “conventional” high-flux dialyzers and “expanded” super high-flux dialyzers. Previous research suggests that super-high flux dialyzers are more efficient at removing a wider range of wastes and toxins from the blood. To definitively assess the major health effects of expanded hemodialysis compared to conventional high-flux hemodialysis, a large, randomized controlled trial is needed. If results demonstrate improved outcomes, this trial could inform clinical practice, and expanded hemodialysis could become more widely available to patients’ receiving hemodialysis.

DIALysis with Expanded solute removal (DIALEX) is a large, simple, pragmatic trial to assess the major health effects of expanded hemodialysis compared to conventional high-flux hemodialysis. The trial design features streamlined eligibility and enrollment using an opt-out consent method (approved by the Western University HSREB) as well as outcome data ascertainment using administrative healthcare databases. The trial protocol was developed through collaboration with patients, practicing nephrologists, ethics specialists, experienced statisticians, trial methodologists, a dialysis program manager, dialysis directors, and organizations like Statistics Canada and the Institute for Clinical Evaluative Sciences (ICES). For more information, please visit clinicaltrials.gov (NCT 06660277) or www.dialex.study.

MyTEMP

MyTEMP was a pragmatic trial spanning four years, conducted across 84 hemodialysis centers throughout Ontario from 2017 to 2021. The trial examined the impact of a personalized cooler dialysate (0.5°C to 0.9°C below the patient’s pre-dialysis body temperature) versus the standard dialysis temperature of 36.5°C temperature dialysis on cardiovascular-related hospital admission or death. The MyTEMP determined that adopting a centre-wide policy of personalised cooler dialysate versus a standard dialysate temperature of 36.5°C did not reduce the risk of major adverse cardiovascular events or death. MyTEMP also included a sub-study, MyTEMP PRO, focused on examining patient self-reported symptoms. MyTEMP PRO found that patients in the personalized cooler dialysate temperature group were more likely to report feeling uncomfortably cold than in the standard group.

MyTEMP was the largest trial of maintenance hemodialysis published to date. It included over 95% of patients receiving hemodialysis in Ontario during the trial period. This totaled more than 15,000 patients who had more than 4.3 million dialysis treatments. More details can be found in the MyTEMP Protocol, MyTEMP Statistical Analysis Plan, and MyTEMP Findings publications.

Gardener’s Grove

The Gardener’s Grove Conference, held on March 27 – 30, 2023, focused on increasing knowledge and awareness of pragmatic large-scale randomized controlled trials (RCTs) embedded into routine hemodialysis care. This conference created a space for nephrology patients, providers and healthcare policymakers to plant, cultivate and nurture support for new trial ideas. 155 registrants across eight provinces and seven countries attended, providing attendees with the opportunity to gain a comprehensive understanding of pragmatic trials and their importance in improving hemodialysis care.

Over four days, ten educations sessions, and six structured panel presentations, were presented. Educational sessions were presented by seventeen experts covering a range of topics including Pragmatic RCT study design, statistics, ethics, and inclusion, diversity, equity, and accessibility (IDEA). Panel presentations provided researchers with an opportunity to present their proposed trial ideas to a highly educated panel for feedback. The conference facilitated excellent group discussions and expert panel feedback. Recommendations provided by highly educated panelists during the Gardener’s Grove conference shaped the design and implementation of several large scale pragmatic trials, including Dial-Bicarb and Dialex.