Jasleen MahindruScott Garrison, professor of family medicine at the University of Alberta, recently concluded the largest randomized clinical trial ever carried out in primary care in Canada. The trial, BedMed, was done with the Pragmatic Trials Collaborative, a group of over 400 primary care providers.
Garrison was first inspired to form the Pragmatic Trials Collaborative during his own time as a family doctor when a patient noted that her leg cramps disappeared when she began taking medication for pneumonia.
“I ended up doing a small randomized trial to explore whether that was the answer. It wasn’t,” Garrison said. “But it got me really interested in pursuing that kind of question, and then I had realized that the outcomes that were already really important to patients and providers are already routinely being collected on everybody. If you could just get the physicians to randomize some simple things, you could ask these really important questions.”
Garrison later completed a PhD in experimental medicine in order to pursue such research and foster a “learning health-care system,” which became the Pragmatic Trials Collaborative.
Garrison built the team by sharing the project at primary care conferences like Practical Evidence for Informed Practice (PEIP), where he collected contact information from interested practitioners. Many doctors who attended these conferences virtually also signed up, spreading the Pragmatic Trials Collaborative to other provinces.
Pragmatic Trials Collaborative focuses on patient-oriented research
The team, including family physicians and nurse practitioners, now has participants from Alberta, British Columbia, Saskatchewan, Manitoba, and Ontario. They specialize in pragmatic trials which are overlooked by industry sponsors.
“We’re trying to pursue those really important trials inexpensively and by partnering with the Alberta Health Services (AHS) or what they call the SPOR data platform, which is support for patient-oriented research,” Garrison said.
“By partnering with [AHS] to use the administrative health data, you can conduct large trials extremely inexpensively, so it makes the kind of work that we’re trying to do very patient-oriented.”
Garrison said they look at “important topics that there’s no profit motive for anybody to be pursuing, but they could be hugely important to the individual.”
Their first trial, titled BedMed, studied whether it made a difference what time patients take their medication for high blood pressure. It responded to a 2010 Spanish study which found that taking such medication at bedtime led to a 61 per cent lower risk of heart attack, stroke, heart failure, and death.
“It never changed practice in large part because it seemed too good to be true,” Garrison said.
A subsequent British-based trial, titled TIME, found no difference, so the Pragmatic Trials Collaborative set out to do their own test.
Over 3,000 patients were recruited for this trial across five provinces, and were divided into two groups. One took the medication in the morning, and one in the evening. The trial took place from 2017 to 2022, with follow-up in 2023, though participants continued to join throughout the trial for varying lengths of time.
Ongoing trials include research on medication doses
BedMed was accompanied from 2020 to 2023 by another trial, BedMed-Frail, which used a similar design but focused on older, frail adults. BedMed-Frail engaged nearly 800 patients in 13 long-term care facilities in Alberta, and concluded its follow-up period in 2024.
“Frail older adults are very poorly represented in most randomized trials, and the risks and benefits can be very different in that population.”
Both trials had the same result: blood pressure medications taken at bedtime work just as well as those taken in the morning. As such, patients should choose based on preference, such as if their specific medication has a minor side effect.
Garrison and the Pragmatic Trials Collaborative have moved on to new trials, including OptimizeBP and MinMed. MinMed, which studies whether health outcomes for patients over 80 can be improved through reducing the amount and dosage of their medicines, has been on Garrison’s mind since he started building the team, but is more complicated than BedMed or BedMed-Frail.
“I’ve always been moving towards the MinMed trial, and the other trials before that, including BedMed, was … to bring the [doctors] in and give them an easy experience doing an important trial, and then we can move on to something which is a little more complex where we’re having visits to try to do this minimizing. So it’s sort of baby steps and creating the network.”
