Written by: Brian Cole
In addition to providing patients with access to experimental therapies, the COVID-19 clinical trials now underway in Manitoba are also helping to enhance this province’s research capacity.
Dr. Ryan Zarychanski, a hematologist, critical care physician, and clinician scientist at CancerCare Manitoba and the University of Manitoba, is supervising eight clinical trials involving six therapies for patients who have or are at risk of getting COVID-19.
The disease, which is caused by severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, has killed more than 400,000 people around the world since emerging in China earlier this year. It is considered to be the deadliest pandemic since the Spanish Flu in 1918, which killed an estimated 50 million people around the globe.
As a result, researchers and physicians around the world are working to develop treatments and a vaccine against the virus. In Manitoba, Research Manitoba and the provincial government have provided approximately $1.6 million in start-up funding for clinical trials to test various treatments for the disease. More recently, Zarychanski’s team received about $5.8 million in funding from the Canadian Institutes of Health Research to help carry out the clinical trials.
The increased workload means that some relatively junior investigators on Zarychanski’s team, which includes more than 30 nurses, co-ordinators, investigators, physicians, trainees and medical students, are getting a chance to take on more responsibility. And that added responsibility is translating into valuable experience for local researchers as they move forward in their careers.
Dr. Lauren MacKenzie is a case in point. An infectious diseases physician and an assistant professor in the Department of Internal Medicine at the University of Manitoba, MacKenzie is also a PhD candidate in the Department of Community Health Sciences at the Max Rady College of Medicine. As the COVID-19 outbreak morphed into a pandemic, she was asked to take on more responsibility, first as a co-investigator in Manitoba for an international trial involving hydroxychloroquine, and then as the Canadian principal investigator for a second international trial involving the drug.
“That was really my first experience taking part in a clinical trial,” she says. “I learned a tonne in terms of the basic ins and outs of how a clinical trial works in the real world.”
One big lesson learned was just how quickly things can be done when there is a public health emergency, such as a pandemic.
“It really came down to a fantastic group of people at the University of Manitoba. And fantastic collaborators at McGill (University), the University of Alberta (for the first trial), and the University of Minnesota,” she says. “All of us were… just trying to tackle the problem at hand, which was, ‘Can we find a therapy that might be helpful in this pandemic?’”
Dr. Sylvain Lother is another research trainee on Zarychanski’s team. A critical care and infectious diseases physician, he is also working on a Master’s degree in community health sciences at the University of Manitoba. He says the need to launch several clinical trials all at once meant that researchers just starting out in their careers had an opportunity to become more deeply involved in various studies than might otherwise be the case.
“This is a once in a lifetime opportunity,” says Lother. “Typically, trainees are at a (facility) for only a couple of years… And so, if you started a trial early in your training, you would almost certainly be done your training by the time the trial was up and running. For that reason, most research trainees don’t typically get involved in randomized trials because you can’t finish it in (the) time frame that your training would occur over.”
But because of the urgency surrounding the pandemic, Zarychanski’s team was able to get trials up and running in a few weeks or months. “So that has presented me with a real unique opportunity to get involved, from start to finish, in (several) randomized controlled trials in a very short period of time,” he says.
Lother says he spends most of his days providing care to COVID-19 patients in the intensive care unit. The experience has underscored some crucial lessons, not least of which is the importance of integrating clinical trials with critical care, which essentially involves taking information gleaned from clinical trials and using it to immediately improve patient care or better inform questions being posed in a particular research project.
“The integration of research and clinical care is extremely important because our clinical observations are really what drives the generation of research questions, and the clinical trials should be what ultimately drives our clinical decision making,” he says.
As an example, he points to the international clinical trial on heparin that is being led by Zarychanski. The study was advanced, in part, because clinicians in Winnipeg and elsewhere noticed that many COVID-19 patients were getting blood clots.
“With COVID-19, we noticed that blood clots were happening at a larger rate than would be anticipated from other critical illnesses. So the question arises, ‘Well maybe if we gave people a blood thinner, than those people might do better,” he says.
Zarychanski says these individuals and others on his team represent the next generation of physician scientists in Manitoba.
“And because of the experience gained through their participation and leadership in the trials, our research capacity in Manitoba – that is our ability to articulate relevant research questions and complete clinical trials in non-COVID-19 conditions – will be increased for years to come.
And that, he says, will help promote the development of a culture of clinical research in Manitoba “where research is synonymous with good clinical care and where the outcomes or experience of every patient informs future clinical decision-making.”
Brian Cole is a Winnipeg writer.