Updated: Feb 12, 2021
Original author: Fahad Razak and Arthur Slutsky
Published: November 24, 2020
Fahad Razak is a general internist at St Michael’s Hospital and assistant professor at the University of Toronto. Arthur Slutsky is a clinician-scientist at St. Michael’s Hospital and professor of medicine at the University of Toronto. Both are members of Ontario’s COVID-19 Science Advisory Table.
We are in the midst of a second wave of COVID-19, and in the past few weeks we have reached two ominous milestones: the highest daily case numbers since the pandemic onset and crossing the ignoble marker of 10,000 Canadians who have died from the disease. Yet despite the most intense research focus in human history, there is only a single clearly effective treatment that reduces both symptoms and mortality: the steroid dexamethasone, based on the United Kingdom’s landmark Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial.
It’s a mistake to think research and clinical care are not one and the same. Clinical trials have the potential to help improve care and save thousands of lives. Canada can be a leader in the development of treatments for COVID-19 by developing the right plan, and by following the U.K.’s example.
What made the RECOVERY trial possible? Early in the pandemic, the U.K.’s National Institute for Health Research decided that hospitals must work together to test various therapies for COVID-19. A handful of the most promising randomized trials were chosen as key national priorities – RECOVERY was one of these. Simultaneously, the chief medical officers of the U.K.’s four historic countries strongly discouraged the use of any drugs not proven to be effective, other than in the context of a trial.
The impact of these decisions was striking – one in six hospitalized patients with COVID-19 in the U.K. was enrolled in a trial, dramatically higher than any other clinical trial for a major disease.
RECOVERY simultaneously tested several drugs for COVID-19; one of these was dexamethasone. Contrary to many trials, RECOVERY used a simple recruitment process and procedures to reduce the burden on health care staff.
By keeping the trial within the U.K., RECOVERY took advantage of a unified ethics and regulatory framework to receive rapid approvals. In contrast, other large trials, such as the World Health Organization’s multinational Solidarity Trial, were initially hobbled by requiring approvals in each local setting.
The U.K.’s deliberate approach allowed RECOVERY to make remarkable progress. Despite the intense pressures of the first wave of COVID-19, 176 hospitals contributed patients, with recruitment rates as high as 80 per cent. The dexamethasone arm of RECOVERY took a scant three months to complete, recruiting more than 6,000 patients. Trials of this size normally take years to complete.
We believe Canada is extraordinarily well positioned to conduct trials such RECOVERY. First, the scientific talent is already here. Canadians were the co-creators of the concept of large, simple and highly impactful trials. Canada is also home to some of the most prolific trialists worldwide; with only 0.5 per cent of the world’s population, we are ranked third globally (behind only the United States and U.K.) for producing ground-breaking trials.
Second, many provinces have incredible repositories of real-time electronic clinical data that could be efficiently used for research. For example, the eHealth Ontario data streams already contain much of the data that would otherwise require time- consuming and expensive manual collection for a trial. Current regulations only allow the bulk of this data to be used for patient care, but the pandemic should be the catalyst for legislative changes allowing other appropriate uses.
Third, Canada’s multi-ethnic population and single-payer health system means we have a diverse population with access to health care who could participate in trials. Research findings generated here are therefore not only optimized to our population but are also of high value globally.
So, what steps are required? First, given that delivery of health care is largely under provincial jurisdiction, provincial ministers of health must work with health care institutions to make trials a priority despite – and indeed because of – the pressures of COVID-19 care. In the U.K., this came in the form of a public-facing government directive that set lofty goals: “It should be the default position that every eligible patient is offered enrolment into a trial.” Second, existing federal bodies such as the Canadian Institutes of Health Research or the federal COVID-19 Expert Panel could develop mechanisms to choose priority studies. Third, funding should be made available to develop, co-ordinate and carry out the trials.
Trials like RECOVERY would be incredibly valuable to Canadians if conducted here. As detailed in Canada’s 2017 Fundamental Science Review, Canadian-led breakthroughs in medical sciences can improve our health and well-being, bolster our universities and research hospitals, strengthen our reputation in the global competition for resources and talent, and result in economic benefits for Canadians. And, most importantly, these trials could quickly develop novel therapies for treating COVID-19 while creating the downstream benefits of infrastructure and know-how to help us discover treatments for the next pandemic as well as for other diseases.