27 Mar 2020 Randomized clinical trials are the only way to learn how we should treat COVID-19
“Hydroxychloroquine and azithromycin taken together have a real chance to be one of the biggest game changers in the history of medicine.” Tweet by President Donald Trump.
There are very few “game changers” in the history of prescription drugs.
During this global health emergency, demand for an effective treatment for COVID-19 is fervent. From the US President to his Twitter-feeding grassroots, people who weeks ago were COVID-19 deniers now demand “lifesaving drugs” to vanquish the pandemic.
Despite this urgency, we have no proven and approved drugs to treat COVID-19. Among proposed ‘game-changers’ is hydroxychloroquine, used for decades to treat malaria, and more recently rheumatoid arthritis, systemic lupus, and psoriatic arthritis.
This week the BC Centre for Disease Control, the College of Physicians and College of Pharmacists assessed proposed drug treatments. They concluded that none are recommended. They should be used only within approved, randomized, controlled trials.
The World Health Organization (WHO) has been working on this since COVID-19 was identified in January. Two weeks ago, WHO launched the SOLIDARITY randomized controlled trials of four potential drug treatments in multiple countries, including Canada.
Why is this needed? For over 100 years, medical scientists have known that without comparing an experimental treatment with a “control” (placebo or alternative treatment), we cannot know the impact of what we are doing.
Does this mean asking desperate people with potentially life-threatening infection to consent to being randomized to an unknown and unproven treatment? A reflex response might be to see that as unethical. However, it is even more unethical for doctors to order unproven, and potentially harmful treatments, when we have no idea whether we’re doing more good than harm. Oxygen, good nursing, and ICU support help the sickest patients. Beyond that, we don’t know. But medical science can quickly find out the truth.
Using science to identify treatments that work is ethical. The only available way to prove effectiveness scientifically is through randomized controlled clinical trials.
The late Dr. Tom Chalmers, a great American medical thinker, was an acknowledged leader in the design, conduct, and evaluation of clinical trials. In a 1995 interview with the Canadian Medical Association Journal, Dr. Chalmers referred to an “aha” moment early in his career. “I really did not question the pearls of wisdom from the experts until I got into practice. At some point I said to myself, ‘I’ve killed too many people.'”
Dr. Chalmers’ mantra was simple: “Randomize the first patient. If the choice or answer is not really known, then you have no business making a choice without studying it.”
In the ongoing WHO SOLIDARITY trial, patients randomly assigned to different experimental treatments will all receive the same high standard of care that has already saved the lives of many.
Everyone wants to see research “change the game” against COVID-19. And should we sicken from COVID-19, here at the Therapeutics Initiative, we too want to be randomized to a high quality, controlled, cooperative international clinical trial.
Ken Bassett MD, PhD and Colin Dormuth ScD
Dr. Bassett and Dr. Dormuth are Co-Directors of the UBC Therapeutics Initiative
“There are no proven therapies for the prevention or treatment of COVID-19. All agents have the possibility of associated harm, and pharmaceutical supplies province-wide and nationally for many of the possible agents are severely limited…for these reasons, the use of unproven therapies for COVID 19 is not recommended outside clinical trials. Unless there are patient-specific indications, these non-recommended therapies include:
- Lopinavir / Ritonavir (Kaletra®) –
- Chloroquine and Hydroxychloroquine
- Ribavirin and Interferon
- Other investigational therapies including ASC09, azvudine, baloxavir marboxil/favipiravir, camostat mesylate, darunavir/cobicistat, camrelizumab, thymosin, natural health products, and traditional Chinese medicines due to lack of data, lack of availability, or both.
These are consistent with other international advice, including WHO.