MONTREAL — Quebec’s College of Physicians, the health ministry and scientists are urging doctors to proceed with great caution following a recent press release touting the effectiveness of colchicine, the only “oral medication for treating non-hospitalized patients, with COVID-19.”
“The results look good…and there is reason to believe it will have an effect, but there’s so much more of the story we’re missing,” Dr. Emily McDonald, a scientist at the MUHC’s Research Institute told CTV in an interview.
Late Friday night, the Montreal Heart Institute (MHI) announced the results of a study, saying they showed the medicine colchicine, an anti-inflammatory used to treat gout, reduced the risk of death or hospitalization by 21 per cent. The study enrolled 4,488 people.
But while it would be great news for people around the world if colchicine, an inexpensive, generic and available medication is indeed beneficial, the chief complaint is that no meaningful numbers were communicated in the press release to help scientists understand if that is true.
Compounding the concern for some – the press release hailed it as “a major scientific discovery,” and in an interview with The Canadian Press the following day Dr. Jean-Claude Tardif, the lead investigator and director of the MHI, said, “any doctor, tomorrow, who reads this can definitely decide to prescribe if he wants.”
But McDonald and other colleagues say it’s just too early to make those claims with such conviction since the study hasn’t yet been peer-reviewed and published by a scientific journal.
“I’m not, ‘oh, I don’t buy it’,” Ashish Jha, dean of the Brown University School of Public Health in Rhode Island, was quoted in a story on the MHI announcement, published on the health and science site STAT.
“It’s possible. There’s enough plausibility here,” said Jha. “This could be a real finding, and if it is, that would be great. But this press release doesn’t get us there.”
There’s also confusion about what the press release did say. “Did it reach statistical significance? We’re not quite sure,” said McDonald, since the press release also suggests some results “‘approached’ statistical significance.”
‘ENCOURAGING’, BUT ‘PRELIMINARY’: DOCTORS ASKED TO BE PRUDENT
Quebec’s College of Physicians and the Order of Pharmacists reacted quickly after the Montreal Heart Institute’s announcement on Friday, sending out a memo two days later, asking their members to steer clear of colchicine for now.
The warning appears to be a response to a sentence in the MHI press release saying patients at risk of complications can be treated with colchicine “as soon as the diagnosis of COVID-19 is confirmed by a PCR test.”
However, the College of Physicians asks doctors “to act with great prudence if they are considering prescribing colchicine to patients who have COVID-19 until they receive clear directives.”
Pharmacists will not be permitted to dispense colchicine if the drug is prescribed for someone as a precaution, in the event they eventually test positive for COVID-19.
The orders’ statement also called the results of the clinical trial “encouraging” but “preliminary,” because the data haven’t been formally analyzed and published.
They noted that Quebec’s Health Ministry and the National Institute for Excellence in Health and Social Services were involved in the discussion.
Some doctors came to those same conclusions, the day the scant details were made public.
One family doctor in Montreal, who preferred to remain anonymous, told CTV by email that “he would not be comfortable prescribing colchicine for COVID-19 at this time.”
SEEKING SAFETY INFORMATION
How is colchicine used now?
- An anti-inflammatory medication used to treat gout, and a rare illness called familial mediterranean fever
- Used off-label to treat pericarditis, an inflammation of the sac around the heart
When a drug is used in a new way, however, it also has to be evaluated for new harm, according to researcher Dr. Emily McDonald.
“We knew how to prescribe colchicine for gout yesterday, but that doesn’t mean we know how to prescribe it for COVID today.”
And while colchicine usually causes only mild side effects including diarrhea and nausea, McDonald says it can in rare instances be toxic and even fatal if a person is prescribed too high of a dose.
It can also be contraindicated for someone with certain kidney problems and can interact with common drugs like certain antibiotics or blood pressure medications.
“So, we need to wait for proper results [in a published study] before we prescribe it widely. Even a drug with a few side effects becomes more problematic when given to a very large population,” said McDonald.
She cites the hydroxychloroquine study at the R-I-MUHC that she co-authored as an example. Like colchicine, it was a repurposed medication and safe for other uses but was discovered to cause cardiac arrhythmia when used to treat patients with COVID-19.
“There are just so many steps in the scientific process before we can say this is a medication that is going to make a major difference in the world and in the pandemic.”
McDonald says she thinks once a manuscript is submitted, it will take about two to three weeks to get some answers. Science journals and reviewers have cut out the red tape, to respond to the urgency of the pandemic.
NUMBERS, NUMBERS, NUMBERS
Participants in Canada, the United States, Europe, South America and South Africa took part in the large randomized, controlled colchicine study.
The researchers provided four percentage figures to the public last week, to highlight the various reductions in deaths, hospitalizations, and the need for mechanical ventilation.
But those numbers don’t offer enough insight, says McDonald, who is also an internist at the MUHC.
“I think if you are going to release a number you should probably give the upper and low number around it – that’s the confidence interval. So, these numbers were released without the statistics around them,” and that means scientists can’t interpret the results, she said.
And seeing more “absolute” numbers would be more helpful than “relative” numbers, McDonald said.
“You can imagine reducing two complications to one complication is very different from reducing 200 to 100.
If all you show is a relative decrease of 50 per cent, that’s missing information that would help us know whether it’s important to patients.”
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