There have been no substantial advances with new antivirals, and remdesivir, a drug approved for use in hospitalized patients, has had only a modest effect in curbing bad outcomes. We are in desperate need of safe, oral medications to treat early cases of covid-19 to prevent hospitalization and death.

Unfortunately, the debacle with hydroxychloroquine in the summer, touted by the former charlatan in chief as a cure-all for SARS-CoV-2 infection, further poisoned the well of repurposing old and generally safe medications for treating the new disease.

But potentially reliable medications are available already — and it’s time to start trying to use them, even if that means loosening the standards for deciding whether a drug works to use off-label to treat the coronavirus.

Last week, the Montreal Heart Institute issued a news release sharing encouraging findings from a study of the anti-inflammatory medication colchicine in reducing covid-19-related hospitalizations or deaths. Colchicine is a an inexpensive and safe medication that had been on the World Health Organization list of essential medications for the treatment of gout until 2005, when it was replaced by nonsteroidal anti-inflammatories such as ibuprofen. While the news release suggested a 21 percent reduction in death or hospitalizations, the actual number of those events was very small (fewer than 10, total), resulting in findings that are statistically fragile.

In the United States, a randomized-controlled study, the type of study design believed to produce the highest, unbiased quality of evidence, demonstrated that the drug fluvoxamine, a medication approved by the Food and Drug Administration to treat depression more than 25 years ago, significantly reduced clinical deterioration — including preventing 100 percent of hospitalizations — in patients newly diagnosed with covid-19. An observational study just reported by its research sponsor last week, and conducted during a covid-19 outbreak among employees at a racetrack in California, replicated those findings — a 100 percent reduction in hospitalization or death — from six hospitalizations or death among untreated patients compared with none among fluvoxamine-treated patients.

At least 1,000 patients have died every day of covid-19 since mid-November. With the ongoing devastation and the burden on hospitals, families and medical personnel, what evidence is needed before we can conclude that the benefits of a medication outweigh its risks? How much certainty is needed if the alternative — no treatment — guarantees hospitalization in 10 to 20 percent of known cases and deaths in 2 percent?

The 21st Century Cures Act, signed into law by President Barack Obama in December 2016, includes Section 3022, which requires such institutions as the FDA, the Centers for Disease Control and Prevention and NIH to consider “real world” evidence in assessing medications.

As I have learned and studied the mechanisms of fluvoxamine action in cellular, animal and clinical research studies, as an infectious-disease physician and public health expert, I have struggled with the questions of “how much evidence is enough” and what is “real world evidence.”

To further understand a way forward, last week, I invited a select group of clinical, pharmacology and statistical experts from academic, public health and U.S. governmental research institutions to review and discuss the data on fluvoxamine. I asked them to consider the question: In the absence of the most robust evidence, are we ready for a process sometimes called “shared-decision making” between a physician and patient? That would involve the physician providing the patient with the pros and cons of an intervention to enable the patient to make their own informed choice. In the case of fluvoxamine, there is a safe and promising oral medication that might prevent hospitalization and death. But it hasn’t yet passed the rigor of the highest bar of scientific evidence for efficacy — a large, rigorous randomized-controlled trial.

I was surprised to learn that among the 20 respondents, 11 supported “shared decision-making,” while only five opposed it and four neither opposed nor supported it. But perhaps that should be expected, given the increasing shift toward patient autonomy and the severity and extent of the epidemic.

So where does that leave us? From the physician perspective, with the overarching ethic for our profession being “Do no harm,” the use of a safe drug for 10 days is unlikely to be harmful for an individual and may have substantial benefit. The choice seems easy: Give it a try.

From the public health perspective, we might be recommending the use of a drug with no benefit to hundreds of thousands of scared individuals. It would be wasteful and misleading, at best, undermining the foundation of trust on which the field is built.

For me, personally, as one who is both an academic public health expert and physician, I am not ready to see fluvoxamine recommended in national treatment guidelines just yet. But I am ready to try it with individual patients who are at increased risk of bad outcomes. That’s the balance we’ll have to strike, one treatment at a time, as we try to find our way out of this pandemic.



Source link