Wasn’t there a blockbuster study published two weeks ago that showed hydroxychloroquine *did* have a significant benefit for coronavirus patients? A study that grabbed the president’s attention and renewed calls from HCQ boosters like Peter Navarro, Laura Ingraham, and Rudy Giuliani for the FDA to once again authorize the drug for use in treating COVID?
There was. But that was an observational study. I’ve posted other observational studies that indicated no benefit from HCQ against the virus. The problem with observational studies is that the patients who receive the drug aren’t necessarily chosen at random, which means firm conclusions about what did and didn’t contribute to their recovery can’t be drawn as easily. Last week Stat published this critique of the “blockbuster” from the Henry Ford Health System that was touted by Trump:
Decisions [by the FDA] are based almost entirely on what is known as a randomized controlled trial, in which patients are randomly assigned to receive a treatment or not. Other types of studies have, again and again, failed to deliver accurate information about medicines’ benefits and risks, and are used sparingly in making medical decisions. Three randomized studies have now shown no benefit for hydroxychloroquine in hospitalized patients.
The study that sparked the latest controversy was anything but randomized. Not only was it not randomized, outside experts noted, but patients who received hydroxychloroquine were also more likely to get steroids, which appear to help very sick patients with Covid-19. That is likely to have influenced the central finding of the Henry Ford study: that death rates were 50% lower among patients in hospitals treated with hydroxychloroquine…
Nissen and Borio say observational studies simply cannot be used to determine whether a medicine is effective. Again and again they have been wrong.
The steroid dexamethasone *has* been shown in a randomized controlled trial to benefit severely ill coronavirus patients. If the patients in the Henry Ford study were getting HCQ and steroids, it may be that the steroids are what helped bring them back from the brink, not hydroxychloroquine.
What we need are randomized trials. Conveniently, results from two of them were published in the last day or so. One came from the UK’s RECOVERY project and focused on patients who’d reached the point of needing hospital treatment for COVID-19:
Patients who received hydroxychloroquine randomly were less likely to have been discharged from the hospital by the end of the study than patients who didn’t get it. The other study came from the University of Minnesota and focused on patients who didn’t (yet) require hospitalization:
We observed no effect of early outpatient therapy with #hydroxychloroquine in reducing symptom severity or duration. 56% enrolled within 1 day of symptom onset. Manuscript at: https://t.co/LcTlazPB79 pic.twitter.com/A5fnZtafoM
— David Boulware, MD MPH (@boulware_dr) July 16, 2020
#Hydroxychloroquine did not improve symptom severity or duration statistically faster than placebo in this double-blind randomized trial. No further benefit of zinc use (In the Appendix Table S2). pic.twitter.com/y1TXBmW8xl
— David Boulware, MD MPH (@boulware_dr) July 16, 2020
Yes, they tried giving the drug with zinc too. (And vitamin C.) That didn’t help.
But can we trust these studies? Some doctors are skeptical:
To conduct these studies, the researchers made significant compromises. They could not obtain diagnostic testing for all patients, so included people who had symptoms but couldn’t get a test result. In the end, only 58% of the people in this study had diagnostic test results. The researchers mailed study drug or placebo to patients without examining them after they enrolled over the internet, meaning they used data patients self-reported. In the end, the study randomized 491 patients, 432 of whom contributed data to the final analysis…
“The study was of such low quality that it was fundamentally uninterpretable,” said Steven Nissen, a veteran clinical trialist at the Cleveland Clinic. Still, he said, the evidence against hydroxychloroquine is mounting. “In this study there is no evidence of a benefit for hydroxychloroquine, and it is probably time to move on and start testing other therapies,” he said.
Hard to believe the FDA’s going to re-authorize HCQ without any randomized data supporting the drug’s efficacy. Maybe a future study will alter the balance of opinion, but it’s an open question at this point how many scientists will want to continue devoting resources to testing hydroxychloroquine when there are other, potentially more beneficial drugs coming online. The Times has a webpage set up to track the status of various COVID treatments: As of today, five drugs show strong evidence of working against COVID-19 and another three are “promising” but require further study. Hydroxychloroquine is now listed as “not promising.” Why spend money on running that experiment when you might get more bang for your buck elsewhere?
In lieu of an exit question, go read this Gizmodo post about the French study that ignited a global frenzy over hydroxychloroquine in March after it purported to show tremendous results in treating coronavirus patients with the drug. Various scientists have since shredded it for its methodological errors. Anthony Fauci’s skepticism about HCQ was the crowning indictment of his scientific expertise in the dopey op-ed published by Peter Navarro a few days ago.