3D medical animation still shot showing structure of a coronavirus — Wikimedia, Creative Commons license
3D medical animation still shot showing structure of a coronavirus — Wikimedia, Creative Commons license
3D medical animation still shot showing structure of a coronavirus — Wikimedia, Creative Commons license

Experts, Evidence & Hydroxychloroquine

Always Be Evaluating Your Sources—Especially During a Pandemic

*Updated July 31, 2020 to include additional significant randomized studies, including those examining the use of hydroxychloroquine as a preventative measure

Can I provide an illustration of why it’s always important to consider evidence from multiple authoritative sources when studying subjects like COVID-19, the use of masks, and in this case, the use of hydroxychloroquine? Especially during this time of pandemic. (But, really, this strategy applies to any subject.)

If I were to look for something that initially seems compelling (as a non expert, non epidemiologist) on the efficacy of hydroxychloroquine in treating COVID, this Newsweek essay by Yale professor Harvey Risch certainly might grab my attention.

I read that piece and though some of it sounded compelling, it seemed to me like Risch was making some leaps in causality with his examples of Brazil and Switzerland. Turns out David Gorski—who knows the subject much better than I—was able to explain in great detail why those examples show a cause and effect fallacy but he also continued to break down how Risch references some really bad studies and to explain that Risch’s own work has been appropriately criticized.

Additionally — and more importantly — two studies on the efficacy of hydroxychloroquine came out the same day Risch published his piece, both of which included more participants than many of the questionable (sometimes even debunked) studies many keep referencing online.

  1. The first clinical trial with 667 participants was published in New England Journal of Medicine and showed hydroxychloroquine does not help patients with medium to severe cases of COVID. To reiterate: It didn’t work at all.
  2. The second trial with 293 participants was published in Clinical Infectious Diseases and involved non-hospitalized medium severity COVID patients and it also showed no effect. NO benefit. Not a little, not a lot. None.

“If you, your spouse, your mother gets admitted to hospital and is offered hydroxychloroquine, don’t take it.”—Prof. Martin Landray, Oxford University

You could look back to June, too, when Science Magazine wrote explained that three significant studies “dim hopes that hydroxychloroquine can treat or prevent COVID-19.” Of these three, a UK study of hospitalized patients showed that in a group of 1542 patients treated with hydroxychloroquine, 25.7 percent had died after 28 days, whereas 23.5 percent died in a group of 3132 who received typical care. That study lead Oxford’s Martin Landray one of the study’s principal investigators to conclude: “If you, your spouse, your mother gets admitted to hospital and is offered hydroxychloroquine, don’t take it.”

The other two studies Science highlighted showed that hydroxychloroquine isn’t likely useful in preventing COVID-19 either, unfortunately. The first study published in The New England Journal of Medicine showed there was no statistical difference among people who used hydroxychloroquine versus a placebo to prevent COVID-19. A second study of 2300 people in Barcelona, Spain also showed no statistically significant difference. Importantly, both of these studies were conducted as randomized trials and both included much larger samples than some questionable and/or clearly flawed trials of, say, 100 people.

Additionally, the National Institute of Health recently discontinued a clinical trial on hydroxychloroquine because they determined it simply lacked efficacy. Per their statement: “while there was no harm, the study drug was very unlikely to be beneficial to hospitalized patients with COVID-19.”

It’s also worth noting that a Henry Ford Health System study favored by hydroxychloroquine advocates suffers from some of the same cause/effect problems Gorski highlights in the Risch column. Per STAT News and Matthew Herper, the Ford observational study was retrospective, not planned and deeply flawed as it doesn’t randomize participants and didn’t account for factors such as the use of steroids, which do appear to help people already sick with COVD-19. Additionally, observational studies should be used to determine what randomized studies to run in the future, not to assume ultimate efficacy of a particular medicine. David Gorski details the problems with this study, too, and concludes, “There was never any evidence sufficiently compelling to justify using hydroxychloroquine for COVID-19 outside of the auspices of a clinical trial.”

All that said, I’m obviously not an expert but I would look to experts for their thoughts on the subject and be happy to adjust my thinking if real evidence were to amass that hydroxychloroquine really does help to treat COVID-19. However, it looks like the recent, better run studies are amassing to show that’s simply not true.

If hydroxychloroquine does prove to be helpful in treating people with COVID-19, you’ll see the CDC explicitly say so, the FDA reverse its opinion, WHO reverse their opinion, and masses of qualified physicians coming forward to say we should use it.

However, I don’t believe the CDC, WHO, FDA and NIH are all conspiring to ignore medical evidence just to make Donald Trump or other fans of hydroxychloroquine look bad.

Finally, before sharing information about articles, studies, or videos, such as the recent Breitbart livestream, it’s worth seeing who or what organization supported the effort and what their political affiliations are. In the case of the Breitbart debacle, the event was backed by CNP Action, a group of wealthy donors, who the Associated Press reported discussed recruiting pro-Trump doctors who would be willing to go on television to push for reopening the U.S. economy before safety benchmarks were met.

A lot of misinformation can be avoided simply by seeking out multiple sources on medical topics, which have been authored and reviewed by medical experts and organizations, not simply engineered by political strategists.

Robert A Stribley


Citations & Further Reading

Biesecker, Michael and Jason Dearen. “‘Pro-Trump’ doctors sought to push rapid reopening of economy,” Chicago Sun-Times, 19 May 2020.

Boulware, David R., et al. “A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19,” The New England Journal of Medicine, 3 June 2020.

Cavalcanti, Alexandre, B., et al. “Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19,” The New England Journal of Medicine, 23 July 2020.

FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems,” U.S. Food and Drug Administration, 4 April 2020. Last updated: 1 July 2020. News release.

Gorki, David. “Henry Ford Hospital hydroxychloroquine trial: Not good evidence that the drug works for COVID-19,” Respectful Insolence, 9 July 2020.

Gorki, David. “Yale epidemiologist Harvey Risch defends hydroxychloroquine in Newsweek — badly,” Respectful Insolence, 24 July 2020.

Herper, Matthew. “A flawed Covid-19 study gets the White House’s attention — and the FDA may pay the price,” STAT, 8 July 2020.

Kupferschmidt, Kia. “Three big studies dim hopes that hydroxychloroquine can treat or prevent COVID-19,” Science Magazine, 9 June 2020.

Mitjà, Oriol. “Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial,” Clinical Infectious Diseases, 16 July 2020.

NIH halts clinical trial of hydroxychloroquine,” National Institutes of Health, 20 June 2020. Media advisory.

Risch, Harvey A. “The Key to Understanding COVID-19 Already Exists. We Need to Start Using It — Opinion,” Newsweek, 7 July 2020.

Statement from the Chief Investigators of the Randomised
Evaluation of COVid-19 thERapY (RECOVERY) Trial on
,” RECOVERY, University of Oxford, 5 June 2020. [PDF]

Treatment of COVID-19 Cases and Chemoprophylaxis of Contacts as Prevention (HCQ4COV19),” ClinicalTrials.gov, 11 March 2020. Last updated: 30 June 2020.

WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19,” World Health Organization, 4 July 2020. News release.

Zadrozny, Brandy and Ben Collins. “Dark money and PAC’s coordinated ‘reopen’ push are behind doctors’ viral hydroxychloroquine video,” NBC News, 28 July 2020.

Writer. Photographer. Interests: immigration, privacy, security, human rights, design. UX: Publicis Sapient. Teach: SVA. Student: NYU’s Global Affairs program.

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