“In my opinion, hydroxychloroquine should not be used in the hospital setting,” says Martin Landray, a physician and researcher at the Nuffield Population Health Department at the University of Oxford and one of the chief recovery officers. “Outside of the hospital setting, it would be reasonable to use it in the context of a randomized controlled trial, but not otherwise.”
Speaking of which: The Minnesota study looked at people who are not in the hospital, so they are by definition not as sick. And that caused some methodological problems. Lack of quick and easy Covid-19 tests in the US meant that not all members of the study population obtained a diagnosis using PCR tests, or took a sample with a nasal swab and analyzed it for material virus genetics. For these participants, the team of researchers confirmed that they had symptoms similar to those of Covid and that they had contact with someone whose infection I was confirmed with a test. It is a slightly dicier configuration, but it is still valid.
Originally, the Minnesota team intended to use death or hospitalization numbers as a marker of whether the drug helped people in the study. But even though the number of both is very high in the US, actual mortality and hospitalization rates overall are low, or too low to show significantly in just under 500 people, the group size in the study. So without looking at the data, the team switched to another metric: reducing symptoms. (Participants reported their own symptoms on a 10-day visual scale on a day-to-day basis, the most common being cough, fatigue, and headache.) Here, too, hydroxychloroquine made no difference. Two weeks after starting, 24 percent of the 201 people who took the drug still had symptoms compared to 30 percent of the 194 people who took a placebo. Again: there is no significant difference.
Those results were actually going to be part of an earlier team paper, which showed that hydroxychloroquine didn’t work as a preventive, either, preventing people from getting sick after being exposed to the disease. This “post-exposure prophylaxis” document was accepted in the New England Journal of Medicine quickly and came out in early June. But as time went on and the drug faded a bit from the news and presidential reports, it was harder to find a home for the newspaper on how the drug fared as a treatment. “I guess the negative fact that hydroxychloroquine didn’t work was not so newsworthy. They weren’t that interested in a null study, ”says David Boulware, the infectious disease doctor who heads the team. “Designing the study took eight or nine days. Doing the study was seven weeks. Actually, it took two and a half months to publish … In a normal time frame, that’s fast. In a Covid period of time, that’s glacially slow. “
The lack of confirmed PCR-based tests also makes the study a little less bomb-proof. “True believers will criticize him. Not everyone had PCR tests, because it’s the United States and people didn’t have access to PCR tests, “says Boulware.” It’s not a perfect study, but I think it’s correct. “
By “true believers,” Boulware refers to people who remain firmly convinced of the drug’s value. For months, they analyzed each study of hydroxychloroquine for factors they think could influence its effectiveness that the researchers did wrong: too high a dose, too low a dose, administered too soon, administered too late, administered without supposedly important supplements such as zinc. Advocates of the use of the drug have proposed all those critics for its success. In some ways, they are right: dosage does matter. A major study of the drug in Brazil was stopped early due to serious heart problems in people taking it, a known side effect. But that study was also using extraordinarily high doses, far beyond levels used preventively or even as treatment. The Recovery and Minnesota teams used a more typical protocol.
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