Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

When the Covid crisis is over, one of the strangest sub- plots will have been the fracas around Hydroxychloroquine. Starting from medical practitioners worldwide adopting its usage in a ‘cargo cult’ way, mimicking what other doctors were doing, to Raoult’s low- quality study. Then people in Silicon Valley (notably Elon Musk) picking up the idea. Followed by the explosion in the political sphere, from Trump pushing it at the White House podium, to Indian PM Modi reversing an HCQ export ban for Trump, to French PM Macron talking it up.

All the while HCQ remained unproven for Covid use, while people trying it got hurt by cardiac side- effects (and one couple in a prominent incident mistakenly took different chemicals with a similar name), and patients with other conditions ran out of HCQ due to shortages.

Maybe HCQ will be part of the standard of care for Covid- 19 in the future, but it’s seeming less and less likely. Meanwhile it’s definitely not a miracle cure, so the frenzied advocacy and adoption of this medicine will turn out to have been a bizarre story.

(I wrote this up here https://twitter.com/firasd/status/1250125344469708801)

> Lots of conflicting research happening

That's my main take-away at this point. I have seen enough reports saying it worked, and enough saying it didn't that I believe the answer is probably somewhere in the middle.

My understanding is the best guess for how it works is by keeping the viral infection from becoming serious enough to require hospitalization. Similar to how proper treatment of wounds early on keeps them from getting to the gangrene stage where you need amputation.

Unfortunately, politics. So the Left wants it to be completely no use at all, and the Right wants it to be a miracle drug. Most of the population really probably just wants effective treatments if they end up getting sick.

Yup - and said controversial political figure jumped on the guess before the science was in and heavily endorsed it - this is likely leading to widespread misuse of a drug which is know to cause extreme damage to organs including kidneys, livers and eyes when misdosed and taken in excess.

That study has been widely condemned as lacking any sort of rigour – the journal that published it has since issued a statement of concern around the methods.

For example, their "control" group were just arbitrarily-chosen patients treated at different hospitals, not people treated in the same hospital as where the study was conducted.

It's important to interpret these results carefully: "no evidence of efficacy" does not imply evidence of no efficacy, and in fact the uncertainty in this study is quite large. The sample size is small enough that it would be very hard for this study to detect the effect of hydroxychloroquine unless that effect is very, very large.

From the abstract:

> In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00).

The relative risks and confidence intervals are the important numbers here. For example, the relative risk for death is 0.61, meaning the observed risk of death was lower for patients treated with hydroxychloroquine -- but the confidence interval is 0.13 to 2.89, meaning the data is consistent with anything from the risk being much smaller to the risk being much larger. Since there were only 3 deaths in the treatment group and 4 deaths in the control group, it's very hard to draw precise conclusions about death rates.

I think we can interpret this result to mean that hydroxychloroquine doesn't have a miraculously large effect, but the evidence is weak. Other commenters are correct that large randomized trials will be more definitive.

(disclaimer: I am a statistician, not a doctor)