I have no problems with the way this test was set up. It was a quick study that would have told us quickly if there was a huge benefit from HCQ. That wasn't the outcome. Larger tests with better statistical power will tell us if there is a smaller positive effect. My point is, the smaller the beneficial effect, the larger the test will have to be to find it, but also the lower the overall benefit to patients.

Again, note also that more patients on HCQ were diagnosed with ARDS, so if you pick a different measure, you get the opposite result.

My immediate reaction was that I would not expect to see an effect if you are giving HCQ to patients after they have been hospitalized by the virus. You are now into the inflamation/cytokine storm phase of COVID-19. The best chance of HCQ working is very early, ideally before or directly after exposure. The jury is still out if you take HCQ after the onset of sympthoms if that is also too late. Based on this in-vitro study - https://www.nature.com/articles/s41421-020-0156-0 - if I hypothetically had both Chloroquine (CQ) and Hydroxychloroquine (HCQ), I would prefer HCQ for prophylaxis/pre-sympthoms, but if I was sympthomatic, I would choose CQ. The loading time or HCQ is longer and it appears less effective at higher MOIs "the data suggest that the anti-SARS-CoV-2 activity of HCQ seems to be less potent compared to CQ, at least at certain MOIs."

> The best chance of HCQ working is very early, ideally before or directly after exposure.

Adding to this, there are at least two reasonably sized ongoing trials of HCQ with appropriate randomization and blinding in North America alone (I believe there are a number of others elsewhere). I would encourage everyone to withhold judgement until either they post results, or a similarly reliable alternative data source appears.

Target size of 3000 (https://clinicaltrials.gov/ct2/show/NCT04308668).

Target size of 400 (https://clinicaltrials.gov/ct2/show/NCT04329923).

Can Minnesota really recruit 3k people in the next 2 weeks? The second Patch trial won't report until 2021.

Yeah I was wondering about that myself. There are 5 participating locations listed, but even then it's a large sample size and an aggressive time frame. On the other hand, just about any healthy adult who recently came into contact with a confirmed positive case is eligible to enroll so maybe it won't be so difficult under the circumstances?

For pre-symptomatic C19 patients, we're already doing a large-scale natural experiment, because HCQ is part of widespread protocols for common ailments like RA, and the dosages those patients get are comparable. As I understand it: we're admitting lots of RA patients with C19; there doesn't seem to be a huge effect with early dosages either?

Yeah, it's pretty clear there isn't a huge effect. But there may still be a big enough effect to move the needle. I have no knowledge of the RA/Lupus subgroup, so any anecdotes to share are welcome!

Problem with that is people with RA and Lupus are typically hyper careful about their health and most likely to be serious about self isolating.

I'll track down the source I read this from, but my claim was specifically that we are hospitalizing people with RA on HCQ already. So that doesn't really respond to what I said.

The French study (which kicked off the whole interest in this) was done after hospital admission.

(It was also mostly junk science of course too)