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Where is the proof of inefficacy? For the record, there's no proof of efficacy either, because all the trials done that prove or disprove efficacy of hydroxychloroquine were flawed in one point or the other (at least the ones I've read).

To give an answer to this endless debate, a proper, randomized clinical trial is needed. And the conditions set correctly, too: lopinavir and ritonavir were, per NEJM, not successful, but a later study in Lancet showed that administration at earlier time points (within 7 days of symptom onset) might be working and needs more investigation.

I know Novartis is running a trial, and so is U of Minnesota[1] which has finally completed enrollment and will release results after peer review.

Oh, and more on topic, it looks like Twitter has blocked a legitimate page of the Canadian part of the same group of trials[2].

[1] https://covidpep.umn.edu/

[2] https://twitter.com/DrToddLee/status/1261442201369939968

> Where is the proof of inefficacy?

It doesn't work that way. New drugs are assumed ineffective until proven otherwise. A government official with no medical training recommending an unproven drug based on a few anecdotes is the height of irresponsibility.

The null hypothesis is that it does not work, not the other way around. There is no need to prove inefficacy.

Currently the studies can't tell if HCQ is effective or not because all of them have been wasted opportunities for many different reasons, from too few patients, to absence of controls, to too late administration (the NEJM paper and the Lancet paper on lopinavir/ritonavir tell important lessons on this topic). We're in the "absence of evidence is not evidence of absence" territory.

I would say HCQ is a "lead" in the pharmacological sense (after all there's an effect in vitro), but of course there's no guarantee it will work properly (work as in "higher efficacy than placebo or other treatments") in vivo.

The reason for my comment is that the announcement by the "government official" (who was not the first, the first being the eccentric Dr.Raoult) turned what should have been scientific debate into a political flamefest (at least in the media). And science (aka, proper, randomized clinical trials) got lost in the way (at some point the U of Minnesota trial struggled to get new people).

I personally don't have any particular love for HCQ: chances are, like remedisivir, that if there is an effect, it is small. But I want to point out that so far science is still out on this one.

> Where is the proof of inefficacy?

This is a really odd idea. Drugs are normally assumed ineffective until proven otherwise.

> I would say HCQ is a "lead" in the pharmacological sense

Agreed. I hope it gets proven effective too. This is a hot button issue for me because a family member needs HCQ for lupus and now cannot obtain it because of the statements of said government official. His words have caused actual harm, and this isn't the first time.

Studies are coming in daily showing no benefit from HCQ. As this article [1] points out, any other drug would not be looked at further given the current set of information. But, since HCQ has been seen as a cure, a lot more time and money will be spent showing the same results - no effect.

[1] https://theness.com/neurologicablog/index.php/no-benefit-fro...

Most of these are retrospective and observational, and they fail to answer the question posed by the very controversial (and flawed) Raoult paper: that is, that early administration during the course of the disease provides a clinical benefit. Also in many the control is standard of care, which can mean everything and nothing.

The positive studies suffer from the same issues, by the way. Especially controls are pretty bad.

These studies can't give the answers that a proper randomized controlled trial (against placebo), like the U of Minnesota one (but there are a few others) can.

Some studies focus on mortality, but I doubt HCQ helps there: like remedisivir, the measure should be time to symptom clearance / hospital discharge. Time of administration also matters a lot (see again the NEJM paper on lopinavir / ritonavir, a failure, then the Lancet paper that gives more insight at earlier time points). One study I've read gave HCQ at 16 days post symptom onset (median): that time is definitely too late for any antiviral therapy.

I reiterate: I have no personal interest in having HCQ succeed. What I want to see is good science.