France, Italy, Belgium stop hydroxychloroquine use for Covid-19 on safety fears

https://www.reuters.com/article/us-health-coronavirus-hydroxychloroquine/france-bans-hydroxychloroquine-to-treat-covid-19-amid-safety-concerns-idUSKBN233197

by pseudolus • 6 years ago

114 94 6 years ago

reuters.com

lbeltrame10• 6 years ago

A shame, since the Lancet paper has problems[1][2] in particular related to the baseline of the HCQ-treated vs non-HCQ treated patients. And by admission of the authors themselves, it is not a substitute of a RCT.

And this before the results of the Minnesota trial are out. At this point I hope those are negative, so that it does not show that countries are overreacting.

[1] https://statmodeling.stat.columbia.edu/2020/05/25/hydroxychl... and related posts

[2] https://twitter.com/StevePhillipsMD/status/12638995692528967...

PS: The title is misleading. The ban is on the use on severe diseases, not all of them, according to the text in the news.

orwin• 6 years ago

Yes, i'm not a proponent of HCQ, not without RCT as some of my previous post might tell you, but the "raw" data of the Lancet study seems pretty well harmonized for raw data, i wouldn't trust this study for my national policies.

I can't take HCQ as i already have extrasystole and a allergies treatment that already can cause arythmia, so i hope this won't be the "best" treatment, but really this paper, while interesting, should not be used to take decisions.

lbeltrame10• 6 years ago

As I wrote elsewhere (check my post history) I personally think that if the effect is there, it is small. I don't really mind if HCQ doesn't work, but I get mad when people say "follow the science", and the most basic thing to do for science (a RCT) is not done.

Let's see if the U of Minnesota trial is published soon. The PI of the study tweeted he had sent revisions to the manuscript, and hoped for a publication this week (and he however added that he thought the same last week).

pen2l• 6 years ago

Lancet isn't the only paper that has raised issues with HCQ treatment.

Sciencemag [1] has this to say:

However, both HCQ and AZ have potential cardiac toxicity (QT prolongation, which can lead to fatal arrhythmia), and HCQ additionally has the potential for negative effects on the eye. Understanding risk-benefit ratios is paramount if these drugs are to become a standard of care for COVID-19. Several post hoc analyses carried out in the United States and Europe suggest modest benefit, at best, from HCQ monotherapy for COVID-19 patients; one large post hoc analysis among U.S. veterans suggests that there is harm to patients from HCQ. Given the mechanistic rationale but lack of well-designed clinical studies and potential for drug-induced toxicity, there is a key need for controlled, randomized trials to test the efficacy and safety of these drugs for COVID-19 patients.

[1] https://science.sciencemag.org/content/sci/368/6493/829.full...

I don't think it's a "shame" that some have decided to stop wtih HCQ when other viable treatments seem to have less concerning side-effects. Either way, we will know very soon with greater certainty as ongoing randomized trials finish up.

lbeltrame10• 6 years ago

Most of these analyses were done in late-stage COVID-19 patients, when any antiviral won't work (same results with remedisivir, lopinavir/ritonavir/ribavirin), that's why the discussion won't stop. Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus.

And guess what, no one (save the U of Minnesota trial, AFAICS) has done a RCT on that.

EDIT: I think it's a "shame" because all analyses so far focused on the late-stage disease, as I said, and because hopefully real RCT results will be out soon (like, real soon, or so I hope).

cataflam• 6 years ago

PS: The title is misleading. The ban is on the use on severe diseases, not all of them, according to the text in the news.

And the RCTs are still going and will finish, unless there is a major negative effect noticed in them, which is not the case so far.

lbeltrame10• 6 years ago

Indeed, there is hope that a definitive answer will come out (at this point, given how politicized the discourse is, any answer in either direction willl be fine).

FTR, the U of Minnesota trials used normal dosages and (according to its PI) did not report any cardiotoxicity so far.

acallaghan2• 6 years ago

If it had any effect on covid-19, it'd be very obvious by now. There isn't some massive conspiracy here, it just doesn't work. The reason trials have stopped is because France, Italy, Belgium & the UK have seen worse outcomes generally, directly because of it.

I don't get the 'it needs to be taken before symptoms!' argument - like we can possibly give a immunosuppressant with non-negligible side-effects (e.g. arrythmia) to billions of people with no scientific evidence of it working on covid at all.

zackees3• 6 years ago

It HCQ doesn't work, why is it the common first line of defense used internationally? Why does scholar.google.com list so many papers showing that it's effective?

lbeltrame10• 6 years ago

Not before symptoms, but after exposure, or early on during the course of the disease, like other antivirals.

I reinstate, before people think I'm some sort of HCQ defender: I am not. The effect size is probably very small. It may be as well that it doesn't work, and I would be happy even if it doesn't.

I just want to see a proper RCT done and sealed.

cm21876• 6 years ago

The first symptoms aren't necessarily the shortness of breath. In my case I had a week of mild fever before the shortness of breath kicked in. Fever isn't severe. Difficulty to breath is. You can have a policy to be treated when you get the first symptoms, but before these symptoms are severe.

dehrmann• 6 years ago

If it had any effect on covid-19, it'd be very obvious by now.

Not directly in response to this, but a broader observation I ran across was that lockdowns effectively shut down a lot of data creation (infections) about the virus, so there are still a lot of things we don't know, it makes it hard to make informed decisions.

rurban2• 6 years ago

It's obvious since end of February that the only usage is in prevention. Give to all risk persons 3 weeks before. That's the Indian advisory:

https://www.icmr.gov.in/pdf/covid/techdoc/V5_Revised_advisor...

dpoochieni6• 6 years ago

Haha, then why did China, Russia and Japan use it so successfully? Let's not forget we live in geopolitically very interesting times, and that the WHO is pretty much under the influence of China.

halflings2• 6 years ago

Agree this isn't an RCT, but why would this be an "over-reaction"? It's not like the default reaction is to administrate millions of doses of a medicine that has yet to be proven effective. (and could potentially do more harm than good)

The studies supposedly proving HCQ's effectiveness have much bigger caveats (tiny sample size and/or manipulation of the groups in a dishonest way, like Raoult removing severe cases from the treatment group whereas the control group had none)

lenkite2• 6 years ago

“India has so far made the right decision on HCQ and that this decision has been based on evidence,” Preeti Sudan, Secretary, Ministry of Health and Family Welfare, was quoted as saying by The Hindu.

The government late last week extended the use of HCQ for paramilitary and police personnel involved in COVID-19 management, besides direct health care providers for positive patients.

Soumya Swaminathan, Chief Scientist at WHO also told The Hindu that WHO is not advising stopping all HCQ trials but has only dropped HCQ from the Solidarity Trial, and that many prophylaxis trials using HCQ are ongoing or about to start.

OneGuy123• 6 years ago

"coronavirus is what happens when you put the reproducibility crisis in charge of the planet"

umvi2• 6 years ago

-- @mwilcox[0]

[0] https://twitter.com/mwilcox/status/1260458110596120576

0xcafecafe• 6 years ago

Can someone please elaborate on this? What is the "reproducibility crisis" in this case?

xapata3• 6 years ago

"Most published research findings are false" (not reproducible)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182327/

umvi2• 6 years ago

Reproducibility crisis is well known, especially in social sciences. However, it affects other science fields as well.

In a nutshell, the crisis is that there is far more incentive to churn out a new publication/study than reproduce an existing one. So we have tons of studies that are the only one of its kind that have not been reproduced. The crisis part comes in where attempts to reproduce the results of these studies fail which throws into question the legitimacy of the entire field's publications.

So you can imagine how putting your faith into covid-19 related studies (such as effects of hydroxychloroquine) that were rushed and results not reproduced independently can result in problems down the road.

Science is probably the best tool we have for determining truth. However, it takes a long time and a lot of effort to converge on the truth and people put far more faith than they ought to in the results of fresh publications that have results they like (or fear).

gonational3• 6 years ago

“reproducibility crisis” is a euphemism for “fake science”, which now, by the numbers, accounts for the majority of mainstream establishment science.

Prove me wrong.

fsh• 6 years ago

"Fake science" implies intent to mislead. The reproducibility crisis is usually attributed to selection bias due to only positive results getting published.

Alex39173• 6 years ago

Meh. It wouldn't surprise me if these trials are being run by the makers of Remdesivir or some other drug, and they're purposely killing folks to make their treatment look more effective. It's a pretty common tactic in the pharma industry for drug makers to do trials with enormous doses of their competitors products to make them look more dangerous by comparison, and given that this whole thing has turned into a multi-billion dollar cash grab I would assume that that's what's happening here unless proven otherwise.

It's the same thing with famatodine, where someone observed that folks taking it for heartburn have a lower risk of death. So rather than doing an RCT with giving folks 10mg orally (a normal dose), someone started doing an RCT with like 140mg injected.

Just thinking about it logically, why would you ever give someone a drug that ostensibly works by blocking viral replication when they've already had the virus for multiple weeks? It makes zero sense, which tells you there is something shady going on.

cm21876• 6 years ago

Particularly in the case of a 1950s drug that has been consumed by millions of people, and which as far as I know was available without prescription until covid. It’s like saying aspirin is dangerous. Sure. At a certain dosage.

mariodiana• 6 years ago

Exactly. And the dosage being given for COVID-19 patients is comparable to the dosage given for patients with chronic conditions such as lupus, only the COVID-19 patients are given the drug for something like a week, while the chronic patients are given the drug indefinitely.

Meanwhile, drugs like benzodiazepines are basically just dumped on a largely unwitting populace with the tacit blessing of these very same people who are fretting about hydroxychloroquine. There is more than simply the disinterested caution of science going on here.

bonzini• 6 years ago

Quinine-based drugs are no small thing. They are neurotoxic even at low dosages, for example (the somewhat-related antimalaric drug mefloquine very often causes really bad nightmares, at the very low prophylactic dosage, and it has a long half life so they persist even a few weeks after you've stopped taking it).

frenchyatwork3• 6 years ago

The risk of treating patients with pain-reducing levels of ASA (aspirin) is actually a significant issue, and it's not hard to find papers covering this issue, and reporting data on it. It's usually in older populations who are more likely to be in pain and also more likely to die from a stomach bleed.

halflings2• 6 years ago

Aspirin can be deadly if used to treat patients with an hemorrhage. Likewise, treating patients that are infected by a virus is not like preventing malaria in heathy people might to be exposed to a deadly virus like malaria, especially when most deaths are from older people which might be more sensitive to side effects.

zackees3• 6 years ago

This is not the only sabotaged study being done on HCQ.

As I pointed out on Twitter over a month ago, the bill gates foundation was doing a study on HCQ for preventing covid19.

The "inert" placebo they decided to use in the control group? VITAMIN C.

That's right, one of the most potent and documented immune boosters is now being assumed to be "inert".

https://depts.washington.edu/covid19pep/about/

dpoochieni6• 6 years ago

Fuck you are right, remember just reading that Gilead gave some 250K to the author of one of the studies against HCQ. IF that is not a conflict of interest then what is?

Alex39173• 6 years ago

Nice, if you can find the source I'd love to see that.

edit: I'm assuming this: https://www.thenewamerican.com/usnews/health-care/item/35547...

pjc50• 6 years ago

This is essentially the Andrew Wakefield fiasco on speedrun, isn't it?

My skepticism was founded entirely on seeing who was promoting this idea, and it is slowly being vindicated.

lbeltrame10• 6 years ago

My skepticism was founded entirely on seeing who was promoting this idea

The proponent has no effect on the null hypothesis. What was needed was a RCT: no results are out for any, at this point.

dougmwne• 6 years ago

I disagree from a statistical point of view. Of all possible hypothesis we choose to study, for the great majority we will fail to reject the null hypothesis. (For most things we study, we will find the treatment has no discernible effect.)

If some unstudied hypothesis is being promoted at random by vested interests, the chance that it is in fact an effective treatment is low because most treatments we would try are ineffective. And a vested interest will use every rhetorical tool at its disposal to promote what it is selling, including citing studies and scientists. If those do not exist or seem low-quality then skepticism is warranted. We should be wary of all medical claims till they are supported by high quality evidence.

take_a_breath• 6 years ago

If the snake oil salesman presents a new, improved brand of snake oil, skepticism is wise.

maxerickson• 6 years ago

You are describing a decision making framework with no real world applicability.

Like, how do we decide which things to study with RCTs? We ask experts...

flashyfaffe2• 6 years ago

This is what I appreciate in YC feed. You got far more better information gathered in one than the MSN article shared initially.

Luc• 6 years ago

For better information, I would suggest following the credentialed scientific experts on Twitter. You can get information straight from the very best people in their field.

Here, I feel it's a bit of a crap shoot, and half the comments are misinformed & happy to share it.

dpoochieni6• 6 years ago

Haha, damned Poe's law, hope this was sarcasm!

During Galileo's time most credentialed experts believed the sun to spin around the earth.

zabana• 6 years ago

Interestingly enough, the french military are still using it to treat their personnel.

fratajcz• 6 years ago

They have only confirmed ordering some in case it is proven to be useful. (this was 1 month ago)

https://factuel.afp.com/oui-larmee-francaise-sest-procure-de...

scottmsul• 6 years ago

A cardiotoxicity paper from the WHO in 2017 said the following:

"Despite hundreds of millions of doses administered in the treatment of malaria, there have been no reports of sudden unexplained death associated with quinine, chloroquine or amodiaquine, although each drug causes QT/QTcinterval prolongation. Unfortunately, there are relatively few prospective studies of the electrocardiographic effects of these drugs."

Link to paper: https://www.who.int/malaria/mpac/mpac-mar2017-erg-cardiotoxi...

Link to Chris Martenson's video where I first heard about the 2017 paper: https://www.youtube.com/watch?v=rN_YpFhdii4

Chris Martenson is doing an awesome job staying on top of the science in an apolitical manner.

Alex39173• 6 years ago

Having ACE2 receptors depleted increases blood pressure and changes the properties of blood itself (probably the source of the weird clotting issues), so it makes sense that there would be more risk with Covid-19. Plus many or most Covid patients are probably already polypharming with 5+ drugs already given their age, unlike people going on vacation to Bali or wherever.

I wouldn't trust the trials showing that it's dangerous, but I wouldn't assume it's safe either.

klmadfejno• 6 years ago

The data from those hundreds of millions of doses were on people who did not have COVID-19. It's not contradictory to say that the drug does not tend to cause these effects generally, but does cause these effects in a specific context. Like, say, a deadly disease wrecking havoc on your oxygen levels. Maybe it does, maybe it doesn't. Hard to know anything.

cozzyd• 6 years ago

Also, the dosage may be different

YeGoblynQueenne• 6 years ago

From the linked paper:

Summary of findings and proposed recommendations

1. Apart from halofantrine, antimalarial medicines thatprolong the QT/QTc interval,such as quinine, chloroquine, artesunate-amodiaquine and dihydroartemisinin-piperaquine,have beenassociated with a low risk of cardiotoxicity.

This seems to indicate that there is a risk, albeit low. The risk is for cardiotoxicity, not sudden deaths.

France, Italy, Belgium stop hydroxychloroquine use for Covid-19 on safety fears

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