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.
 https://statmodeling.stat.columbia.edu/2020/05/25/hydroxychl... and related posts
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.
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.
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.
On currently-available evidence, the balance of risks is to not prescribe this drug for treatment of C19.
This is the worst case in terms of risk trade-offs:
Without being admitted as a patient, you will not be monitored as closely especially for coronary complications.
Since you'll be giving it to people before the onset of severe symptoms, you'll be risking side-effects giving it to people who might have been fine without it (and most people will survive with out it).
You'll be giving it to a lot of people which again just increases the chances of serious side-effects.
(PS I hope you're doing well now).
It is a basic and important medicine. It's not that there are no concerns about its safety; it's that the safety concerns are well-known. Those are distinctly different statements.
(As an aside, for example, Tylenol and aspirin can both be quite harmful, but under what conditions they're dangerous is well-known so they are widely used pretty safely. Even so, you still find people inadvertently destroying their livers with Tylenol/paracetemol when they don't realize two OTC medicines contain them and overdose).
So then the question is how much harm are you doing by giving people the drug (under some set of circumstances) vs how great a benefit might someone derive from it.
Clearly on one side, if you gave it to everyone as a prophylactic, that'd likely cause more harm than good. Perhaps, you give it to people who have tested positive but are not admitted to the hospital. Or you can give it to only those who are admitted. Or you can give it only to people who are doing poorly.
Presuming the harmfulness of the medicine is well known you can run some easy hypothetical numbers about how many people will have serious harm or death from receiving it on a wide scale. We have a rough idea of the range of people who will die or have serious cases of COVID. The only thing left is the possible benefit people may get from the medicine.
As of now there is no indication that the benefit is worth the harm to give it out to people in a wide-scale fashion. Additionally, the current studies don't even support giving it to people who are in-patients. In most studies, patients receiving it fare worse than those not.
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.
"No serious cardiac adverse effects were recorded in malaria clinical trials of 35,548 participants who received quinoline and structurally related antimalarials with close follow-up including 18,436 individuals who
underwent ECG evaluation."
"Chloroquine is the most widely used antimalarial drug
in history. It has a terminal elimination half-life of
one month and an annual consumption of hundreds of
tonnes for over 50 years, so it may be the drug to which
humans have been exposed to most. Despite producing consistent QT prolongation, the only case reports
of TdP and sudden death have been for its use for
non-malaria indications such as systemic lupus erythematosus or rheumatoid arthritis, where high doses are
used for much longer than in malaria treatment, or in
They are often conflated in the media and colloquial reporting.
Anyone can verify what I'm saying if they go to scholar.google.com
Lastly, the argument of "if countries outside the US are prescribing it, it must work" is just nonsensical. Doctors prescribing a drug is not evidence a drug works.
Sciencemag  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.
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.
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).
This is the same for remedisivir, and also for ritonavir/lopinavir/ribavirin: they must be given within 7 days of symptom onset to be effective. In fact, the latter was deemed unsuccesful in a first paper, because it was given late, then it was reconsidered when given earlier during the disease.
This is not surprising, given how the disease works (outlined also by the Cell paper from yesterday): at some point the consequences of the highly altered inflammatory reaction greatly surpass the effects of the replication of the virus itself.
This calls more for extensive and early testing, IMO.
participants who entered the trial more than 10 days after the onset of symptoms actually showed a better response to remdesivir than those who started being treated during the first 10 days of being symptomatic.
It's not a huge improvement, but it doesn't seem to be too dependent on starting treatment early.
HCQ's issue may be a bad combination of "has to be taken early" and "has significant side effects".
Not in an antiviral context, and certainly not for SARS-CoV-2.
As has been mentioned elsewhere, we'll have to answer soon, but power speaks with a forked tongue in this case. Too many anecdotal observations to be comfortable in the very loud politicization of the science.
The Lancet study and others cannot be accepted a conclusion to the safety & efficacy of early/prophylactic use. Let's wait for and encourage some proper, specific studies.
Yes, which is why all of the studies keep saying that it's too dangerous to use as treatment for covid-19.
It may be too toxic, it may not cause a noticeable effect, but currently it is a big question mark.
 Except now we know (and we always thought this) that it won't save their life; it'll increase their risk of death.
To be fair, Didier Raoult has changed his own claims several times (including dosage, drug mix and he even switched from chloroquine to hydroxychloroquine – afait, these are different molecules). Including after the studies were started.
This doesn't mean that he's wrong, but at this stage, there are so many red flags that it's hard to take anything he said seriously.
Research scientists have all the time in the world, clinicians don't. Once again, it's a peacetime army of bureaucrats vs. an unknown enemy that doesn't have the decency to wait for understanding to catch up with reality. Decisions have to be made with an imperfect understanding, in a reality that changes every day.
The truth will seem obvious afterwards, but right now it doesn't. Those not on the front lines should keep to their very important job of improving prospects for the future, and keep the judgement out of it.
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)
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.
FTR, the U of Minnesota trials used normal dosages and (according to its PI) did not report any cardiotoxicity so far.
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.
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.
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).
Randomised Controlled Trials are the gold standard but not the "most basic thing". They are the ideal we'd like to have but often simply aren't an option.
One of the most obvious reasons we often can't do a trial is that we have good reason to believe it would be unreasonably dangerous, which is why these trials stopped.
The opposite scenario happens sometimes too. If all patients treated with Hydroxychloroquine magically got better they'd stop the trial and recommend immediately using it on similar patients.
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).
Prove me wrong.
By calling it "fake science" you're touching on the idea of a paradigm shift, that periodically the community changes its beliefs about what enables someone to know something or to be certain about something.
To illustrate, the literature that you’re describing is presumably in the form of meta-analyses published in Nature. How can we even trust that to be “reproducible” (aka correct)?
I think the correct reaction to this situation is to completely stop trusting scientists and their papers, in general. Not trusting scientists add their papers doesn’t mean disbelieving science in general; it just means the established institutions do not know how to do science correctly, and I believe this has been the case since the beginning of modern science. That means we can learn things by reading between the lines and using some common sense, but we can’t simply rely on institutions to tell us the correct answer to anything whatsoever.
Incorrect. It's in the form of math. Deductive, not inductive.
> completely stop trusting scientists and their papers ... since the beginning of modern science
You are using a computer right now. You don't trust it? Now you're just trolling me.
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.
edit: I'm assuming this: https://www.thenewamerican.com/usnews/health-care/item/35547...
The thing is it's pretty evident it works and also why many governments and leaders around the world are taking it as prophylaxes. Anecdotally (doctors in the family), it is being used in private hospitals in my country quite successfully.
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.
Doctors in the heat of the moment cannot wait for a randomized trial. They started keeping patients off intrusive ventilators without doing a randomized trial, based on annecdotal evidence.
But these trials still need to happen.
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".
"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.
I wouldn't trust the trials showing that it's dangerous, but I wouldn't assume it's safe either.
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.
My skepticism was founded entirely on seeing who was promoting this idea, and it is slowly being vindicated.
The proponent has no effect on the null hypothesis. What was needed was a RCT: no results are out for any, at this point.
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.
Like, how do we decide which things to study with RCTs? We ask experts...
Here, I feel it's a bit of a crap shoot, and half the comments are misinformed & happy to share it.
During Galileo's time most credentialed experts believed the sun to spin around the earth.