More on chloroquine/azithromycin and on Dr. Raoult | Hacker News Reader

More on chloroquine/azithromycin and on Dr. Raoult

blogs.sciencemag.org

45 pointshprotagonist18 comments

In those troubled times, a lot of people are just critisizing instead of doing something useful. There is a bibliography studying the effects of chloroquine and derivates to fight viruses. As scientists, the base of our work is to read papers and search for bibliography. Targeting people with ad hominem attacks is plain lame. Do some science FFS, and act swiftly in times of war.

https://www.sciencedirect.com/science/article/pii/S092485792...

https://aac.asm.org/content/53/8/3416

https://www.sciencedirect.com/science/article/pii/S0006291X0...

https://link.springer.com/article/10.1186/1743-422X-2-69

https://www.sciencedirect.com/science/article/pii/S016635420...

https://www.sciencedirect.com/science/article/pii/S147330990...

https://www.sciencedirect.com/science/article/pii/S016635421...

https://www.thelancet.com/journals/laninf/article/PIIS1473-3...

https://link.springer.com/article/10.1007/s00535-009-0132-9

https://link.springer.com/article/10.1186/1743-422X-3-39

That Didier Raoult appears to have a history of image manipulation is not an ad hominem, and is apparently true. His 2006 offense was sufficiently bad as to be banned from publication for a time in a leading journal in his field. That is also not an ad hominem.

You also completely fail to engage with the first 2/3 of the text, which has any number of impersonal methodological critiques which are not addressed through a literature search.

You point the exact problem here.

As a scientist the first test is intuition. The second test is having people getting better with treatment. The third test is conducting a full, deep study with the utmost scientific rigor.

So now there is a dilemna. People die in front of you. You try something. It seems to work. It uses a widely-used set of molecules (Hydroxychloroquine + azythromycine (+Zinc in some protocols). Will you try it, or will you make a double-blind study with half the people at risk of dying ?

History of aviation. People just couldn't believe that it was possible.

http://www.wright-brothers.org/History_Wing/Aviations_Attic/...

"Not wishing to be miserly with his information, Root sent an eye-witness account of what the Wrights were doing to the Scientific American, with a letter telling the editor he was free to use it. But the editor was not to be taken in and made no effort to investigate what Root had dropped into his lap. Though the Scientific American printed in 1905 many articles about flying, nearly all were about devices that maybe ought to be tried."

I don't fail in anything, I just don't need to engage in endless debates about methodology. Half of the studies in psychology fail to replicate. There are problems everywhere in science, because geniuses are still rare and now ostracized because they produce new researched and are judged by lords of the old order. If you scratch hard, you can always find something.

Some people criticize, others just act. The people who create are always going to be the targets of the people who spend their time criticizing.

Now it's time to act. Not pull over waiting for some authority to decide for yourself. The list of publications is here to show that this available treatment doesn't come from a magical hat.

you’re good at grandstanding, but you have yet to meaningfully engage with the numerous methodological critiques of Raoult’s work which, if unaddressed, make his result unethical and inappropriate for use as approval to act. There have been blinded trials of chloroquine; they have their issues too, but didn’t show an effect.

the side effects of chloroquine are nontrivial, at least one person has died in an attempt at self-medication by ingesting a substance that had a similar looking word in it, and pre-existing patients who do need the drug are being deprived of it as hucksters run rampant.

Keeping an even keel in a crisis and knowing when to make informed decisions on limited data and when not to are skills we develop and must have the strength to use as practicing scientists. Especially when it feels tempting not to.

Give me a break...twice. The guy who ingested fish tank cleaner was a tried and true moron. And when you have a crisis of this extent you do what you have to do and relax the, ah, formalisms a little.

"Relaxing the formalisms" is great!

"Tolerating scientific fraud" is not. This doctor has previously come very close to scientific fraud. That means that for us to trust him again, his work needs to be impeccable. It isn't.

This potential treatment is promising enough that it is worthy of study, and in lieu of better solutions, administering to patients. These are drugs that have a known safety record for human use. But if you stop and think this is any form of "cure", you are deceiving yourself and endangering lives. It's pretty clear that chloroquine/azithromycin probably doesn't make COVID-19 any worse (in general). But it's not clear yet that it's actually a good treatment, and if we stop the search now, that is to our own detriment.

- the couple who ingested fish tank cleaner were, first and foremost, people.

- when you have a crisis like this, doing what you have to do involves doing things as clearly as possible to extract the most information you can from limited data and report it honestly and completely. That is not what's happened here.

> As a scientist the first test is intuition.

I have been wrong so many times. Moreover, I'm very good to point the right idea but like 50% of the times I get the conclusion in the wrong direction. Luckily my coworkers take a look. (And none of the decisions involve human or animal lives.)

> The second test is having people getting better with treatment.

The dead rate is something between 0.2% and 20%. It depends on your age, your health, and how wide is the test network. It's a 100 fold (and perhaps more). So whatever you do, most of the patients will get better. And without a baseline it is very difficult to compare.

For example, they ask the people if they want to participate. This is a filter that exclude the people that is very ill. What is the death rate in the subgroup of persons that are capable of signing a form?

> You try something. It seems to work.

How are you sure that it is working if you don't have data to compare? The "control group" was in another hospital. Does the patients in the other hospital have the same median income level? (Being poor is corelated to a lot of health problems.) Can all the patients in the other hospital sign a form? Is the other hospital nearby a university and it get a lot of young patients or it is nearby a geriatric and it get a lot of old patients?

> Now it's time to act. Not pull over waiting for some authority to decide for yourself.

But we don't know if this treatment is good or bad. Someone posted a link in another thread to a list of 20 home remedies and supplements that may be helpful. Which one should we apply? Can we use all of them together? Which are the side effects? They are not very well tested, so some of them may be harmful.

Note that in this study, one of the persons treated with the combination of drugs died, but none in the "control group" died. What is the conclusion? Is this combination of drugs safe? (Note: This is clearly a fluke.)

> The list of publications is here to show that this available treatment doesn't come from a magical hat.

Cross out the first study because it is not reliable. Try to read the second one more carefully, perhaps it has some surprises.

Yes, but the author makes more efforts describing him as just bad person then as lousy scientist which is certainly ad hominem.

Thanks for your posting. I am curious how many of the links you posted were chloroquinine (or HC) in vitro only, versus in vivo on mice - - versus in vivo on human subjects ?

Hello, and thank you ! Exploring the dependency graph of this paper is a good starter [0]

[0] https://www.nature.com/articles/s41421-020-0156-0

Yes, you start with molecular studies, then in-vitro, then in-vivo, then in humans, and in the end, sometimes it gives good results, sometimes not.

> As scientists, the base of our work is to read papers and search for bibliography.

A huge part is distinguishing good articles from bad articles. Do you think all peer review articles are correct? In which field do you work?

Let's analyze the first article you linked. It's the previous article about this topic of Raoult, not an independent research. Did you notice that he control group is not randomized, and most of it was in others hospitals, so it's not clear that they have the same treatment and same prognosis.

Also they are not counting the 6 patients that they lost in the treatment group (1 just leave, 1 had too much nausea, 3 where transfer to ICU, 1 died).

It is more strange that they didn't lost any patient in the control group. (Someone gave an answer to this in a previous thread. Can you spot it in the paper? Do you think after this that calling the other bunch of people a "control group" is accurate?)

> Now, it would be a more simple world if assholes were always wrong about things, and I am not yet prepared to say that Dr. Raoult is wrong about hydroxychloroquine and azithromycin. But neither does he seem to be the sort of person who is always a reliable source, either. I do not take pleasure in this. But I am less hopeful about this work than I was when I first read about it, and I can only wonder what direction those hopes will take in the weeks to come.

In weeks to come there'll be people living and people dying. I'm not sure in which group I'll be. But all discussions about the Dr. Raoult personality doesn't add up to the big question: does it work or not ?

we don't know; the data that personality generated isn't helpful!

See here: https://sciencebasedmedicine.org/hydroxychloroquine-and-azit...

the results are so uninterpretable as to not help the SNR on the issue.

With all the known cases (e.g. 100k in the US) and about 0.5-1% taking HCQ continuously already for lupus and other diseases, if these people are underrepresented, we have a big clue that it works, almost to the point of proof (need to show that it's not the underlying condition that stops the virus, a-la sickle cell anemia vs malaria). If they are equally represented, it's discouraging, but not proof that it doesn't work (again because of underlying being a confounder).

This information should readily be available to the CDC or whoever else is tracking the cases. What am I missing? Why do you have to wait for double-blind trials?

hipaa, nonstandard data recording systems, time, confounds of preexisting medical conditions, scattershot testing, and the overall saturation of the healthcare system are going to make that signal more or less invisible.

We are talking about the confirmed positive cases, these people are all potential spreaders and are supposed to be closely monitored. This is a standard CDC playbook (lots of people I’ll, find out what’s common to them). The list you gave, if true, is total incompetence of e CDC to a level which has never been demonstrated before - in fact, the CDC has generally done well with their playbook even if it was a couple of weeks late (and we’re 10 weeks since I heard from a friend who works with the CDC that they’re watching it)

More likely to work early on in the infection, I doubt any anti-viral would be very effective once the patient experiences ARDS.

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