From what I can gather chloroquine is already used as a first line treatment in Italian hospitals (at least it is indicated as such by the COVID treatment guidelines published by the society of Italian infectious disease specialists [0], and has been for quite some time - this document is from 10 days ago, but an earlier revision was not different regarding chloroquine). If this is the case, it's pretty clear that this is no miracle cure - it has at best a marginal effect.
[0] http://www.simit.org/medias/1569-covid19-vademecum-13-03-202...
Per some interview with some Chinese doctors who battled COVID19, they said that for many critical patients, their viral load is actually low, but the virus had caused damages to all parts of their bodies thus antiviral isn't going to do anything significant at that stage.
This might suggest chloroquine could be helpful at earlier stage of COVID19, to help prevent patients developing into server/critical stage, which would still be a very good thing if hold true.
I believe with the number of patients they have, they would've updated the guideline if it wasn't effective at all. But how effective it is we don't know. If a large percentage of some areas is already infected but the health system is still in the state it's in now, it could actually be a good sign. If the current numbers are realistic (which I don't believe at a positive test rate of >30%), it's probably not. We simply cannot know.
> Il trattamento deve essere accompagnato da trattamento antivirale (lopinavir/ritonavir o remdesivir + clorochina/idrossiclorochina) e/o steorideo (desametasone)
This is from the 13th of March so I guess there will be still some days until we see results of this (either positive or negative)
That seems like pretty strong evidence that the new treatment protocol is drastically decelerating the pandemic in Italy.
What are you basing "it has at best a marginal effect" on?
This is very wrong; we have good aggregate statistics across lots of different hospitals, but for a study with a small number of sites where the patients are treated with the drug, there's enough inter-site variability that may obscure any effect, or create a false effect.
This is doubly true as health care varies as sites get overwhelmed, and healthcare workers get increasingly strained from long shifts. There will be far more variability as time goes on.
And for how small we expect the effect to be, based on the data in the paper, we really should include controls.
All that said, I think that the publication of this flawed study is very good, and why pop-science takes that excoriate science as "most research finding are false" really communicate the wrong way to think about science, and limit its applicability. Flawed datasets like this still give us clues, and publishing flawed data is still useful to others to accelerate the pace of science. Which is why we need to take the attitude that publications are point in time guesses at what's going on, and only rarely does one come out that can be considered on its own as definitive, and that it's good to have mostly "here's some data and analysis but we don't have a complete theory yet"-type-papers. Without those intermediate publications, science would grind to a halt.
The simple solution is to spread it over enough sites so that the law of large numbers quantifies that variability into the dataset. For example if we run trials over 10 hospitals in 20 different states, 200 sites in the dataset would almost certainly capture inter-site variance.
There are a bunch of "contract research organizations" all over the world, quite a few of them making billions of dollars a year, who specialize only in running clinical trials because these things are so complicated. The documentation for clinical trials are often thousands of pages long describing tiny details like device calibration across hospitals trying to eliminate as many risks as possible. These organizations tend to have long standing relationships with hospitals and host many different trials in each one with a bunch more subcontractors who do patient selection.
> There is no new risk associated to using it that doctors arent already aware of.
You're imagining that their might be an unknown benefit using it with a novel disease, but you're confident that there won't be unknown risks?
Drugs just have effects. Risk/benefit is a human construction we apply over the top. There's no reason to expect only good surprises here.
Think about it like this: If these researchers had done a proper trial - and there's absolutely no reason to think that they couldn't have done that in the same amount of time with the same amount of effort - then we'd actually know something useful now. With that trial - we don't.
If we want to deal with covid we should have started years ago. As ever, we didn't.
There is EVERY reason to think they were not in a position to a "proper" test. They are in the middle of an epidemic!
So much for that given the president was recommending chloroquine to be used off the cuff.
I mean, you could say the same of practically any older drug. It's a fairly well-understood, cheap, somewhat dangerous drug.
> we do have a lot of statistics now on the outcome of patient not treated with that drug.
Sure. We also have a lot of statistics on the outcome of patients not treated with thalidomide, and morphine, and basically any other cheap somewhat dangerous drug you care to mention.
> if there's no suscipicion this drug could cause new problems
While I don't think there are, there's the certainty that it will cause the usual old problems that this drug causes. Which you probably don't want when you also have covid-19.
We'd be better off waiting on a proper trial.
> if there's no suscipicion this drug could cause new problems, we should have people massively use it
That's not how evidence-based medicine works. The drug is known to cause new problems because of the side effects. Clinical trials are needed to determine whether these are outweighed in patients by positive health effects.
You do not prescribe medicine on the basis of hunches.
What are you talking about? The severe side effects are known and are usually associated with chronic usage of that drug. Chloroquine is taken for prophylaxis against malaria (daily) in many places in the southern hemisphere. Usual regimen is at least for 8 continuous weeks!
EDIT: Toxicity here: as you can see it's very well tolerated. https://eyewiki.aao.org/Hydroxychloroquine_toxicity
What health authorities want to do is to allow physicians to use the drug if the patient agrees, but only in a controlled setting in which data is collected and there is a control group. So at least afterwards we could draw conclusions about whether it killed more people or helped saving people. Does that not make sense to you?
First is prophylaxis for front line health care workers, who are suffering grave infections likely exacerbated by long hours and low morale. Long term use of chloroquine or alternatives is a concern for this audience. There were fatalities last time, just like this time.
The second is for the patients themselves, who will otherwise endure uncontrolled viral replication for up to two weeks until the adaptive immune response recognizes the pathogen. Reducing transmission requires an earlier end to this stage.
Is the data from the previous studies worthless for these goals?
No. Likely needs to be given closer to onset of symptoms.
"The suggestion was to massively prescribe it."
No. The suggestion is to generate more evidence as fast as possible since it looks promising.
Cannot wait for full clinical trials. 1500+ deaths per day in the mean time.
Why are you fighting it so hard? If this is a useful treatment, don't you want us to find out? Let the doctors do their thing.
Doctors have the authority in many countries to prescribe it off label based on their own review of the evidence and their patient's consent. That's the best we can do right now without risking something much worse.
The goal here is to get enough evidence the treatment works or doesn't work. Conducting double blind studies is not the most efficient and fastest way to do that when you already have a lot of preexisting knowledge about both the patients not receiving any drugs and the safety profile of the drug in question.
This is again a situation where statisticians should be asked for help as medical professionals very often operate on very simplistic model (double blind or gtfo) which we just don't have time for this time around.
And yet trials for new medication against these diseases always include a control group.
It does, but why can't one can have the control groups at the same as blanket prescribtion? In times like this when the health care apparatus is overwhelmed, is it a good alternative to do that, since side effects are well-known and given the fact that the drug might be ineffective if used late in the infection cycle [0]?
And you just described the reason for a control group. We simply do not have that information. Things are moving too fast and treatments have not been standardized yet, not to mention the built in variability between locations. If you want to know if a treatment is effective, you must have to comparable groups. The point of the control group is to gather that information. Just because there are many, many, global cases doesn’t mean you actually have been able to capture the data for a control. Things are moving that fast.
> But if a doctor wants to prescribe all its patient with it, he should be allowed to
And what about the supply of these drugs? There are people who do need these drugs for other conditions (I’ve read Lupus patients sometimes need it). These patients need the drug and the supply is getting scooped up by people who don’t know (a) if they have the virus and (b) if the treatment is effective. And if it is effective, is it effective for treatment of infection or prophylactically? Just because a drug is widely used does not mean that there is enough supply to distribute it to anyone who wants to try it.
These are major issues that can be answered with proper clinical trials. We know how to do this and they can (and are) being done as fast as possible.
I’d suggest we need to get it to people before they end up in the hospital to try to keep the resources available.
See https://www.drugs.com/sfx/hydroxychloroquine-side-effects.ht...
If the discourse become authoritative and biased, we shut it, disregard it pointing out the flaws. But we have to be careful not to be authoritative ourselves when we don't even give the chance for the writer to be wrong because he lacks the right credentials.
Basically, I've seen my share of unqualified people (not that I'm qualified myself) building ridiculous models of exponential growth and predicting catastrophes, commenting on drug research protocols without necessarily understanding the details and so on.
Nor on the basis of panic; we should be able to manage this pandemic as long as people stick to the measures in place. Stay at home, limit your shopping, don't take the piss. I mean panic right now is causing more problems - e.g. hoarding and people trying to make a quick buck.
This thing is mainly a big problem because people can't keep calm and rational. Or they think they're rational, as in, "I should buy enough toilet paper because I should stay indoors for a while".
These are very real concerns for which no one has answers. People are stockpiling because of the uncertainty, which could be seen as a very rational stance in hindsight if this goes on for quite some time.
To clarify, hydroxychloroquine has far fewer side effects than chloroquine.
Hydroxycholoquine is very safe and is prescribed to lupus patients daily. The Korean recommended dose (400mg/day) is the same as what is prescribed to lupus patients. Chloroquine is a bit more dangerous, but only in high doses and over long periods of time. Patients would be on either for 10-20 days maximum which is much less than what it takes to be dangerous.
Both are less toxic than Tylenol.
The drug is 90 years old, has been used by millions, has relatively modest side effects, is relatively well-understood, has shown efficacy against coronavirus in vitro.
And it's not just for drugs. It's also why DDT continues used in some countries but is illegal in others.
I would only want this drug given to me if there was no hope of recovery.
Advil has probably killed more people than hydroxychloroquine.
What should not happen now is, that the general public starts taking the drug as a precaution, just because it might work. The known side-effects are too severe (e.g. blindness) and also, there are already shortages of the drug for those who already require it as part of their medical treatment (e.g. immune-supressed).
This side effect occurs if you take chloroquine for extended periods of time. Look at the data.
https://eyewiki.aao.org/Hydroxychloroquine_toxicity
"Risk for toxicity is less with <5.0 mg/kg real weight/day for hydroxychloroquine and <2.3 mg/kg real weight/day for chloroquine[2]. Patients are at low risk during the first 5 years of treatment."
And management is as simple as stopping the drug if it starts affecting your vision:
"At the first signs of retinal toxicity, hydroxychloroquine should be stopped to prevent further retinal damage and visual loss[2]. "
Common (1-10%): rash, itching, diarrhea, vomiting, loss of appetite, headache, blurred vision, "Affect liability" (got no idea what that is).
Most SLE/Lupus patients take HCQ, and reportedly none in the cohort of the doctor I know have sufficiently severe symptoms to qualify for pCR testing to even establish if they have Covid19. This is Spain with (currently) 708 cases per MM. Of course, caveats like absence of evidence is not (necessarily sufficient) evidence of absence. It may be that SLE or other immuno-modulation treatments have some effect - someone should do analysis with matched non-SLE HCQ and non-HCQ prophylaxis cohorts. But back to my main point with the house burning metaphor for exponential infection - the risk landscape demands we take more risk, give HCQ widely instead of waiting for the conclusion of prospective studies. We can withdraw it if it is shown to be no better than placebo or worsens outcomes when enough data is available to conclude.
3) Again this drug has well known precautions that reads like the all the people who will experience the worst of COVID-19
Having Grandpa John walk in for COVID-19 and roll out for death by QT elongation is not something the public will have to litigate.
Except those precautions are at least two orders of magnitude less than the case fatality rate for coronavirus infection.
Equivalently, there are scenarios where a seatbelt can decapitate you or trap you in a drowning car. But you'd still be a fool to drive without one, because buckling is a thousand times more likely to save you than kill you.
The most serious cases of COVID-19 affect all the people who have the underlying conditions that have precautions listed using H-Chloroquine.
That makes the normal ICU case of COVID-19 more difficult (time consuming) to manage because now you have to spend time managing / monitoring: The condition, COVID-19, the side effects of H-Chloroquine on vital body systems already impaired, already being attacked by COVID.
Throw the magnitude two out the window like a lucky car crash victim while these patients suffer the crash in the hospital. Not even Bernie was going to pay for the specialty concierge care needed to manage such a patient and yet you some how assume that is how it works.
Has side effects in patients with G6PD deficiency (10-15% in some populations)
Cardiotoxicity, retinopathy, and these are especially likely in older patients.
https://www.bloomberg.com/news/articles/2020-03-20/virus-dru...
Disclaimer: am not a MD or public health person, but I talk to both.
This is very difficult to do. In this study all the patients in the treatment group are from a hospital and most of the patients in the other hospital are from other hospital. Do the population of both hospitals have the same median income? Usually a low income cause a bad diet that may cause bad health that has a worse prognosis.
Are the patients in the other countries classified by income? Does the difference in income cause more/less consumption of milk? Bottled milk has an additional amount of vitamin D, and some unconfirmed reports say that the lack of vitamin D is bad for covid19. Does this difference depend on the country? For historical/genetic reason, French drink more milk that Chinese. What about wine, is the consumption of wine important?
What is the effect of temperature and humidity in the no-hydroxychloroquine group? The average climate conditions change from country to country and from place to place and from month to month.
To be included in the testing group the patient must give consent. Probably they have not to be too wasted to be able to read it. Probably not been to wasted is a good sign.
There are a lot of factors, and not all of them are known, not all of them are easy to measure, not all of them are measured. So you need a control group.
The point of these studies is to help the evidence catch up to improvised clinical practice. If the studies are poorly designed, that goal is not achieved
Prayer? Meditation? Garlic? Red wine? Cannabis?
...I mean it is a big loophole. Something I've wondered about for years is V-8 juice. Seems healthy, but what about the psoralens in celery?
I'm not saying that everything does need to be tested, but if you don't, you don't really know and no mental gymnastics can change that.
You can't possibly know whether this drug would have adverse interactions with a new illness.
This is not some crazy experimental new drug that was unknown until past week. It's an experimental treatment, it's not an experimental drug, with unknown side effects. For a condition where time is critical.
Of course, we should also be quick to discard unpromising drugs, and not only focus on one promising drug.
WHO is starting a megratrial of several drugs now https://www.sciencemag.org/news/2020/03/who-launches-global-... (including CQ/HCQ)
If it turns out to shorten the illness, everyone sick, and also everyone taking it prophylactically who is actually infected but asymptomatic, will reduce their contagion rate by joining the ranks of the non-contagious sooner, reducing everyone's risk. If it does not turn out to shorten the illness, no harm done.
Chloroquine is well-known. If it caused an unacceptable rate of liver failure we would already know.
I see suggestions that it takes a very high doses to work. But that might be so only for the already severe infections they are using it on. It should be easy enough to discover whether low doses work prophylactically, and safe enough to try them while waiting on results.
Coughing your lungs out but feel like CNN is not lying to you? Easy! Refuse the drug. Nobody can force you to take it.
Worst thing that can happen with a chloroquine and azithromycin combination is that it causes heart arrhythmia and sudden death in a patient that would not have otherwise died.
Studies of patients taking this combination of meds include daily EKGs, which is something the general population at home isn't going to have access to.
https://twitter.com/search?q=azithromycin%20qt&src=typed_que...
I bet it can, if FDA is beat over the head with a shovel, which it will be if the need arises. It's a real ECG verifiably capable of detecting irregular hearth rhythm, and it costs a tiny fraction of what a big-ass ECG machine would, and therefore can be deployed at a much larger scale. Just because it could only get approval to detect atrial fibrillation duing "peacetime" doesn't mean it can't be pressed into service for other things.
1/ chloroquine is a very well known cheap drug. There is no new risk associated to using it that doctors arent already aware of.
2/ we do have a lot of statistics now on the outcome of patient not treated with that drug. There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare.
3/ people are oversaturating ICU right now. And as such, it is an emergency situation. We should take the reverse reasoning we usually take : if there's no suscipicion this drug could cause new problems, we should have people massively use it whenever possible and look at the result after 6 days (since that's the time the original study says it takes for the first results to show).