11 ms·

I see many problems with all the caution around that study: 1/ chloroquine is a very well known cheap drug. There is no new risk associated to using it that do

by bsaul 7y ago

I see many problems with all the caution around that study: 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).

ncmncm 7y ago
In particular, if it turns out to reduce infection rate, taking it prophylactically will save the lives of everyone who would otherwise die for lack of a ventilator, or who would die even with one. If it does not turn out to reduce infection rate, no harm done. 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.
- joe_fishfish 7y ago
  What if it turns out to shorten the illness in 80% of cases but cause liver failure in the other 20%?
  - learc83 7y ago
    It's a well known drug. We already know the side effects.
    - kl4m 7y ago
      Not on people with COVID-19.
  - tyingq 7y ago
    Hydroxychloroquine is significantly less hepatoxic than chloroquine.
henriquez 7y ago
Exactly. Since the risks and side-effects are well-established, it’s more ethical at this point to experiment on humans with an “off label” usage. Doctors do that all the time with other meds.
- _ph_ 7y ago
  Yes, doctors should experiment with the drug and I am certain, a lot of those, who have the necessary conditions to perform a proper experiment, will do. 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).
  - ekianjo 7y ago
    > Blindness This side effect occurs if you take chloroquine for extended periods of time. Look at the data. https://eyewiki.aao.org/Hydroxychloroquine_toxicity 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]. "
    - kevingadd 7y ago
      I'd note that the phrase "further retinal damage and visual loss" implies that retinal damage and visual loss has already occurred... how much of that you are willing to tolerate is up to you, I suppose: I'd prefer 0 unless necessary. If the retinal damage is saving me from a death at the hands of COVID-19 maybe it's worth it, but if it's not...
      - ekianjo 7y ago
raverbashing 7y ago
I have similar thoughts 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-megatrial-four-most-promising-coronavirus-treatments https://www.sciencemag.org/news/2020/03/who-launches-global-... (including CQ/HCQ)
jonathanstrange 7y ago
This is irresponsible. This drug has severe side effects, it makes absolutely no sense to prescribe it for a completely different disease without first confirming in clinical trials that it has positive effects. > 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.
- _red 7y ago
  You are currently running another experiment called: Crash the global economy. That's also irresponsible. Should 10-yr olds be forced to give their life to save 85 yr olds?
  - JoeAltmaier 7y ago
    Maybe a bit of strawman there. With more information (hopefully coming) we should be able to make more nuanced decisions.
- ekianjo 7y ago
  > This is irresponsible. This drug has severe side effects 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 https://eyewiki.aao.org/Hydroxychloroquine_toxicity
  - jonathanstrange 7y ago
    The suggestion on the table is to give this drug to extremely ill patients who suffer from a new viral disease on the basis of anecdotal evidence and without clinical trials. The suggestion was to massively prescribe it. 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?
hannob 7y ago
Opinions like this seem to be popular these days, but they're dangerous. Because this is an emergency we want reliable information. 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.
- throwaway_pdp09 7y ago
  Agreed, this kind of thinking comes from fear and desperation (and another kind is denial of reality - this can't be happening so it isn't. My neighbours still don't realise it's actually happening). If we want to deal with covid we should have started years ago. As ever, we didn't.
- hanniabu 7y ago
  > Because this is an emergency we want reliable information. So much for that given the president was recommending chloroquine to be used off the cuff.
- pbreit 7y ago
  "no reason to think that they couldn't have done that in the same amount of time with the same amount of effort" There is EVERY reason to think they were not in a position to a "proper" test. They are in the middle of an epidemic!
- ping_pong 7y ago
  They are in a war zone in Italy and presumably in the US very soon. If hydroxychloroquine is safe (except for some people with a known predisposed genetic condition), then we should be giving it widely and early. We can worry about the science and studies later on, but right now we need to save lives and decrease ICU overload.
- tim333 7y ago
  This was done in about a week. Where's an example of a clinical trial to your liking done that quickly?
httpsterio 7y ago
Being sick with a disease like Covid-19 could absolutely alter how a medication works on a person. The drug might be safe to a person with a certain profile and it has been tested against those, but each underlying issue is a new profile which it should be tested against as separately as possible.
- guiriduro 7y ago
  I think this is the fairest counter-argument I've heard so far about safety of HCQ in Covid-19. I still think the background of "you're in a house burning down, some tests tentatively indicate this may be effective..." weigh more against the risk of side-effects or worse progression due to CQ/HCQ. We ought to be able to devise some experiments to add certainty, using mainly retrospective data now available. 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.
- dcolkitt 7y ago
  Based on that reasoning, we shouldn't give any pharmaceuticals to coronavirus patients. Even simple fever relievers, like acetaminophen, or oral rehydration fluids should be prohibited because we just don't have enough data to know how they'll interact with COVID-19 specifically.
lultimouomo 7y ago
> 3/ people are oversaturating ICU right now. And as such, it is an emergency situation. 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.pdf http://www.simit.org/medias/1569-covid19-vademecum-13-03-202...
- raverbashing 7y ago
  Thanks for this reference, it seems they are proposing 2 potential treatments (p. 13) for the more severe patients > 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)
  - dcolkitt 7y ago
    For the record since that decision day, the growth rate in the number of deaths in Italy has fallen in half[1]. In the 9 days from March 13 to March 22 the daily number of deaths grew 160% from 250 to 651. Prior to that, the same level of growth occurred in 4 days between March 9 (96 deaths) to March 13. That seems like pretty strong evidence that the new treatment protocol is drastically decelerating the pandemic in Italy. [1]https://www.worldometers.info/coronavirus/country/italy/ https://www.worldometers.info/coronavirus/country/italy/
    - lultimouomo 7y ago
      This does not make much sense to me. If it was effective, it should decrease the lethality rate, not the growth in the number of deaths which is much more affected by the actual number of cases. In the page you link you can see that lethality rate has not fallen. Also, as I wrote I'm pretty sure that I saw an earlier version of that document, dating IIRC to the beginning of the month, that prescribed more or less the same combination of chloroquine and antivirals as a first line treatment.
jpz 7y ago
It isn't vitamin C. It has a lot of side effects, including serious psychiatric ones in limited cases. If you give it to 100 people you're going to get new health issues that you didn't have before in that population.
- jansan 7y ago
  Interestingly there is a trial to use a high dose of vitamin C to treat COVID-19 ARDS: https://youtu.be/bt-BzEve46Y?t=2107 https://youtu.be/bt-BzEve46Y?t=2107
kingkawn 7y ago
You cannot pour a drug into the populace that will cause side effects on a mass scale that might also overwhelm the healthcare system. It is nice to imagine we have the medicine already, that we can simply wave our hands distribute the pills and everything can go on as it was before this. But we do not and can not go back.
wpietri 7y ago
This is absurd: > 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.
- tim333 7y ago
  Though why should it have weird side effects when used for COVID that it didn't when used for malaria?
  - wpietri 7y ago
    As I said, drugs just have effects. Humans then look at the results, decide which are good and bad, and then label the bad ones "side effect". So I think the real question is: why do you think 100% of the novel effects will be later put in the "good" bucket?
m0zg 7y ago
Yeah, it's important to have it available if it's needed and it's important to conduct at least some sort of trial. Because the drug, combined with azithromycin is so fast acting, we should see the first results in a few days. Worst thing that can happen is it doesn't work. Best thing that can happen is we can save 1.8 trillion dollars and restart the economy. Under these circumstances one would be an idiot not to give it a try. Coughing your lungs out but feel like CNN is not lying to you? Easy! Refuse the drug. Nobody can force you to take it.
- DanBC 7y ago
  > Worst thing that can happen is it doesn't work. 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_query https://twitter.com/search?q=azithromycin%20qt&src=typed_que...
  - m0zg 7y ago
    That's why they are starting with a trial, and not a full scale roll out. Other countries are using this combination of drug, and it's not because they're huge fans of Trump, I can assure you. We also have literally millions of devices out there capable of detecting arrhythmia - they're called Apple Watch.
    - snegu 7y ago
      Apple Watch can't detect long QT, which is one of the risk factors here.
      - m0zg 7y ago
        That's like saying construction N95 masks can't be used in the medical setting just because they lack appropriate certification. That old shibboleth has been defenestrated weeks ago. 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.
gus_massa 7y ago
> There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare. 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.
rsynnott 7y ago
> chloroquine is a very well known cheap drug. There is no new risk associated to using it that doctors arent already aware of. 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.
- TheHypnotist 7y ago
  We know the side effects for a healthy individual or those with malaria, but how do we know for certain this won't cause new problems in those with COVID-19?
mrfusion 7y ago
You’re absolutely right. We need to act fast.
jcrubino 7y ago
2) It complicates the treatment of the patients who will experience the worst cases of COVID-19 causing panic... people above 65 with diabetes and heart conditions. 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.
- dcolkitt 7y ago
  > Again this drug has well known precautions that reads like the all the people who will experience the worst of COVID-19 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.
  - jcrubino 7y ago
    You missed the point. 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.
epistasis 7y ago
> 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. 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.
- dcolkitt 7y ago
  > 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. 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.
  - akiselev 7y ago
    That only normalizes natural variances in your patients, not artificial biases introduced by the healthcare system. Pump and other hardware measuring out dosages might come from different manufacturers or be calibrated and serviced by different technicians. Maybe the study includes one too many hospitals in a region dominated by one manufacturer whose hardware tends to error more in one direction than other manufacturers. The generics used by pharmacies and hospitals might be slightly different because of local relationships. Exercise, ability to have visitation in quarantine, and other amenities in hospitals will have differing impacts on confounding factors like exercise and morale. And on and on. 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.
herf 7y ago
Check PDR before you say things like this: https://www.pdr.net/drug-summary/Plaquenil-hydroxychloroquine-sulfate-1911.7193 https://www.pdr.net/drug-summary/Plaquenil-hydroxychloroquin... 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-drug-touted-by-trump-musk-can-kill-with-just-two-grams 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.
aaavl2821 7y ago
Many doctors are already actively prescrbign this. I heard that it is basically de facto standard of care in France. Doctors recognize that when eveidence based medicine doesn't provide an adequate treatment, they need to improvise. Off-label prescribing is very common 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
eagsalazar2 7y ago
I imagine some country/region out there will adopt this approach so we'll all get to find out in a few weeks (possibly at their expense).
- jansan 7y ago
  It is being used in several countries already (US and Europe, not sure about Asia). If you are interested in details, here is a video of a conference call at UCSF: https://youtu.be/bt-BzEve46Y?t=3194 https://youtu.be/bt-BzEve46Y?t=3194
IAmEveryone 7y ago
Your second and third point are completely independent of the substance at issue. So by that logic, we should test everything that is “safe”. Prayer? Meditation? Garlic? Red wine? Cannabis?
- perl4ever 7y ago
  https://en.wikipedia.org/wiki/Generally_recognized_as_safe https://en.wikipedia.org/wiki/Generally_recognized_as_safe ...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.
naasking 7y ago
> There is no new risk associated to using it that doctors arent already aware of. You can't possibly know whether this drug would have adverse interactions with a new illness.

by bsaul 7y ago

ncmncm 7y ago

In particular, if it turns out to reduce infection rate, taking it prophylactically will save the lives of everyone who would otherwise die for lack of a ventilator, or who would die even with one. If it does not turn out to reduce infection rate, no harm done. 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.

joe_fishfish 7y ago
What if it turns out to shorten the illness in 80% of cases but cause liver failure in the other 20%?
- learc83 7y ago
  It's a well known drug. We already know the side effects.
  - kl4m 7y ago
    Not on people with COVID-19.
- tyingq 7y ago
  Hydroxychloroquine is significantly less hepatoxic than chloroquine.

henriquez 7y ago

Exactly. Since the risks and side-effects are well-established, it’s more ethical at this point to experiment on humans with an “off label” usage. Doctors do that all the time with other meds.

_ph_ 7y ago
Yes, doctors should experiment with the drug and I am certain, a lot of those, who have the necessary conditions to perform a proper experiment, will do. 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).
- ekianjo 7y ago
  > Blindness This side effect occurs if you take chloroquine for extended periods of time. Look at the data. https://eyewiki.aao.org/Hydroxychloroquine_toxicity 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]. "
  - kevingadd 7y ago
    I'd note that the phrase "further retinal damage and visual loss" implies that retinal damage and visual loss has already occurred... how much of that you are willing to tolerate is up to you, I suppose: I'd prefer 0 unless necessary. If the retinal damage is saving me from a death at the hands of COVID-19 maybe it's worth it, but if it's not...
    - ekianjo 7y ago

raverbashing 7y ago

I have similar thoughts 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-megatrial-four-most-promising-coronavirus-treatments https://www.sciencemag.org/news/2020/03/who-launches-global-... (including CQ/HCQ)

jonathanstrange 7y ago

This is irresponsible. This drug has severe side effects, it makes absolutely no sense to prescribe it for a completely different disease without first confirming in clinical trials that it has positive effects. > 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.

_red 7y ago
You are currently running another experiment called: Crash the global economy. That's also irresponsible. Should 10-yr olds be forced to give their life to save 85 yr olds?
- JoeAltmaier 7y ago
  Maybe a bit of strawman there. With more information (hopefully coming) we should be able to make more nuanced decisions.
ekianjo 7y ago
> This is irresponsible. This drug has severe side effects 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 https://eyewiki.aao.org/Hydroxychloroquine_toxicity
- jonathanstrange 7y ago
  The suggestion on the table is to give this drug to extremely ill patients who suffer from a new viral disease on the basis of anecdotal evidence and without clinical trials. The suggestion was to massively prescribe it. 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?

hannob 7y ago

Opinions like this seem to be popular these days, but they're dangerous. Because this is an emergency we want reliable information. 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.

throwaway_pdp09 7y ago
Agreed, this kind of thinking comes from fear and desperation (and another kind is denial of reality - this can't be happening so it isn't. My neighbours still don't realise it's actually happening). If we want to deal with covid we should have started years ago. As ever, we didn't.
hanniabu 7y ago
> Because this is an emergency we want reliable information. So much for that given the president was recommending chloroquine to be used off the cuff.
pbreit 7y ago
"no reason to think that they couldn't have done that in the same amount of time with the same amount of effort" There is EVERY reason to think they were not in a position to a "proper" test. They are in the middle of an epidemic!
ping_pong 7y ago
They are in a war zone in Italy and presumably in the US very soon. If hydroxychloroquine is safe (except for some people with a known predisposed genetic condition), then we should be giving it widely and early. We can worry about the science and studies later on, but right now we need to save lives and decrease ICU overload.
tim333 7y ago
This was done in about a week. Where's an example of a clinical trial to your liking done that quickly?

httpsterio 7y ago

Being sick with a disease like Covid-19 could absolutely alter how a medication works on a person. The drug might be safe to a person with a certain profile and it has been tested against those, but each underlying issue is a new profile which it should be tested against as separately as possible.

guiriduro 7y ago
I think this is the fairest counter-argument I've heard so far about safety of HCQ in Covid-19. I still think the background of "you're in a house burning down, some tests tentatively indicate this may be effective..." weigh more against the risk of side-effects or worse progression due to CQ/HCQ. We ought to be able to devise some experiments to add certainty, using mainly retrospective data now available. 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.
dcolkitt 7y ago
Based on that reasoning, we shouldn't give any pharmaceuticals to coronavirus patients. Even simple fever relievers, like acetaminophen, or oral rehydration fluids should be prohibited because we just don't have enough data to know how they'll interact with COVID-19 specifically.

lultimouomo 7y ago

> 3/ people are oversaturating ICU right now. And as such, it is an emergency situation. 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.pdf http://www.simit.org/medias/1569-covid19-vademecum-13-03-202...

raverbashing 7y ago
Thanks for this reference, it seems they are proposing 2 potential treatments (p. 13) for the more severe patients > 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)
- dcolkitt 7y ago
  For the record since that decision day, the growth rate in the number of deaths in Italy has fallen in half[1]. In the 9 days from March 13 to March 22 the daily number of deaths grew 160% from 250 to 651. Prior to that, the same level of growth occurred in 4 days between March 9 (96 deaths) to March 13. That seems like pretty strong evidence that the new treatment protocol is drastically decelerating the pandemic in Italy. [1]https://www.worldometers.info/coronavirus/country/italy/ https://www.worldometers.info/coronavirus/country/italy/
  - lultimouomo 7y ago
    This does not make much sense to me. If it was effective, it should decrease the lethality rate, not the growth in the number of deaths which is much more affected by the actual number of cases. In the page you link you can see that lethality rate has not fallen. Also, as I wrote I'm pretty sure that I saw an earlier version of that document, dating IIRC to the beginning of the month, that prescribed more or less the same combination of chloroquine and antivirals as a first line treatment.

jpz 7y ago

It isn't vitamin C. It has a lot of side effects, including serious psychiatric ones in limited cases. If you give it to 100 people you're going to get new health issues that you didn't have before in that population.

jansan 7y ago
Interestingly there is a trial to use a high dose of vitamin C to treat COVID-19 ARDS: https://youtu.be/bt-BzEve46Y?t=2107 https://youtu.be/bt-BzEve46Y?t=2107

kingkawn 7y ago

You cannot pour a drug into the populace that will cause side effects on a mass scale that might also overwhelm the healthcare system. It is nice to imagine we have the medicine already, that we can simply wave our hands distribute the pills and everything can go on as it was before this. But we do not and can not go back.

wpietri 7y ago

This is absurd: > 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.

tim333 7y ago
Though why should it have weird side effects when used for COVID that it didn't when used for malaria?
- wpietri 7y ago
  As I said, drugs just have effects. Humans then look at the results, decide which are good and bad, and then label the bad ones "side effect". So I think the real question is: why do you think 100% of the novel effects will be later put in the "good" bucket?

m0zg 7y ago

Yeah, it's important to have it available if it's needed and it's important to conduct at least some sort of trial. Because the drug, combined with azithromycin is so fast acting, we should see the first results in a few days. Worst thing that can happen is it doesn't work. Best thing that can happen is we can save 1.8 trillion dollars and restart the economy. Under these circumstances one would be an idiot not to give it a try. Coughing your lungs out but feel like CNN is not lying to you? Easy! Refuse the drug. Nobody can force you to take it.

DanBC 7y ago
> Worst thing that can happen is it doesn't work. 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_query https://twitter.com/search?q=azithromycin%20qt&src=typed_que...
- m0zg 7y ago
  That's why they are starting with a trial, and not a full scale roll out. Other countries are using this combination of drug, and it's not because they're huge fans of Trump, I can assure you. We also have literally millions of devices out there capable of detecting arrhythmia - they're called Apple Watch.
  - snegu 7y ago
    Apple Watch can't detect long QT, which is one of the risk factors here.
    - m0zg 7y ago
      That's like saying construction N95 masks can't be used in the medical setting just because they lack appropriate certification. That old shibboleth has been defenestrated weeks ago. 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.

gus_massa 7y ago

> There's no need for establishing a benchmark. Just proper categorization of existing patient should be enough to compare. 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.

rsynnott 7y ago

> chloroquine is a very well known cheap drug. There is no new risk associated to using it that doctors arent already aware of. 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.

TheHypnotist 7y ago
We know the side effects for a healthy individual or those with malaria, but how do we know for certain this won't cause new problems in those with COVID-19?

mrfusion 7y ago

You’re absolutely right. We need to act fast.

jcrubino 7y ago

2) It complicates the treatment of the patients who will experience the worst cases of COVID-19 causing panic... people above 65 with diabetes and heart conditions. 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.

dcolkitt 7y ago
> Again this drug has well known precautions that reads like the all the people who will experience the worst of COVID-19 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.
- jcrubino 7y ago
  You missed the point. 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.

epistasis 7y ago

> 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. 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.

dcolkitt 7y ago
> 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. 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.
- akiselev 7y ago
  That only normalizes natural variances in your patients, not artificial biases introduced by the healthcare system. Pump and other hardware measuring out dosages might come from different manufacturers or be calibrated and serviced by different technicians. Maybe the study includes one too many hospitals in a region dominated by one manufacturer whose hardware tends to error more in one direction than other manufacturers. The generics used by pharmacies and hospitals might be slightly different because of local relationships. Exercise, ability to have visitation in quarantine, and other amenities in hospitals will have differing impacts on confounding factors like exercise and morale. And on and on. 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.

herf 7y ago

Check PDR before you say things like this: https://www.pdr.net/drug-summary/Plaquenil-hydroxychloroquine-sulfate-1911.7193 https://www.pdr.net/drug-summary/Plaquenil-hydroxychloroquin... 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-drug-touted-by-trump-musk-can-kill-with-just-two-grams 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.

aaavl2821 7y ago

Many doctors are already actively prescrbign this. I heard that it is basically de facto standard of care in France. Doctors recognize that when eveidence based medicine doesn't provide an adequate treatment, they need to improvise. Off-label prescribing is very common 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

eagsalazar2 7y ago

I imagine some country/region out there will adopt this approach so we'll all get to find out in a few weeks (possibly at their expense).

jansan 7y ago
It is being used in several countries already (US and Europe, not sure about Asia). If you are interested in details, here is a video of a conference call at UCSF: https://youtu.be/bt-BzEve46Y?t=3194 https://youtu.be/bt-BzEve46Y?t=3194

IAmEveryone 7y ago

Your second and third point are completely independent of the substance at issue. So by that logic, we should test everything that is “safe”. Prayer? Meditation? Garlic? Red wine? Cannabis?

perl4ever 7y ago
https://en.wikipedia.org/wiki/Generally_recognized_as_safe https://en.wikipedia.org/wiki/Generally_recognized_as_safe ...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.

naasking 7y ago

> There is no new risk associated to using it that doctors arent already aware of. You can't possibly know whether this drug would have adverse interactions with a new illness.