Efficacy of hydroxychloroquine in patients with Covid-19: a randomized trial
medrxiv.org
medrxiv.org
If there were such a thing as phase 5 trials with at least a million participants, it would be completely insane to use anything that had only undergone phase 3 clinical trials. People should make rational decisions based on the best evidence that's available at the time. Whether or not it's rational to take HCQ, there's nothing magical about phase 3 studies.
Antiviral drugs only really work in the first couple days of the illness, and with this disease you usually don't get symptoms until at least day 5. And in the current environment, no one is getting put on prescription antivirals until at least day 10, and usually even later. To me this raises the question of whether clinical trials are really even possible right now in the first place, or whether making decisions based off in vitro data is the best we can do for right now.
I don't think I understand this. We have a clinical trial with in vivo data right here though, right?
AFAIK there's no clinical trial data, but there is in vivo data. My point though is that these are drugs that block viral replication, and we're mostly only administering them after the virus has already finished replicating. So in that scenario of course it's going to look ineffective regardless of whether it actually works or not. I don't believe the data showing it works, but I also don't believe the data showing it doesn't work.
Also, why don't you believe the data? or is it the conclusions that the researchers draw from the data that you don't believe? The statistics and trial design in this paper seem to be sound.
The meaningful conclusion is "Considering that there is no better option at present, it is a promising practice to apply HCQ to COVID-19 under reasonable management."
Luckily, long-term use of the drug isn't necessary here because the immune system successfully responds with antibodies to fight of the virus, so retinopathy isn't an issue. Also, as the paper states, "Fortunately, deciding on individual treatment plans scientifically, monitoring adverse reactions timely, to avoid overdose, short-term application of HCQ is relatively safe."
This is one of the drugs on the large study WHO is running worldwide, and is getting a lot of attention. I'm sure we'll have strong evidence either way soon.
Of course, (and even though this probably isn't the case) if all this treatment does is make the mild and moderate cases (those without and with pneumonia and not needing supplemental oxygen) end faster, we can get to herd immunity that much quicker.
And yes, people are using this drug and are going to be using this drug at an increasing rate, so we'll have plenty of evidence soon.
From Paper:
TTCR: Time to clinical recovery
edit: got downvoted, so adding link to only other "absorption of pneumonia" use that I could find: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344839/
edit2: I could also find some usage of "absorption of inflammation", again also all Chinese researchers.
I will assume that 'absorption' in this sense refers to the fluid. It's a good thing when this happens, because that that area of the lung can be accessed by air again.
The French study, problematic in the extreme but still promising, claims a large synergistic effect of using both drugs in combination.
Also, unlike the French study, this one appears to be at least controlled, but possibly not blinded.
Not sure they've been doing proper studies and such because they're so slammed, but it seems they've been trying it in Italy and... maybe it helps some, but doesn't seem like it works miracles.
A doctor in NY has treated with that combination and is up to almost 700 COVID-19 patients without one dying _or needing a ventilator_.
Some relevant quotes:
>Dr. Zelenko said the whole treatment costs only $20 over a period of 5 days with 100% success. He defines success as “Not to die.” Dr. Zelenko first posted his Facebook video message last week calling on President Trump to “advise the country that they should be taking this medication.”
>There are many other success stories about hydroxychloroquine across the country. Last week, Dr. William Grace, an oncologist at Lenox Hill Hospital in New York City, said they’ve not had a single death in their hospital because of hydroxychloroquine. “Thanks to hydroxychloroquine, we have not had a death in our hospital,’ Dr. Grace said.
From:
https://techstartups.com/2020/03/28/dr-vladimir-zelenko-now-...
When people are dying in large numbers, sometimes "anecdotal evidence" (especially with large samples) is plenty.
This story was reported by Laura Ingraham on Fox News. Her tweet promoting this as a "cure" was immediately withdrawn by Twitter as "misleading". The 40 minute video interview with Zelenko, again on Fox News, was conducted not by a medical reporter, but by Rudy Giuliani. Zelenko goes on to make numerous huge dire public health predictions -- none of which a family practitioner has any business suggesting, especially in public on a national news outlet.
As always, consider the source of the information.
It's also very important to note that Zelenko was treating 700 unhospitalized patients; these were not cases severe enough to admit to a hospital. He treated them from his home (since he lost a lung to cancer years ago). So he never actually physically met with any of those 700 patients to monitor their progress.
In fact it's likely that many of these patients never tested positive, but simply self-reported as positive, further diluting the 'trial'.
And because 80% of positive COVID-19 cases are minor or even asymptomatic, the number of his patients that really _needed_ treatment falls from 700 down to, at most, 140 (20% of 700). That's a much smaller treatment effect that a large number like 700 would suggest.
It's also important to note that, apparently, Dr Zelenko treated sick people with medications that were NOT approved for the target disease. And he did so apparently without approval from any higher public health authority. In short, it appears that he experimented on his patients without authorization to do so from a public health or research authority.
Zelenko is a family medicine doctor, not a specialist in infectious disease or research. Thus it's very unlikely he wrote up an experimental design with proper safeguards, much less got it approved. With such poor experimental controls, it's impossible to interpret his results. What's more, if any of his patients later incur harm (like heart attacks from the chloroquine), such a laissez-faire approach to medicine will invite lawsuits galore.
No. Anecdotal evidence alone is NEVER enough.
Snopes has more details of side-effects etc: https://www.snopes.com/fact-check/zelenko-669-coronavirus-pa...
For anybody who's interested, here's an interview with the doctor himself: https://forward.com/news/national/442285/coronavirus-hydroxy...
https://twitter.com/yishan/status/1244717172871409666
https://twitter.com/yishan/status/1245066858597761024
If true, this argues for giving HCQ immediately upon admission.
https://blogs.sciencemag.org/pipeline/archives/2020/03/31/co...
TL;DR: better than the French paper but that's a low, low bar
Here the null hypothesis is that hydroxychloroquine isn't any better than not receiving anything. If the study
One thing that certainly should be cleared up is the age effect: they report "No difference in the age ... distribution ", but that's not enough.
If you are trying to say that their sample size was too small to find an effect using null hypothesis testing, then that makes no sense.
It's hard to see the president's statements as anything but an effort to promote himself by tying himself to this treatment. It should be non-partisan.
Previous administrations didn't try to set up "I win" scenarios in times of crisis. We need to be able to evaluate the treatment without it being clouded by the issue of whether one side or the other was right.
The UK government is led by a right wing populist by all accounts and this is what our daily breifing had to say on the matter "And in our determination to prevent as many patients as possible seeing their condition worsen we are conducting rapid clinical trials on those drugs, including anti-malarials, which may be able to reduce the impact of COVID-19 on those affected."
Contrast that with Trump's statements (by Twitter of course): "HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine. The FDA has moved mountains - Thank You! Hopefully they will BOTH (H works better with A, International Journal of Antimicrobial Agents)....."
If you can't see why there is a problem with the way Trump has spoken about these drugs then I'm afraid I've lost all hope.
I'd say that's a pretty damn partisan statement from our Commander in Grief.
Its much more enticing for Big Pharma to sell new patented solutions, so they will pay their PR mouthpieces (MSM) to "be cautious" of anything that doesn't achieve that end goal.
Seems a bit in odds with your claims.
(1) OP said big pharma wants to downplay HCQ because it doesnt make them as much money.
(2) reply says that the fact that pharma donated millions of doses contradicts that
(3) OP counters that pharma is donating millions of doses because it gives them an epic tax write-off
it has nothing to do with donations being bad. it has to do with the fact that pharma is always doing whats best for them, and if its also best for patients that's a happy coincidence, but they frequently act in opposite of whats best for patients (e.g. price gouging on insulin, in this case possibly downplaying the efficacy of a cheap drug HCQ), and that's something we should notice and call out
I have no problems believing that BigPharma does what is good for BigPharma in this case getting good PR, a tax write off and having their most valuable customers as in those with chronic conditions which means pretty much most people once they hit 50-60 to stay alive so they can sell their patented drugs to their insurers and HMOs is a much more believable strategy than some conspiracy that BigPharma is downplaying HCQ because they can’t make money on it.
- I'm not committed to this particular conspiracy theory but I jumped in here because I don't like when people try to dismiss conspiracies out of hand as if it's crazy to think that pharma does things like this constantly. There's this free market ideology that exonerates companies and argues that self-interested behavior leads to positive outcomes, so I was reacting to what I sensed of that
Thought I was asking for clarification. What goalposts did I move?
That seems like a non sequitur... Do you think HCQ knows that, and is therefore making itself less effective, just to stick it to Trump?
The reality is, HCQ is not without adverse side-effects, and we have reason to be cautious. There have been several examples in the past where early results of HCQ testing looked promising against various viruses, but didn't pan out when actually used at larger scale in humans.
The press did.
The mainstream US media has become a one-sided partisan cheerleading squad for the Democrats, and most Americans are sick of it. We'll see how that works out in November.
They broadcast almost every word Trump says, largely uncritically[1], with frequent "Today is the day he became President" epiphanies whilst minor Democrat issues are blown up into huge talking points and controversies that last for months.
How the chuff are they a "one-sided partisan cheerleading squad" for the Democrats?
[1] There'll occasionally be a "these things aren't true" afterwards but it doesn't stop them broadcasting them first.
I wonder if after all this is over, if our methods of modern science are changed forever, or if we just revert to where we were before.
In this kind of crisis, the last thing we need is to be injecting politics into the decision about which treatments are most effective.
No responsible person should offer unproven medical advice IN ANY WAY. And no medical professional should do so unless they have multiple reliables sources to support their advice.
Trump failed on both of these points. If chloroquine turns out to fail, he'll surely promote more possible treatments again and again, thereby whittling away public trust and hope, over and over. That's terrible leadership, and rightly merits criticism from everyone who gives a damn, not just "the other side".
That is what "the other side" was saying.
Difficult to watch, as someone familiar with chloroquine, knowing they were spreading mistaken information about the side effects and blowing the risks well out of proportion.
I repied to somebody saying essentially the same thing as you here: https://news.ycombinator.com/item?id=22760840
I strongly dislike the administration generally, but I've been perplexed as to how eager everyone has been to attack him over this particular incident. And if it was made partisan, it seems like it was done so by others, and not the administration itself.
And? As I said, there has been some anecdotal evidence coming from countries like China, SK, and France indicating it could help. It shouldn't be a strike against a government official for sharing potentially important information. At a certain point we need to stop blaming people in positions of authority for the stupidity that exists among individuals in society. I'd rather my government be open and transparent than hide information from me because the more idiotic portions of the population may react poorly.
Its also worth noting that Hydroxychloroquine is unavailable in the US without a prescription. The "panic-grab" you are seeing is entirely due to physicians buying for themselves and their family/friends. Definitely sleazy, but they are hardly uninformed.
> Unfortunately even the CDC was saying we don't have evidence supporting it.
The CDC has proven itself to be conservative and slow to the point of harmful ineptitude. A huge part of the reason the situation in the US has diverged so much from countries that have managed to successfully clamp down on the disease (like SK) is because they insisted that testing rely on their own, overengineered procedures, and because they've insisted (for at least a decade now) that masks are only beneficial for HCPs, despite numerous studies to the contrary and the advice of nations like those in East Asia. Now, after the cat is well out of the bag, they've opened up testing to private companies and other testing procedures, and are now beginning to say that regular people should in fact be using masks to prevent the spread of the disease.
An appeal to authority is a fallacy on the best of days. Its even worse when said authority is in the midst of the most incompetent moment in its history.
Even if that wasn't a ridiculous stretch and was actually happening, that's on the shitty doctors, not the president.
He simply reported that it looked promising in early studies, like we had already seen reported here on HN. His other action was apparently to lean the FDA to find out ASAP rather than heming and hawing for years following standard beaurocratic protocols. I think it was fine to do both those things. Responsible even.
We don't want scientific investments made because the president seems into them. We want those choices made by experts who are hopefully disinterested as possible. We want them considering the most likely successful treatments from their expert point of view.
You essentially can't have that now. And this goes beyond influence. The administration has been leaning on the FDA to give this ememgency approval.
This appears safe from the very preliminary studies we have but problems can develop at scale. These drugs are known to cause heart rhythm issues. It's conceivable that deploying then at scale in an emergency could lead to increase in fatal cardiac episodes. Were this drug not to actually work, large scale deployment would almost certainly do more harm than good.
The presidential podium confers added weight to everything a person says for good or ill and therefore should be used cautiously.
I don't think the boards of medical quality assurance of the 50 states care enough about public statements to yank the license of (or even to discipline) a doctor for making a public statement the doctor knew to be false. In general the US medical profession doesn't have the commit to truth that, e.g., physicists do.
No, hes a guy charged with making high level decisions in a crisis. He also has some very competent advisors at places like the NIH, FDA, CDC etc... I dont think he was just some redneck responding to a tabloid article.
If the doctor now publicly claiming 699 treatments with 0 deaths using HCQ turns out to be a blatant fraud I think he may well lose his license given the situation.
But yeah, let's fuck around and try nothing and see how that goes.
The odds seem good on that one.
"Zelenko’s claims, however, rest solely on taking him at his word: He has published no data, described no study design, and reported no analysis."
HCQ can only be obtained via a doctor's prescription. If there is a shortage of HCQ, its because actual physicians are writing it more, either for their own benefit or for their patients. This isn't the average person panic buying toilet paper. Its trained medical professionals. If you are implying that they are incapably of thinking rationally and professionally in response to a short, offhanded comment by the President, then the issue is far graver than anything Trump is saying.
> led to at least one death
Which occured because an elderly couple saw the news, realized that HCQ is in a chemical used to treat their fish tank, drank it, and one of them died. If I read an article saying a drinking alcohol in moderation can reduce heart disease, and in response I go out and chug a bottle of isopropyl alcohol, the consequences wouldn't be blamed on anyone but myself. If anything, it supports the idea that any partisanship in this situation is coming from those who are trying to pin every instance of something bad occurring, literally at the level of a single idiotic individual, on the POTUS.
I find the "political" vs "non-political" distinction facile anyways.
Off-label usage is bad when this is a drug that other people (like those with lupus - see here [0]) need to survive - we need trials first and I'm not sure that is occurring due to the President. This is a problem created by too early messaging when you should be focusing on "stay home" and other clear communication that was absent for weeks before his focus on this drug.
[0]: https://www.cnn.com/2020/03/31/opinions/hydroxychloroquine-c...
Let's not let the media tear us apart. Not everything is Trump's fault. Not everything is America's fault. And sometimes people who are not Trump or countries that are not America make bad decisions that cost lives. Let's acknowledge these basic facts and work together.
California and Texas seem to be making better choices than NY and Florida. America seems to be doing better than Italy and Spain but worse than Germany. It's not really a partisan thing and it's not really a national identity thing. It's an issue of who in what regions acted strongly enough, and when.
America is a federal system, so we would expect variance between the states, and that's what we're seeing. Same as in Europe. The federal government plays an important role (like preventing test kits from being developed outside the CDC -- bad -- and early travel restrictions -- probably good), but not the only role, and it shows.
He wanted people (in case it panned out to be good) to attach his name to CQ and HCQ. That is selfish.
This issue is partisan only if partisans act unthinkingly. The press had damned good reason to act as it did. The 'administration' did not.
How is it not the administration's doing then?
But now it seems clear that the accusations were absolutely accurate, and the distinctions the author tries to draw are irrelevant.
It is very unfortunate that the media politicized this treatment in such a way that now everyone who dislikes Trump carries an initial bias against it.
Antiviral drugs will always be given to late in this disease case, maybe it can reduce infectuosity but we don't know enough yet.
Maybe giving it to everyone to prevent the disease before its even there could be helpfull, but if i had to take HCQ, i will have to stop taking my antihistamine drugs, and going into april/may, this is a big no for me.
The fact that it can also reduce the autoimmune reaction is really interesting though, so maybe giving it to mild cases will prevent them to destroy their own cells, but this is also dangerous as the disease can cause myocard lesions (probably the autoimmune reaction, but we don't know yet).
In any case, talking about it is useless before more data arrive: even if we could give HCQ to everybody, the lockdown is still necessary until the first wave decrease (at least in France). Don't forge an opinion on something this early, it will be hard to let it go if you're wrong, and being right early don't give you anything.