
Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients - Cantbekhan
https://www.medrxiv.org/content/10.1101/2020.04.10.20060699v1
======
capnrefsmmat
It's important to interpret these results carefully: "no evidence of efficacy"
does _not_ imply evidence of no efficacy, and in fact the uncertainty in this
study is quite large. The sample size is small enough that it would be very
hard for this study to detect the effect of hydroxychloroquine unless that
effect is very, very large.

From the abstract:

> In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-
> HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%,
> respectively, developed acute respiratory distress syndrome within 7 days
> (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00).

The relative risks and confidence intervals are the important numbers here.
For example, the relative risk for death is 0.61, meaning the observed risk of
death was lower for patients treated with hydroxychloroquine -- but the
confidence interval is 0.13 to 2.89, meaning the data is consistent with
anything from the risk being much smaller to the risk being much _larger_.
Since there were only 3 deaths in the treatment group and 4 deaths in the
control group, it's very hard to draw precise conclusions about death rates.

I think we can interpret this result to mean that hydroxychloroquine doesn't
have a miraculously large effect, but the evidence is weak. Other commenters
are correct that large randomized trials will be more definitive.

(disclaimer: I am a statistician, not a doctor)

~~~
thedudeabides5
This is a great comment thanks.

Title of the paper could (with a tongue firmly in cheek) be called, _" Weak
evidence for effectiveness of hydroxychloroquine but our sample was likely too
small for it to pass a T-test"_

~~~
magicalist
> _Title of the paper could (with a tongue firmly in cheek) be called, "Weak
> evidence for effectiveness of hydroxychloroquine but our sample was likely
> too small for it to pass a T-test"_

It would be irresponsible to choose an experimental design (like significance
level) and then use wishy-washy language ("weak evidence") to work around it
when the study criteria aren't met.

This would be more akin to the headline from the press release for the study
from the university PR office.

~~~
dhimes
In the US the phrase "tongue-in-cheek" means "kidding."

~~~
magicalist
> _In the US the phrase "tongue-in-cheek" means "kidding."_

I took that to mean they obviously weren't suggesting something so
conversational as the actual title, but the takeaway is the same and shouldn't
be a conclusion taken from the OP comment.

------
apendleton
Personally I'm witholding judgment until the results of the PATCH trial
([https://clinicaltrials.gov/ct2/show/NCT04329923](https://clinicaltrials.gov/ct2/show/NCT04329923))
arrive, as it'll finally give us some decent statistical power, and be a full,
double-blind RCT. It also has multiple study arms (health-care worker
prophylaxis, home-quarantined early stage, hospitalized later-stage), so if it
turns out that HCQ is effective but that by the time patients are hospitalized
it's too late, as some are now suggesting, we should finally know with some
degree of certainty.

~~~
koheripbal
Yeah, the devil is really in the details about exactly when and how you
administer it.

Doctors are already saying that it's definitely no magic bullet, but they
debate whether it is effective at a certain stage of illness.

What I don't understand is why we're focusing so much on this specific drug
when there are some great antivirals out thee that have a more effective
theoretical mechanism of action. (eg Remdesivir)

~~~
lonelappde
Because it's become an arbitrary political football to separate "left" vs
"right"

~~~
SlowRobotAhead
As insane as that is.

And how funny is it (at least to me) that this is only because Trump came down
on one side initially. If he had come out saying exactly the opposite, that
HCQ was bad and we should be skeptical, everyone hoping it doesn’t work now
would be looking for the 10 person studies saying it totally works and
defending its use.

It’s almost beyond reason how hyper partisan this specific issue is.

~~~
rsynnott
This isn't left vs right; it's an unqualified politician vs pretty much all of
the scientific community.

~~~
koheripbal
This is not accurate and kind of exposes your own bias.

If you listen to virologist podcast, TWIV, they talk about the effectiveness
of HCQ. They aren't all "it's amazing!", but they do not make the claim that
it doesn't work.

------
w_t_payne
Given that I need hydroxychloroquine to treat my rheumatoid arthritis, I'd
like this hypothesis to be either proven or disproven as rapidly and as
unambiguously as possible.

~~~
AlexandrB
Because HCQ’s efficacy was briefly endorsed by a controversial political
figure I fear that there’s no evidence in either direction will convince the
true believers. This is now a political issue, like global warming. Hopefully
someone is ramping up production so availability improves for those that
actually need it.

~~~
jsight
Imagine if Obama had "endorsed" Biden using the same language. Would you have
considered it an endorsement? I find the interpretation of what he said to be
very peculiar.

~~~
CydeWeys
What is the comparison being made here? Endorsing the frontrunner for
political candidacy isn't remotely the same as endorsing an unproven drug to
treat an ongoing pandemic.

~~~
jsight
Noone endorsed an unproven drug.

~~~
ModernMech
[https://twitter.com/realDonaldTrump/status/12413672399007785...](https://twitter.com/realDonaldTrump/status/1241367239900778501)

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).........be put in use
IMMEDIATELY. PEOPLE ARE DYING, MOVE FAST, and GOD BLESS EVERYONE! @US_FDA
@SteveFDA @CDCgov @DHSgov

That's not an endorsement?

~~~
munk-a
For a comparison (to the original point made above):

Joe Biden has a real chance to be one of the biggest game changers in the
history of this country. The Democratic party has moved mountains in their
support of them - Thank You! Hopefully he will take office IMMEDIATELY. PEOPLE
ARE LOSING FAITH, MOVE FAST, and GOD BLESS EVERYONE! @US_DNC @JoeBidenPrez
@POTUS @IowaElections

------
forgingahead
This whole debate is insane to me -- some people that so-called "experts"
don't like mentioned HCQ as a possible treatment for coronavirus, and we've
ended up in some bizarro world where everyone is shouting and fingers are
being pointed over something that really shouldn't be controversial or
perceived as some sinister plot to destroy clever society.

1\. HCQ has been used for many decades

2\. The side effects are generally known

3\. It may have a positive impact on COVID-19, and it may not.

4\. Nobody is suggesting long term high doses for anyone, COVID patients or
otherwise.

5\. If people are severe patients of COVID-19, this should certainly be tried
as a treatment as long as the patient (or immediate family) is briefed on the
potential side effects. The alternative, potential death, makes this a worthy
discussion for a doctor/patient to have, with families being allowed to err on
the side of right-to-try. HCQ is cheap, available, and has been used for
decades.

The fact that "no evidence HCQ works!!" has 200 points of upvotes and counting
_when the sample size for this study is 181 patients only_ just shows how high
the temperature has become.

Everyone just calm down. As capnrefsmmat has eloquently pointed out, "absence
of evidence" does not mean "evidence of absence".

If you enjoy the thrill of debates for debates sake, here are other potential
topics for you: Whether masks are effective, condoms, seatbelts, helmets, or
even parachutes[0] _:

[0][https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC300808/)

_Favourite part:

 _Results_ We were unable to identify any randomised controlled trials of
parachute intervention.

 _Conclusions_ As with many interventions intended to prevent ill health, the
effectiveness of parachutes has not been subjected to rigorous evaluation by
using randomised controlled trials. Advocates of evidence based medicine have
criticised the adoption of interventions evaluated by using only observational
data. We think that everyone might benefit if the most radical protagonists of
evidence based medicine organised and participated in a double blind,
randomised, placebo controlled, crossover trial of the parachute.

~~~
DangerousPie
1\. Not for coronaviruses.

2\. They are known but they are by no means mild. A trial in Brazil just got
aborted due to severe heart problems.

3\. So does almost everything. If that's your threshold for taking a drug then
I have a lot of homeopathic remedies to sell you!

4\. Actually the doses given for COVID are often higher. Not sure what long-
term has to do with anything.

5\. That assumes that the risk of side effects is zero. It's not. Also, there
is an opportunity cost to taking HCQ instead of something else.

I totally agree with you that we should do proper trials on this and see what
happens. But right now there is zero evidence that it actually works, and some
(admittedly low-quality) evidence that it might not.

~~~
ddebernardy
> Actually the doses given for COVID are often higher.

Not just higher. The original article (the one out of China) that mentioned
that there might be some positive effects reportedly suggested using doses
that were a whopping 5 times higher than the usually prescribed amounts:
500mg/day vs the usual 100mg/day.

What more, the same article put forward that the drug was considered generally
safe and without any potentially troublesome side effects. That raised more
than a few eyebrows amongst the medical staff who knew the drug.

------
DoreenMichele
This study is specifically about patients sick enough to be put on oxygen. The
top ranked comments don't seem to address that detail.

Some thoughts:

My understanding is this is a powerful alkaloid. My experience has been that
similar compounds can help combat inflammation. They also can work to help
kill infection at times.

By the time people with Covid19 need oxygen, inflammation doesn't seem to be
the primary problem. So I wouldn't think it would be particularly helpful at
that point.

Ventilators get prescribed in part on the assumption that inflammation in the
lungs is a major impediment to getting sufficient oxygen. Ventilators are
failing at a shockingly high rate, with a death rate up around 80% or so. Some
doctors are moving away from ventilators because the death rate is so high.

I spoke recently with a researcher who suggested impaired vasodilation was a
possible explanation for the reports of low oxygen combined with a surprising
lack of pneumonia and inflammation in some cases and that makes a lot of sense
to me. The mechanism causing low oxygen does not appear to be the obvious
answer of "lung inflammation and pneumonia."

That doesn't mean this drug can't play a meaningful role at some stage. It
mostly means it's not the magic bullet solution for advanced cases that they
were hoping for.

This in no way surprises me because the things it actually treats do not
appear to be the cause of low oxygen in advanced covid19 cases.

~~~
firasd
You might find this thread interesting (“There's a growing body of data to
strongly suggest #COVID19 predisposes to both venous and arterial
thromboembolism due to excessive inflammation, hypoxia, immobilization and
diffuse intravascular coagulation.”)

[https://twitter.com/scottgottliebmd/status/12500696095810314...](https://twitter.com/scottgottliebmd/status/1250069609581031428?s=21)

~~~
DoreenMichele
Thank you. It is interesting stuff and fits with some of my impression that
they are overlooking important blood-related issues. Anemia (a blood disorder)
is also a cause of low oxygen. That's not exclusive to lung function.

Glad to see some doctors are working on that angle. (crosses fingers, hopes
for better treatments soon)

------
jeffdavis
Given the study's small sample size, it seems the only way it would have
produced a conclusive result is if the effect size was huge (i.e. miracle
cure). The study found some evidence of efficacy, but it was not significant
given the sample size.

A better headline would say something like: "study finds that HCQ is not a
miracle cure for already-hospitalized covid-19 patients".

~~~
mcguire
How much are you willing to pay for "not a miracle cure" on the basis of "eh,
it can't hurt"?

~~~
jeffdavis
Your point doesn't really make sense, because the purpose of a study like this
is not for making treatment decisions; it's for making research decisions.

I don't see anything in the study that discredits HCQ as a potential
treatment, and therefore it makes sense to keep researching.

------
wyxuan
This trial wasn't randomized, but a quasi randomized trial for HCQ whose
preprint was leaked is
here:[https://www.dropbox.com/s/8b2govfsa6n0xbq/NEJM_Clinical%20Ou...](https://www.dropbox.com/s/8b2govfsa6n0xbq/NEJM_Clinical%20Outcomes%20of%20Hydroxychlorquine%20in%20Patients%20with%20COVID19.pdf.pdf.pdf.pdf?dl=0)
Study indicates that one adverse effect of HCQ (on top of not improving
patient outcomes) is increased ventilator times.

~~~
onlyrealcuzzo
From the paper:

A total of 63 patients were included with 32 in the hydroxychloroquine arm.

Hydroxychloroquine administration was associated with a need for escalation of
respiratory support level compared to those that did not receive
hydroxychloroquine at 5 days (p=0.013). The same findings were observed in a
baseline-matched subgroup analysis. Absolute lymphocyte change in the
hydroxychloroquine group was no different than supportive care alone
(p=0.413).

Hydroxychloroquine use trended towards worsening neutrophil-to-lymphocyte
ratio compared to supportive care alone (+9.59 vs +1.58, p=0.51) as well as a
higher risk for intubation (p=0.051).

~~~
layoutIfNeeded

        p=0.413
        p=0.51
    

So, basically coin toss?

~~~
onlyrealcuzzo
You overlooked the major finding of the study:

> Hydroxychloroquine administration was associated with a need for escalation
> of respiratory support level compared to those that did not receive
> hydroxychloroquine at 5 days (p=0.013).

> p = 0.013

------
bretpiatt
Lots of conflicting research happening[1], until we get multiple controlled
trials we won't really know. Here's one that shows improvements.

[1] French ~50 patient study that tried Control, Hydroxychloroquine, and
Hydroxychloroquine + Azithromycin combo: [https://www.mediterranee-
infection.com/hydroxychloroquine-an...](https://www.mediterranee-
infection.com/hydroxychloroquine-and-azithromycin-as-a-treatment-of-covid-19/)

~~~
war1025
> Lots of conflicting research happening

That's my main take-away at this point. I have seen enough reports saying it
worked, and enough saying it didn't that I believe the answer is probably
somewhere in the middle.

My understanding is the best guess for how it works is by keeping the viral
infection from becoming serious enough to require hospitalization. Similar to
how proper treatment of wounds early on keeps them from getting to the
gangrene stage where you need amputation.

Unfortunately, politics. So the Left wants it to be completely no use at all,
and the Right wants it to be a miracle drug. Most of the population really
probably just wants effective treatments if they end up getting sick.

~~~
the_af
I'm out of the loop here: why would _any_ political faction not want an
alleged cure to work? What's the goal here?

~~~
downerending
Trump pushed it as a miracle cure, at least at one point, and he evokes bitter
opposition in many.

(I think this is quite irrational, but that's your answer.)

~~~
Goronmon
People are in opposition to the president promoting drugs with unproven
effectiveness as a miracle cure for an ongoing pandemic.

I didn't think testing drugs before giving them to people was considered
"irrational" as you state, but I guess that is where we are now.

~~~
downerending
It's "irrational" to oppose an idea just because it comes from someone you
despise. It's not like this is coming from the _National Enquirer_ \--he has
access to some of the brightest minds in the world.

The efficacy picture on these drugs is quite confusing, and it's not out of
the question that they will turn out to be crucially useful. Giving up on them
without further investigation doesn't seem wise at this point.

Beyond that, sometimes being a leader means giving people hope, even if that
might involve shading things. Trump may not be an Adama, but I _do_ think he's
pretty good at making people feel better, or at least distracting them from
their troubles. And right now, that probably _is_ saving lives.

~~~
fzeroracer
Let's say Trump instead proposed that people taking, I don't know, silver
supplements was a proper treatment for covid-19.

Would you say it's irrational to oppose that idea? I mean it's not been proven
to not work, so you gotta try anything you can, right? And he's giving people
hope.

~~~
downerending
If a lot of scientists world-wide were looking at it, yes, I would think that
irrational to not consider silver supplements. As far as I know, Trump has
never advocated taking any drug without medical guidance.

We were (and largely still are) dealing with a _lot_ of unknowns. As far as
I'm concerned, everything is on the table, as a possible improvement.

~~~
Goronmon
Isn't one of his quotes _" It's been out there for a long time. What do you
have to lose?"_ though I guess he does followup by saying he will talk to his
doctor before he takes it. But the overall sentiment makes me pretty
uncomfortable.

------
bcrosby95
And to put this interpretation into perspective, people that need this drug
for diseases that it has proven to have a large effect on are losing access to
it because it may or may not help with COVID-19.

~~~
3fe9a03ccd14ca5
HCQ is an off-patent drug that is produced in every major country in the
world. In fact, many countries have stockpiles of it because of its efficacy
at preventing malaria.

If there’s a risk of a supply run, it would definitely not last very long. For
many people there’s alternatives for treating arthritis and lupus.

If it’s shown even to improve the patient’s outcome by even just 10% or more
(as this study suggests), every country should be ramping up production of it
right now instead of letting it be politicized.

~~~
rozab
Face masks have been shown to be effective at controlling pandemics, and
apparently no one (in many western countries) thought to stockpile those.

~~~
adventured
> Face masks have been shown to be effective at controlling pandemics, and
> apparently no one (in many western countries) thought to stockpile those.

You're dropping the context of the hard decisions nations and governments
actually deal in day to day, year to year when it comes to budgets. That's why
not a single country had a proper stockpile of N95 masks for a pandemic like
this. That isn't an exaggeration: literally not one nation had enough of a
stockpile for this scenario, that includes South Korea, Japan, China.

To say that nobody thought to do it is outlandish. As one example Congress set
aside funds in 2006 to stockpile 100 million N95 masks. That's not strange, as
_many_ people were aware of the need to maintain such a stockpile. There is a
big difference between being aware of the need, proposing plans and spending
for it, and actually getting billions of dollars on a recurring basis to
maintain the necessary proper stockpile perpetually with no event to push it
with (yeah but we had a flu pandemic in 1957! try selling that premise).
That's the actual reality of budgets and governments.

It's expensive to maintain a persistent _minimum_ stockpile of 1 billion non-
expired N95 masks to cover the US population and the demand the US has seen.
If it's a year-long pandemic, a billion masks isn't enough. You need several
billion masks in that scenario. Coming out of the great recession, that is a
very hard budget decision for all nations. And the fact is, most nations can't
afford to do it at all. The easy retort of course is to say, well, look at the
damage from this virus compared to that cost for masks. That's purely
hindsight spouting that tries to pretend a comprehensive reality doesn't exist
and that people who make budgets don't have to deal with difficult decisions
every single year (while not factoring in every possible bad scenario every
time they make a budget).

And let's not pretend it's enough to stockpile masks, regarding spending
allocations. If we're doing hindsight fantasy, let's be correct about it. You
need to constantly maintain a lot of other gear and training for a pandemic,
costing large sums of money. In an ideal scenario a nation the size of the US
should probably have over a million ventilators stockpiled, just in case. We
should probably maintain 2x or 3x the ICU capacity we have, on a persistent
basis and at a large cost.

This isn't an argument against being more prepared. Of course every nation
should have a vast magical stockpile of N95 masks that never depletes, even
the ~140 poor nations of the world that can't afford to do it. The point is,
it's difficult to convince any nation to do it at the required persistent
scale, and most can't afford to do it regardless.

~~~
kyboren
I strongly agree with everything you wrote.

I think there is an alternative solution, though: Rather than maintaining a
gigantic stockpile large enough to last a multi-year pandemic, it might be
more efficient to maintain a modest stockpile sufficient for the breakout
phase along with ready-to-deploy crash production capacity. This might be
significantly cheaper.

This means that we need to ensure that we have the capacity to 100x, 1000x,
10,000x production--whatever is modeled to be enough to meet ongoing demand
during a pandemic--within the time bought by drawing down the strategic
reserve.

We don't need to maintain and refresh a complete stockpile of finished goods,
or even a complete stockpile of production capacity (suitable factory floor
space, meltblown nonwoven fabric equipment, etc.). We just need to know
_where_ such things exist that can be quickly directed to the desired use
either with cooperation from the owner or with the DPA, how much exists
naturally, and only if there is a deficit, to maintain a stockpile sufficient
in combination with those identified supplies: Government-owned sterile
factory floor space, for example, or spare production lines for meltblown
nonwoven fabric.

We can even enlist private companies to maintain the stockpile for us. It
makes way more sense to just subsidize e.g. 3M to have lots of extra meltblown
nonwoven fabric production capacity. They are in the business, they maintain
and operate the machinery and have the know-how and commercial connections to
produce and distribute the material. They will have the capability to quickly
respond to demand spikes if the capital requirements for increased production
capacity already exist thanks to Uncle Sam's foresight.

Finally, what is maybe even more important than stockpiles or production
capacity subsidies is the organization this exercise entails (knowing who
makes what critical parts in the supply chain, where they are, what their
production capacity is and how quickly it can grow, etc.), which gives an
ability to rapidly marshal resources and eliminate inefficiencies to surge
production as quickly as possible.

------
Medicalidiot
It was observed that between 7% and 28% of hospitalized have acute myocardial
injury [1-4]. When one looks at Epocrates (database for drugs which is why I'm
not linking anything here) the severe adverse reactions of hydroxycholoroquine
include QT prolongation, cardiomyopathy, and torsade de pointes. Just to
define some things here, QT prolongation is the time from your Q wave to your
T wave, or the start of an electrical depolarization on your cardiac
ventricles to repolarizations. QT elongation usually leads to cardiac arrest.
Torsade de pointes is a syndrome where your cardiac ventricles beat so quickly
that your heart paradoxically cannot fill up with blood potentially, and
usually, leading to sudden cardiac death.

Giving someone who has had essentially a heart attack (by definition COVID
patients have elevated troponin which is the marker we use to assess if one
has had a heart attack) is probably a bad idea so my question is: why would we
celebrate a drug that has massive cardiac adverse effects as a side effect?
Don't get me wrong I understand that there are drugs that are even worse.
Cyclosporine is the first line immunosuppresant for kidney transplant. Do you
know what one of the most common adverse effects of cyclosporine is? Kidney
failure. But we don't know what is causing the kidney failure in a kidney
transplant (rejection vs adverse effect) so we have to biopsy. Kidney biopsy
is a very invasive procedure, FYI. My point is, maybe waiting for double blind
placebo research here is the best case. Also, I made this exact same point on
here a month ago and people told that they would take my dose if it came to
that and at this point I will say go ahead.

[1]
[https://www.ncbi.nlm.nih.gov/pubmed/32169400](https://www.ncbi.nlm.nih.gov/pubmed/32169400)

[2]
[https://www.nejm.org/doi/full/10.1056/NEJMoa2004500](https://www.nejm.org/doi/full/10.1056/NEJMoa2004500)
[3]
[https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.0...](https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.046941)
[4]
[https://jamanetwork.com/journals/jamacardiology/fullarticle/...](https://jamanetwork.com/journals/jamacardiology/fullarticle/2763524)

~~~
danans
> between 7% and 28% of hospitalized have acute myocardial injury

So, for a younger (< 60) otherwise healthy person whose chance of death with
covid is less than 1%, it would seem ill advised to take this medication at
the onset of symptoms, unless the the disease itself causes similar or higher
rates of heart damage.

~~~
CydeWeys
It's only advised if it actually works. If it doesn't work, then there's still
no point in taking it because the side effects are still bad. And there's no
good evidence that it even works, and some mild evidence that it doesn't.

~~~
danans
Yes, and _even if_ it did work to reduce severity of the illness (agreed that
there is no evidence of this), it seems like for low-risk people, the risks of
heart damage outweigh the benefits of taking it. After all, what's an extra
week or two of illness vs a 7-28% chance of heart damage.

~~~
CydeWeys
Yup. I'm in a relatively low risk factor group and got over COVID-19 at home,
no hospitalization necessary and nothing stronger than acetaminophan needed. I
don't think a decent change of permanent heart damage was what I needed
through all this. Also, I would have had a higher chance of being hospitalized
from the side effects of the HCQ than from the COVID-19, which is really not
what the hospitals need right now.

The HCQ doesn't seem remotely merited based on its potential side effects
unless you are in a higher risk factor for the disease, and of course even
then, it's only merited it's actually efficacious (which it's seeming so far
it isn't).

------
jonplackett
Why is it taking so long to do a big study on this?

There are so many sick people and it’s a cheap drug and only takes a week Or 2
to see if it works.

Can someone please just do a Really large trial, like, 2 weeks ago so we can
put this to bed one way or the other.

------
mekoka
I think it's too bad that this drug has been so politicized. It's really
unfortunate that its two original and most prominent champions are people that
are so disliked. So many people spoke up (maybe prematurely) against it in a
knee-jerk reaction to its advocates. Now many act as if they're more concerned
about being right to ridicule the claims all along, than they are about
whether the drug is actually helpful in fighting COVID-19. Which, for the rest
of us without a stake in their stupid political feuds, is all that matters.
And because of this idiotic battle of the egos we could be passing on
something useful.

So here we all are, hanging by the edge of our seats, waiting for definitive
proof that _HCQ does not help in fighting COVID-19_ and we keep getting these
half-assed reports, seemingly more aimed at pushing a narrative than to
present (or eliminate) an option in a fight.

One of the latest examples is the account of Rita Wilson (wife of Tom Hanks)
who survived what seems like a difficult case of COVID-19 and shared her
experience with the media: she felt very tired, extremely achy, uncomfortable,
didn't want to be touched, on the ninth day her fever climbed up to 102 and
she had chills like she'd "never had before" (her words), she lost her sense
of taste and smell. Then she was given chloroquine, her fever broke (it's not
clear how long after). She goes on to warn against the "extreme" (her word)
side-effects she attributes to chloroquine: she was completely nauseous, she
had vertigo, she could not walk and her muscles felt very weak. She then
concludes that although her fever broke after been given chloroquine, she
doesn't know if it helped or if it was just time, which is fair. What do you
imagine the headline for that story should be? Well, to save you the trouble,
most read like this _Rita Wilson warns against "extreme" side-effects of
chloroquine_.

Are HCQ/CQ effective? We're still sitting here like idiots not knowing. If
they are, should they be taken carelessly? Definitely not, we already got
that, thanks, but _that is not the point_. We can't afford to have an "all or
nothing" mindset with these drugs as we did with masks. Simply proclaiming
that HCQ is useless because it is shown not to reduce viral load is just the
best way to pass on some other ways it might be helping. If it is shown to
have other palliative effects that actually help patients in their fight, such
as reducing inflammation or helping cope with high fever long enough for your
immune system to do the job, it's not _nothing_. It's information. It's an
option.

------
mfer
It's important to note that this study did not evaluate or note that
Hydroxychloroquine had no effect on all people in all situations with
COVID-19.

This was a targeted study looking at a specific circumstance. The situation
was "all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and
requiring oxygen ≥ 2 L/min"

So, adults who were not on oxygen are not included in the study. How does it
pertain to them? That's not covered by this.

It reads like it's saying people who are in bad shape and on ventilators did
not have a positive impact by Hydroxychloroquine.

This still leaves open questions like, can the use of Hydroxychloroquine lower
the rate of needing to get on a ventilator.

I look forward to someone reproducing this study and looking into the other
areas.

------
tgafpc2
"collected data to _emulate_ a target trial" I take it this means it's not an
actual clinical trial, just a virtual trial? What's the point? Of all the
people that died, none were saved by the drug. Sounds like an insurance ad.

------
cameldrv
The study is way underpowered (too small a sample). Based on the raw numbers,
the HCQ group had less deaths and less ICU admissions, but the numbers we're
talking about are 3 vs. 4 deaths and 16 vs. 21 ICU admissions (group sizes
were different).

These numbers simply aren't enough to make a determination one way or the
other. On mortality, the 95% confidence interval allows for a range of HCQ
reducing death rates by 87% up to it increasing death rates by 2.9x.

------
julioo
Point is that the study is done at the wrong stage, too late.

~~~
CydeWeys
That may be, but it's gonna be harder logistically to do a study commencing
from onset of symptoms vs at moment of hospitalization.

There's also the fact that study makes it less likely that pre-hospitalization
HCQ will have any effect either. Applying a Bayesian analysis here, it's now
likelier that the true ground truth is simply that HCQ doesn't do anything to
COVID-19 at all, not necessarily that it works only in a narrow early window.
HCQ has severe side effects too, that require close monitoring and can be
fatal. If it's not clearly doing good then it definitely shouldn't be being
given to COVID-19 patients.

Personally, my hopes are more on remdesivir and favipiravir, both of which are
actual antivirals (HCQ is not) and thus were always more promising. HCQ was
never the most promising drug candidate, and the only reason we're even
talking about it as much as we are is that, for whatever random reason, that's
the one Trump heard about first and then fixated on.

~~~
Symmetry
The study that made me think there might be something to it was looking at
people taking it for unrelated illnesses and finding that they weren't tending
to show up hospitalized with Covid-19.

I'd agree that we really don't have any evidence that giving it to
hospitalized patients helps at all. Most antivirals have to be taken at the
early stages of an infection.

The best looking treatment for people seriously ill with Covid-19 right now
seems to be IL-6 inhibitors. That won't stop you from getting sick but might
let you avoid intubation.

~~~
ModernMech
This could be correlation. People taking HCQ have autoimmune problems like
lupus, and therefore would be more cautious and practicing social distancing
earlier, therefore not getting infected in the first place. It also might be
true that people who are agoraphobic shut ins are not contracting covid. But
that doesn't tell us much about how covid interacts with agoraphobia.

------
pdonis
A useful compilation of information on HCQ and COVID-19:

[https://docs.google.com/document/d/1O6Cls-
Oz2ZAgJuyDbnICEGjM...](https://docs.google.com/document/d/1O6Cls-
Oz2ZAgJuyDbnICEGjMvQPEyM-aaXARUomR9Ww/edit)

------
Khelavaster
This study is basically garbage. It applies to people who're so damaged from
Covid they need at least 2 liters of oxygen per minute. It studies treatment
with pure hydroxychloroquine--no zinc, no azithromycin/doxycycline/ivermectin.
Hydroxychloroquine.

Patients who get their treatment from doctors less fraudulent than the authors
of this study almost certainly see better outcomes.

------
firasd
When the Covid crisis is over, one of the strangest sub- plots will have been
the fracas around Hydroxychloroquine. Starting from medical practitioners
worldwide adopting its usage in a ‘cargo cult’ way, mimicking what other
doctors were doing, to Raoult’s low- quality study. Then people in Silicon
Valley (notably Elon Musk) picking up the idea. Followed by the explosion in
the political sphere, from Trump pushing it at the White House podium, to
Indian PM Modi reversing an HCQ export ban for Trump, to French PM Macron
talking it up.

All the while HCQ remained unproven for Covid use, while people trying it got
hurt by cardiac side- effects (and one couple in a prominent incident
mistakenly took different chemicals with a similar name), and patients with
other conditions ran out of HCQ due to shortages.

Maybe HCQ will be part of the standard of care for Covid- 19 in the future,
but it’s seeming less and less likely. Meanwhile it’s definitely not a miracle
cure, so the frenzied advocacy and adoption of this medicine will turn out to
have been a bizarre story.

(I wrote this up here
[https://twitter.com/firasd/status/1250125344469708801](https://twitter.com/firasd/status/1250125344469708801))

~~~
massaman_yams
Politically, yes, there was/is a cargo cult. Both for those convinced it's a
cure, and the anti-cargo-cult opposing party convinced it's somewhere between
useless and actively harmful.

From a medical practice standpoint, you have a widely-available drug with
well-known side effects that can be administered in a medical setting with low
risk, and potential life-saving upside. When the research is early but
potentially promising, it's not irrational to administer in cases where the
side effects should be well-tolerated, even if later research shows no or low
benefit.

The problem arises from self-administration without medical supervision, or
with inadequate medical supervision.

~~~
firasd
The problem with 'low risk / high upside' is that it can apply to anything. We
can try lemonade since it has low risk and high upside. But at some point we
have to start wondering if we should all be obsessed with lemonade right?

Even when doctors were using HCQ before the politicians and random outsiders
picked up on it, there were other drugs in the mix that they were also
considering (Lopinavir, Remdesivir, etc). Incidentally Remdesivir trials have
also come out lately seeming pretty weak. But there is still nowhere near the
level of frenzy around Remdesivir as there has been around HCQ to the extent
of advocacy at White House press briefings, international diplomatic
incidents... it's beginning to seem like a very strange mass hallucination.

~~~
bluGill
If there is a serious suggestion that lemonade works we should try it in
medical settings. So far the only suggestions come from those who point to
alternate theories without any science - even a case study. If you get a
doctor to try it and it works ill be more interested. Until then it is quacks
and I'm not.

------
sheinsheish
I don’t understand who gets to decide and how, which of these people receive /
don’t receive a specific treatment. I’ve always loved medical studies, but now
the crisis got me to thinking about the moral decision (playing god?)

~~~
CydeWeys
The answer is, by and large, doctors. Within the hospitals they really do have
the power of life and death, deciding who gets treatment when supplies are
thin. Generally the decisions are made using the heuristic of "With this
limited stock of X, who should we give it to to save the maximum possible
number and quality of lives?"

It's not playing god, it's just making rational decisions in times of
scarcity. That's something humans do constantly, no god necessary.

------
pcj-github
Aside from these results, what is the proposed mechanism of benefit here?

And why are we expecting a mechanism with hydroxychloroquine against this
virus when essentially no small molecule therapies are effective against
viruses in general?

~~~
mcguire
Hydroxychloroquine is an immune suppressant and may help reduce the cytokine
storm effect. How that interacts with the "you have to start it early" issue
is unclear to me.

And it might keep you from getting malaria while you have COVID19.

~~~
thepangolino
The way HCQ is by accumulating in cells. It inhibits the replication of
viruses by interfering with endosome/lysosome trafficking or viral protein
maturation during virion maturation. (basically stops the virus from
replicating)

~~~
chasd00
and, correct me if i'm wrong, zinc helps

take it with a grain of salt but [https://www.snopes.com/fact-
check/zelenko-669-coronavirus-pa...](https://www.snopes.com/fact-
check/zelenko-669-coronavirus-patients/)

~~~
souprock
With the right grain of salt, you get zinc. Suggestions: zinc acetate, zinc
chloride, zinc citrate

------
thanatropism
There are dozens upon dozens of speculative treatments. Interactome research
is churning out candidates.

I think the people have a right to know about cloroquine, since it became such
a political point. But n=181 is not that small.

------
th3829
That's because it's not hydroxychloroquine that helps them. It's Zinc. It just
allows for much better absorption of the Zinc. Same can be achieved by
combining Quercetin and Zinc.

------
projektfu
I know this study doesn’t put anything to bed, but one has to understand that
the basis for the HCQ and CQ (+/\- zinc) thing is the same as x kills cancer
in vitro. Then, you get a motivated researcher who publishes a single arm
study of essentially OK patients claiming zero deaths. Game changer? We’ll
see. But I imagine there are hospitals that are already using this as a first
line treatment and there’s no positive reviews from the front line.

Beyond that, we do have the ability to perform small sample studies (cf.
Student) and decide whether we’re headed in the right direction. Are we in a
lull in statistics where we can’t even use statistics to guide future
research?

------
rurcliped
See also
[https://news.ycombinator.com/item?id=22851998](https://news.ycombinator.com/item?id=22851998)

------
Cantbekhan
TLDR: French publication, non randomized 181 patients (hospitalized with
pneumonia and O2 requirement) with control group (84 with HCQ, 97 without
HCQ), no efficacy but adverse effects for some.

~~~
orblivion
If this is accurate, perhaps the title could be edited to reflect the fact
that it's a single study?

~~~
prox
It is, but these studies are done in a european setting, so more results may
be coming.

------
giardini
full title "No evidence of clinical efficacy of hydroxychloroquine in patients
hospitalised for COVID-19 infection and requiring oxygen:..."

from the article:

 _" We used data collected from routine care of all adults in 4 French
hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min
to emulate a target trial aimed at assessing the effectiveness of HCQ at 600
mg/day...

This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ
within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group).

The median age of patients was 60 years ..."_

 _"...[Patients were from] four French tertiary care centres providing care to
patients with COVID-19 pneumonia. Adult patients were eligible in this study
if they were aged between 18 years and 80 years, had PCR-confirmed SARS-CoV-2
infection, and required oxygen by mask or nasal prongs (corresponding to a WHO
progression score of 5)."_

 _" Among the 181 patients eligible for analysis, 84 received HCQ within 48
hours of admission and 97 did not (although 8 of them did receive HCQ later
on)."_

So, first of all, these patients were infected with Covid-19 _days_ prior and
now had progressed to pneumonia. The up to two-day delay in the administration
of HCQ after admittance to the study is disheartening.

I am surprised that, despite the experimentors selecting an elderly,
pneumonic, oxygen-dependent cohort in advanced stages of the disease, these
patients did as well as they did. Its a credit to the human body.

But timing is everything...

Once a Covid-19 patient has developed pneumonia, it is too late for
hydroxychloroquine to affect the Covid-19 virus' replication process
significantly. The patient's body is saturated with the virus.

In a patient who has developed pneumonia the disease has progressed to a
second phase wherein the virus _and other opportunistic pathogens (e.g.,
bacteria)_ attack the lungs and other tissue. Antibiotics may help at this
point. But it is quite clear that the patients in this study arrived too late
to gain any benefit from hydroxychloroquine which, when coupled with zinc
sulfate, slows or halts viral replication _early_ in the disease, delays or
halts the virus' progress and allows the body time to develop an immunological
response to the virus.

The study's conclusion states explicitly that " These results ... do not
support the use of HCQ in patients hospitalised for a documented SARS-CoV-2
pneumonia."

So, the trick is to treat _early_ with HCQ+zinc sulfate+azithromycin.

------
cheese4242
400+ points on Hackernews for... this?

There have been a variety of studies and reports, both for and against, the
use of hydroxychloroquine. Is there any reason this particular study is so
highly upvoted? Or is this just an attempt to dunk on Trump for suggesting the
drug showed promise?

~~~
tigershark
It’s a study with a fairly high number of participants and it has not been
conducted by the controversial author of the flawed first study.

------
droithomme
Hm, the pseudo-study (it was a after the fact data review) found a near
halving of mortality rates in the HCQ group. Yet that is described as no
evidence of efficacy. Odd.

------
Techies4Trump
Sample size is far too small.

If anything this study shows (albeit with small numbers) that HCQ doesn't make
things worse.

But I have a feeling HCQ will be found to be effective. Big pharma have a lot
of $$$ to make from their vaccine though.

------
krn320
There is an obvious pushback on hydroxychloroquine. Not enough money to be
made so other "solutions" are preferred. Something that was used for more than
50 years is being tested for safety? What a joke. I'm sure when vaccines
arrive they'll be "safe and effective" and used all around the world from day
one...

------
krn320
There is an obvious pushback for hydroxychloroquine. Something that was used
for more than 50 years should've been widely adopted by now but there is not
enough money to be made (and let's not forget political issues). I'm sure when
vaccine arrives it'll be "safe and effective" and widely used around the world
from day one - no questions asked.

------
DevKoala
The sample was 185 patients. There are anecdotal evidences that support the
medicine which claim to have more, the letter came from a French doctor too.
The study is discouraging for sure though.

------
drummer
Instead high doses of vitamin C have proven to be very effective.

------
twomoretime
It _really_ bothers me how hard both citizens and officials seem to be wanting
Chloroquine to fail all because somebody they didn't like endorsed it
publicly. Can't let him have that win, right? Like children.

The original studies that showed promise used combinations of Chloroquine,
Azithromycin, and or zinc, and there is a speculated pathway by which these
drugs interact to interfere with COVID replication. This study only looked at
HCQ.

This kind of partisan, childlike pettiness is dangerous to all of us - what if
Chloroquine works but we overlooked it because a couple shitty papers told us
what we wanted to hear?

Was it appropriate to tweet about? Debatable. It is a presidents job to keep
his people hopeful when possible, and this drug cocktail was in multiple
(admittedly not perfect) papers at the time of the tweet. People need to be
more objective when evaluating statements made by the president. That doesn't
mean you have to like him.

~~~
nkozyra
I think there's a bunch of strawmen here. It's disingenuous to say that people
who found [said person]'s comments to be a bad idea _want it to fail_.

Indeed, if that person had come up and said "there's a lot of promising
treatments, such as ..." or "the experts are telling us that some studies
involving [x, y, z] are showing some positive signs" or something of that ilk,
nobody would have cared. Instead, the person multiple times touted something
that is to date unproved. People find that irresponsible for a number of
reasons, not least of which that there are legitimate users who need this and
it's now in short supply.

So what people are protesting is someone not waiting for medical science and
just causing noise.

Like many things, this person could have handled this all more responsibly.

~~~
twomoretime
>[https://youtu.be/oWQjWepaDv0](https://youtu.be/oWQjWepaDv0)

"Very promising early results".

>[https://www.google.com/search?q=trump+tweet+chloroquine&prmd...](https://www.google.com/search?q=trump+tweet+chloroquine&prmd=insv&source=lnms&tbm=isch&sa=X&ved=2ahUKEwjvzOjehOvoAhVICc0KHcxyD8gQ_AUoAXoECAwQAQ&biw=412&bih=556&dpr=2.63#imgrc=sU_DAlax8JfVaM)

"Have a real chance to be one of the biggest game changers"

Meanwhile the media response has been universally lamenting that a president
would "tell people" [he didn't] to take this drug. How many outlets jumped on
the single chloroquine phosphate overdose as proof of the president's
responsibility? I encourage you to search "Trump" and "chloroquine" and find
me _a single headline_ that doesn't tear into Trump.

Like most people, your views have been warped by headlines and op-eds being
touted as "news."

The fact that the president acts like a child doesn't mean our news should
too. The petty editorialization of the daily briefings are an excellent
example - the media's job in such a case is to be an objective first source -
not to force their point of view through adversarial headlines that change
every 5 seconds and "fact checking" only his alleged untruths. But this is
where the majority of Americans get their news. It's shameful.

Edit: hell, look at this absolutely _ridiculous_ headline at the top of the
CNN "fact check" page: "Fact check: Trump denies saying another thing he said
and makes more false claims at coronavirus briefing"

What kind of headline is that? Is anyone competent left at CNN? The media no
longer deserves the soft power it wields. They lost that privilege when they
strayed so far from any semblance of objectivity.

~~~
Goronmon
_" Have a real chance to be one of the biggest game changers"_

and

 _" Hopefully both will be used immediately. PEOPLE ARE DYING, MOVE FAST"_

Both seem pretty ridiculous when we don't even know if its effective at all,
let alone "one of the biggest game changers".

~~~
twomoretime
There were multiple papers out of Europe and China by then. This was already
floating around before Trump latched onto it because it was indeed promising,
which is exactly what Trump said.

What else do you think the words "hopefully" and "real chance" are here to
communicate?

What do you think "move fast" means? Administer the cure to everyone, or
figure out if it works?

This was a clearly promising avenue and as the head of the executive this is
one of the few things that the man has done right. This vitriol is pure,
irrational bias.

~~~
nkozyra
It's neither vitriol nor irrational to expect a leader to yield to experts and
to relay only reliable information.

What he did instead lacked context or information necessary to mass
communicate. There's a way to communicate it and it wasn't this.

~~~
twomoretime
>it's neither vitriol nor irrational to expect a leader to yield to experts
and to relay only reliable information.

And you want to tell me that from his tweet you already know he didn't get
this information from so called experts? How exactly does this tweet indicate
otherwise?

>What he did instead lacked context or information necessary to mass
communicate. There's a way to communicate it and it wasn't this

Welcome to the new normal, where politicians communicate via tweet. I agree
that it is inappropriate but this particular example is just being used to
project the usual anger onto him with multiple plausible but ultimately
inappropriate rationalizations. There was, again, nothing inappropriate about
a passing mention of a safe, cheap, promising drug. He could have done the
same in the middle of a speech for similar effect.

Besides, what did you expect him to do, cite the relevant studies on Twitter?
Sure, ideally he would, but let's not pretend that more than, say, .01 percent
of the population is even capable of reading studies...

This is a shitty hill to die on.

~~~
nkozyra
> And you want to tell me that from his tweet you already know he didn't get
> this information from so called experts?

Given his experts wouldn't validate it after ... yeah, probably.

> I agree that it is inappropriate but

Then what's the argument here? We both agree it's inappropriate. Just as I do
when any other politician misuses it.

> Besides, what did you expect him to do, cite the relevant studies on
> Twitter?

No. I'd expect him to wait until there's something worth disseminating.

> This is a shitty hill to die on.

Who's dying on what hill here?

------
m0zg
Wow, several HCQ stories on the front page. Means it's probably going to be
proven effective soon.

------
jackfoxy
Totally out of my depth here. I've been following Dr. Chris Martenson's daily
covid-19 updates since late January. He is adamant this treatment is only
effective in combination with zinc supplements.

~~~
supercanuck
So why doesn't this guy setup clinical trials instead of providing non-
confirmed medical advice on the daily?

Probably cause he is lazy and more interested in selling and promoting himself
than he is actually solving problems.

This guy knows the scientific method, I assume. he knows that something needs
to be observable and replicated. Instead, he is asking us to trust his
brilliance on something where the side effect might be death and blindness??

------
mcguire
While we're here,

"Traditional Chinese Medicine in the Treatment of Patients Infected with
2019-New Coronavirus (SARS-CoV-2): A Review and Perspective"
([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098036/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098036/))

Hey, it can't hurt and it might help. China has had one of the best recoveries
from the pandemic.

~~~
perardi
I cannot tell if you are purposefully trolling, or this is sincere.

Regardless, let's wade in…

1\. That's not's a study. That's not a metareview. That's a puff piece by
people who have a strong, strong self-interest in promoting TCM, because they
want to keep their department chairs.

2\. Oh heck, I'll just quote the entire last paragraph:

"The safety of TCM in the treatment of emerging coronavirus diseases was not
included in the observation on SARS patients. It was reported that some herbs
used in TCM contain nephrotoxins and mutagens, while the toxicological
features of the most of Chinese herbal medicines remain to be fully
understood. Furthermore, herbs used in TCM can mimic, or magnify, or oppose
the effect of conventional medicines. Thus, the safety of TCM used in
treatment of emerging coronavirus infections should be carefully evaluated. It
is particularly important to avoid toxicity or interfere with the efficacy of
conventional treatment caused by herb-drug interaction."

So, in conclusion, we don't know if this works, and this stuff may be toxic,
and it may have drug interactions, and oh by the way there's no quality
control on this so you have no idea what's in the medications.

Might as well recommend acupuncture and getting your chakras aligned, couldn't
hurt! (Probably less of a chance it hurting than taking a wild dose of
unregulated herbal supplements.)

~~~
mcguire
" _Might as well recommend acupuncture and getting your chakras aligned,
couldn 't hurt!_"

Indeed, it might help and it couldn't hurt.

" _(Probably less of a chance it hurting than taking a wild dose of
unregulated herbal supplements.)_ "

Or possibly a known drug with no real evidence of efficacy and a long list of
known side effects?

Oh, and by the way, " _That 's a puff piece by people who have a strong,
strong self-interest in promoting TCM, because they want to keep their
department chairs,_" is both an hominem and describes all academic
publications.

------
edoo
What a joke. An emulated trial only in patients already requiring oxygen. How
about this [http://covexit.com/professor-didier-raoult-releases-the-
resu...](http://covexit.com/professor-didier-raoult-releases-the-results-of-a-
new-hydroxychloroquine-treatment-study-on-1061-patients/)

I'm taking the HQZ cocktail at first diagnosis even if I have to doctor shop.

------
hartator
> documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a
> target trial aimed at assessing the effectiveness of HCQ at 600 mg/day

Well hydroxychoroquine is only useful before ventilators are needed (it
attacks the full lungs) and is actually detrimental - we know that - after by
its nature.

What kind of bad science is this study where you actually push patients
through a known dangerous path to try to prove the non efficiency of a
potential treatment.

~~~
ejstronge
>Well hydroxychoroquine is only useful before ventilators are needed (it
attacks the full lungs) and is actually detrimental - we know that - after by
its nature.

I’m worried that this has totally left the realm of science and is just pure
politics... there is no evidence for a ‘magic window’ for HCQ in COVID-19
treatment, or any solid evidence of a positive role.

Secondly, having supplemental oxygen is _not_ the same as being on a
ventilator. I imagine most hospitalized COVID patients need oxygen (otherwise,
they could be managed at home).

I hope we all avoid making comments (or even accepting comments) about
medicine without either critical, independent study or background knowledge.

