
Early treatment of Covid-19 with HCQ and AZ:retrospective analysis of 1061 cases - sandGorgon
https://www.sciencedirect.com/science/article/pii/S1477893920302179
======
narrator
HCQ is also used in Costa Rica[1] for every patient and they have a very low
death rate[2]. It's interesting that since it's such a cheap widely available
drug, and even produced locally in Costa Rica, that developing countries can
use it for every case.

[1][https://qcostarica.com/hydroxychloroquine-the-drug-costa-
ric...](https://qcostarica.com/hydroxychloroquine-the-drug-costa-rica-uses-
successfully-to-fight-covid-19/)

[2] [https://www.worldometers.info/coronavirus/country/costa-
rica...](https://www.worldometers.info/coronavirus/country/costa-rica/)

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klmadfejno
As far as I can tell, this is not a controlled study, but just an analysis of
a bunch of people who took the drugs at a pretty low dosage. The analysis
doesn't (and couldn't) make any conclusions about HCQ improving patient
outcomes vs. not using HCQ; but rather just tries to assert that it didn't
make things worse and we should therefore do it because China says it's a good
idea. Without any baseline it's not clear to me how one could evaluate these
claims. Sounds just about as useful as the previous paper.

As an aside, I do feel like the mean age of poor clinical outcomes, 69, feels
a bit low relative to my expectations.

~~~
forgot_user1234
> any conclusions about HCQ

did you read this "A total of 1061 patients were included in this analysis
(46.4% male, mean age 43.6 years – range 14–95 years). Good clinical outcome
and virological cure were obtained in 973 patients within 10 days (91.7%). "

> l, this is not a controlled study,

You can retrospectively get the control data for same time frame. This won't
br same as placebo but still good.

AND, death rate in france for closed cases is around - 15-25% .

Death rate with HCQ+AZ is 0.75%

If I got crona. I will take the HCQ+AZ

~~~
akiselev
_> You can retrospectively get the control data for same time frame. This
won't br same as placebo but still good._

No you can't and no it won't. Clinical study protocol documents are often
thousands of pages long because they need to describe mundane procedures down
to how doctors and nurses are supposed to draw the subjects' blood so that
there aren't significant variations between participating hospitals. The point
of a control group is to control as many variables as possible and placebos
are only a small part of that. Selecting control groups is an entire subfield
of modern medicine.

Many drugs with much more promising early results that were gathered under
nearly ideal conditions (instead of the chaos of a pandemic) have failed hard
in third phase trials.

~~~
zeku
You actually can. I'm a Software Engineer/Data Scientist whatever--and this is
a part of my job.

You can take the entire case cohort and filter out all of the people who we
don't have robust data for. Then find a control cohort who do have all of the
things we're looking at and then analyze the data. Yes it would've been better
to do a grade A trial from the get go, but these kinds of studies can be done.

~~~
akiselev
I've actually worked on clinical trials. Most of the industry has been moving
towards _preregistering_ clinical trials so that statistical analyses like the
one above can't be used to demonstrate efficacy by using retroactive patient
selection criteria that only keeps the most favorable data points (like this
paper does, in effect).

I'm not arguing with the validity of the statistics, I'm saying it's not
enough to fulfill the medical standards for demonstrating drug efficacy. An
actual clinical trial protocol needs to be properly designed and coordinated
across participating facilities - otherwise it's simply garbage in, garbage
out, no matter the quality of the statistical method.

Edit: The exception is cases like this where the drug is approved for some
uses and doctors in some countries are legally allowed to prescribe it off
label using their own judgement of statistical analyses like the one above.
However, the issue becomes liability and most doctors will fall back to FDA
recommendations that are based on controlled clinical trials.

~~~
zeku
Yeah, I agree you need a full up to standard clinical trial to really get
something like this into the US medical system under normal circumstances.

I was just mentioning that things can be learned from this study
retrospectively by creating a control group from an EHR.

It has validity in the short term for MD's who might begin using this
treatment under our fast track system we're using for COVID stuff.

If this trial was done at my institution and my team already had all of the
paperwork out of the way with regards to the data access we could have
something useful in a week or two out the door. So I hope this will be done by
someone somewhere, just to save lives in short term.

~~~
akiselev
My apologies, I misunderstood your previous reply. I'm just afraid that
loosening standards in this specific crisis is walking a really fine line. It
makes sense during short burn epidemics like ebola where the fatality rate is
so skewed, but exposing millions of people to HCQ during an extended highly
infectious pandemic, especially without proper screening, is dangerous. Small
price to pay if we're talking about something safe like aspirin or if HCQ cuts
the CFR in half but if it's only a 10-20% difference, or the effect disappears
with a larger sample size, or the mad rush for the drug causes a breakdown in
quality control, or the demand deprives people who need it for other reasons -
there's a very high chance of worsening quality of life for many people and
creating a net negative.

What is the fast track system for COVID? I've seen the emergency use
authorizations for clinical testing but not any for new treatments other than
the usual off label use.

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lbeltrame
Note: this is from Didier Raoult's group, the one who published a rather
controversial study on a very limited number of patients last month.

I just skimmed through the paper, but what attracted my eye is the mention of
severity at admission being a risk factor (but the confidence intervals are
_huge_ so I don't know what to make of it).

~~~
godelzilla
The dishonesty of this group is manifest in the quote:

"Finally, a retrospective analysis of data from patients hospitalized with
confirmed SARS-CoV-2 infection in all United States Veterans Health
Administration medical centers found no evidence that, before ventilation, the
use of HCQ either with or without AZ, reduced the need for subsequent
mechanical ventilation"

Compared with what the paper actually says:

"In this study, we found no evidence that use of hydroxychloroquine, either
with or without azithromycin, reduced the risk of mechanical ventilation in
patients hospitalized with Covid-19. __An association of increased overall
mortality was identified in patients treated with hydroxychloroquine alone __.
"

[https://www.medrxiv.org/content/medrxiv/early/2020/04/23/202...](https://www.medrxiv.org/content/medrxiv/early/2020/04/23/2020.04.16.20065920.full.pdf)

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greatgib
Still, no raw/source data provided with the study.

Everyone has to wonder why you would publish results without publication of
the sources when you want to convince people with an important subject...

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steeve
I'm glad HN is not jumping on the HCQ bandwagon blindly, and actively reads
the studies which, unfortunately for all of us, don't show anything.

It is quite disturbing, however, to see on French Twitter, the far right,
complotists, nationalists, and even bots push Raoult so hard...

~~~
lbeltrame
Personally I'm not interested much in what Raoult says or not. The fact that
he might be shady and eccentric does not make the null hypothesis true (nor
the alternative hypothesis, of course).

I'm confident that the COVID-19 PEP trial by U of Minnesota will help put an
end to this polarized debate on the use of HCQ (which for most part has
nothing scientific going on).

~~~
steeve
That was my point. They are pushing Raoult the persona, and are never talking
about the studies.

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newacct583
This is so infuriating. This might work. It might not. Data is still (and must
be, really) still anecdotal. It will be a year or more before high quality
studies are done.

Yet we have to argue about the ?!@#!$ thing repeatedly, because public figures
(we all know who) decided to push this idea irresponsibly as a miracle cure.
So now all the people on one side of the discussion have to crow about every
positive result as if it vindicates the original rhetoric.

It does not. I mean, this might work a little! It might save some lives at the
margin. It's not going to significantly affect the course of the pandemic.
It's just not.

~~~
klmadfejno
> It does not. I mean, this might work a little! It might save some lives at
> the margin. It's not going to significantly affect the course of the
> pandemic. It's just not.

This is a really good take on it for those who aren't into reading scientific
papers. It's totally plausible HCQ does help a bit. If true, it changes
virtually nothing about our current situation. The decision making is all the
same.

~~~
lbeltrame
> If true, it changes virtually nothing about our current situation.

Honest question: why?

(Note: my background includes pharmacology, so I am more interested in
pharmacological options rather than vaccines)

~~~
mlyle
If we end up with a treatment that swings infection fatality rate from 0.6% to
0.55% and reduces hospital stay time by 15%-- and HCQ probably does less than
this-- the public policy choices we'd want to make are basically identical.
Peak hospital load for a wave is lowered by much less than 15%; body count is
just about as bad.

Yes, everyone who has their life saved by this treatment is happy, and it's
worth chasing small improvements on the margin... but...

(It's worth noting that the (very) little evidence from controlled trials that
we have leans more in the direction of harm than benefit, too. But the same
argument holds for e.g. remdesivir where we do have some decent evidence).

~~~
lbeltrame
> If we end up with a treatment that swings infection fatality rate from 0.6%
> to 0.55% and reduces hospital stay time by 15%

Unsure about fatality (the data is a statistically insignificant trend), but
the NIAID trial preliminary data points that remedesivir does cut recovery
time by 30% (11 days vs 14 days) according to their interim report. I have to
dig up the exact definition.

Yes, not HCQ, but data on drugs exist. Too bad it's probably one of the
hardest to manufacture.

~~~
mlyle
OK, but this has nothing to do with what I said.

Even cutting recovery time by 22% doesn't lower peak ICU usage very much--
less than 22% because there's still the effect of the exponential peak.

The point is it doesn't affect policy / the fundamentals of the situation in
any way. It's something that individual patients are happy and thankful for,
but the overall societal situation is the same. A treatment that reduced the
chance of ending up in ICU by 50% would, but this isn't enough to move the
needle.

