
Remdesivir in adults with severe Covid-19: random, double-blind, placebo trial - garraeth
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext
======
refurb
Punchline - _" Although not statistically significant, patients receiving
remdesivir had a numerically faster time to clinical improvement than those
receiving placebo among patients with symptom duration of 10 days or less
(hazard ratio 1·52 [0·95–2·43])."_

That said, this morning Gilead reported that in their own pivotal trial that
the drug met it's primary endpoint.[1] What we don't know is how big of an
effect it was.

[1][https://endpts.com/gilead-pivotal-covid-19-study-of-
remdesiv...](https://endpts.com/gilead-pivotal-covid-19-study-of-remdesivir-
met-its-primary-endpoint/)

~~~
air7
Any line that starts with "Although not statistically significant" should be
automatically deleted.

~~~
downerending
In general, yes. In an emergency when there are no other obvious better
alternatives at hand, looking at results with relatively poor p-values might
still be a pretty reasonable thing to do.

~~~
jakeogh
also
[https://news.ycombinator.com/item?id=23013667](https://news.ycombinator.com/item?id=23013667)

------
cthalupa
Not an expert, not a doctor, etc.

My barely informed interpretation and resulting take here is that:

1) This really only shows any efficacy when given shortly after the onset of
symptoms

2) Remdesivir is an expensive and IV only drug that is difficult to produce in
high quantities

3) The combination of the above makes this not particularly useful for
treating the general population - we do not want everyone that shows mild
symptoms to be rushing to the doctor for a treatment that has to be provided
by a professional, and by the time we know if the symptoms will be severe and
life threatening it is too late for remdesivir to be useful

4) That would seem to make it most useful for people that have known risk
factors and co-morbidities to be candidates for remdesivir use. I do not know
if the results are similarly promising for people that have those criteria,
however.

If these results hold up it's good news, but I don't know if it's great news -
it seems like the factors involved here make it impractical for the large
scale treatment of cv19

------
lowdest
From a nurse in Wuhan who is a family friend: It seemed clear to her and her
coworkers that Remdesivir was working when given early, but had little or no
effect after the disease had progressed.

My take: sounds like great news for a product, since everyone would want this
on hand to catch infections early. Unfortunately it is an IV treatment and
very difficult to manufacture, and is therefore unlikely to be able to fill
that role. I bought a few shares anyway.

~~~
yonaguska
Isn't that effectively the same result with hydroxychloroquine + z-paks?

~~~
DylanBohlender
Sounds like it (I've also heard of zinc being added in with HCQ and the z-pak
as part of that treatment protocol, sometimes called the "Raoult protocol" and
referred to hereafter as such for brevity).

Both the Raoult protocol and remdesivir appear to help if used earlier in the
disease progression; neither seem to do anything if the disease has progressed
past a certain point.

If early use is the key to efficacy (and if both demonstrate the same degree
of efficacy, as it seems currently), the Raoult protocol is the only one that
makes sense to scale up. The ingredients for the Raoult protocol are much more
easily mass-produced and administered, whereas remdesivir is proprietary, very
expensive, and IV-only (as other posters have noted).

------
isoprophlex
Notwithstanding its effectiveness... I'm not sure if this could quickly be
produced on a large scale.

For those versed in organic chemistry: looks pretty complicated. Maybe someone
with industry experience can guess how difficult this is to productionize on a
global scale?

[https://en.m.wikipedia.org/wiki/File:Synthesis_of_Remdesivir...](https://en.m.wikipedia.org/wiki/File:Synthesis_of_Remdesivir.png)

~~~
luizfzs
Yeah, from this article, it's pretty complicated and with very low yield

[https://www.acsh.org/news/2020/03/26/problem-remdesivir-
maki...](https://www.acsh.org/news/2020/03/26/problem-remdesivir-making-
it-14665)

------
buboard
This is an older study which IIRC terminated early because they couldn’t
rectuit enough ppl.

There is newer, positive data coming out today from the ongoing study of
advanced covid: [https://www.niaid.nih.gov/news-events/nih-clinical-trial-
sho...](https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-
remdesivir-accelerates-recovery-advanced-covid-19)

------
blakesterz
I honestly do not understand what the interpretation means:

"In this study of adult patients admitted to hospital for severe COVID-19,
remdesivir was not associated with statistically significant clinical
benefits. However, the numerical reduction in time to clinical improvement in
those treated earlier requires confirmation in larger studies."

~~~
lnanek2
It means it didn't help people who already had severe symptoms, but might help
people if it is given to them earlier.

This is actually quite well known when treating the flu with anti-virals. My
doctor has said in previous years, if I wake up with full body ache and feel
like it's the flu, come in immediately and he'll prescribe anti-virals. He
said if I wait, there's no point, though.

Makes sense the anti-virals might only be enough to stop viral replication if
given early on before it's all over the place.

~~~
glaugh
And while neither effect was found to be stat sig, the “treat earlier” group
was _close_ to stat sig (eyeballing it, it probably would have been stat sig
at 90% confidence) so that’s good enough reason to try again with a larger
sample size. If the effect stayed roughly similar, a larger N would lead to a
smaller confidence interval that would not include a non-effect if an odds
ratio of 1, and therefore be stat sig evidence of benefit.

Edit: Also it looks like they didn’t find an effect overall, but if they slice
the data to just those who were treated early, they’re _closer_ to having
something stat sig. Hopefully that was a pre-planned cut of the data, but
either way the interpretation is still probably “Somewhat promising but needs
more data.”

------
jfoster
It sounds like the patients in the study were a bit far into the illness
already. Maybe lots of damage is already done and they are just having to
additionally cope with the side-effects of the drug and not getting much of
the benefit due to it having been started too late.

~~~
KingOfCoders
Interesting points, did you read the study? Have they adressed those points?

~~~
jfoster
I haven't read the full study, so I don't know whether those have been
addressed, but judging from the summary, it may not have been a consideration.
I've heard of a few other studies recently where this was completely
overlooked; they pick patients who are the most severe and give them the
drugs.

Antiviral drugs won't reverse damage that's already done.

------
drderidder
Nobody seems to be talking much about favipiravir, which seems a bit like not-
invented-here syndrome. If it stood to make a lot of money for some US big
pharma company I suspect we'd be hearing more about it.

~~~
newacct583
It seems to me like people "talking much about" unproven drugs is the
_problem_ , and that favipiravir (and its patients) is lucky to have been
spared much of that nonsense.

People want to talk about this stuff because it feels like a magic bullet.
Viral infections don't have magic bullets[1], they just don't. We have to beat
this with elbow great: huge amounts of testing and tracing once the outbreak
is at a manageable baseline, and high uptake of mitigation strategies like
social distancing until it gets there. And yes, that costs a lot of money.

[1] Rather: they do, but they're called vaccines and take time.

~~~
HarryHirsch
_Viral infections don 't have magic bullets_

They do. Consider HIV/AIDS. Nowadays, someone who gets HIV-positive at the age
of 20 can expect to live to 70. It's quite astounding what modern combination
therapy can do.

~~~
frank2
And the current treatments for hepatitis C have mild side effects and usually
eradicate the infection even if the infection has been going on for 20 years.

------
lykr0n
It's ... something. and that's better then what we had.

~~~
SiempreViernes
Actually, the result is that making pills out of sugar and writing Remdesivir
on the box is likely the better treatment.

~~~
orwin
we don't know yet. it might hasten the recovery speed, and have not been
tested with early patients.

------
eli_gottlieb
Ok, excuse me for just complaining, but this study setup seems... bad.

That is, I believe the prior indication was fairly low to null that antiviral
drugs would significantly help the treatment of a severe respiratory infection
-- in the first place. You don't give someone Tamiflu when they have a
sufficiently severe flu pneumonia and fever to be hospitalized, do you?

Antivirals are usually indicated for treatment when an infection is still in
its early, mild, pre-hospitalization stages. I understand that it's easier to
recruit study subjects with severe COVID-19 than mild at this stage, but
still, doesn't this study amount to looking for one's keys under the lamp-post
because it's brighter there?

------
bpodgursky
Lots of legitimate questions about statistical significance, but it's strong
enough that Fauci likes it[1], which tells me it can't all be bunk (given how
cautious he's been about *quine):

> White House health advisor Dr. Anthony Fauci said Wednesday that data from a
> coronavirus drug trial testing Gilead Sciences’ antiviral drug remdesivir
> showed “quite good news” and sets a new standard of care for Covid-19
> patients.

> Speaking to reporters from the White House, Fauci said he was told data from
> the trial showed a “clear cut positive effect in diminishing time to
> recover.”

[1] [https://www.cnbc.com/2020/04/29/dr-anthony-fauci-says-
data-f...](https://www.cnbc.com/2020/04/29/dr-anthony-fauci-says-data-from-
remdesivir-coronavirus-drug-trial-shows-quite-good-news.html)

~~~
usaar333
That's from a more powered US trial, not the one in China. The argument is
that Giliad basically got "unlucky" with this China one (insignificant number
of patients/deaths to nullify hypothesis Remdesivir does work)

~~~
khuey
The Chinese trial got aborted early due to lack of patients as I understand it
so that's not that surprising.

It also means this isn't any sort of "miracle" drug though.

~~~
lbeltrame
Nevertheless, it is a drug that has shown some positive efficacy in a real
trial (the NIH one, I mean). IMO this is a significant step forward.

I hope other viable treatments emerge from the other trials on drugs set to
close by June.

