Covid: Remdesivir 'has little or no effect' on survival, says WHO
bbc.co.uk
bbc.co.uk
https://blogs.sciencemag.org/pipeline/archives/2020/10/09/ha...
> The good news is that the patients receiving the drug had a shorter time to recovery (9 to 11 days, in the 95% confidence interval, versus 13 to 18 days with non-remdesivir standard of care. That’s real, but it’s not real dramatic, either, which is what you would realistically expect from a single broad-spectrum antiviral drug. This ain’t sofosbuvir clearing out hepatitis C, and even that one doesn’t do the job by itself. As for the hardest endpoint of all, mortality by Day 29 for these patients was 11.4% with remdesivir therapy as compared to 15.2% with the controls. So again, that’s a real improvement and very much worth having, but it’s not a Miracle Drug, either. Adverse events were actually lower in the treatment group, which is of course good news.
Just so everyone knows, this is the same guy that writes the 'Things I Won't Work With" blog. It's all about insane chemical compounds and is very much one of the best blogs ever written.
https://blogs.sciencemag.org/pipeline/?s=things+I+won%27t+wo...
Shame about the liver and kidneys though.
(Not trying to be a jerk, but based on your anecdata, it's equally likely that remdesevir/dex/twinkie would really help as well; We know dex makes a huge difference from several well done tests. The question is whether remdesivier and twinkie have any effect, indepedently or in combination)
With that being said, anti-virals often only work well when given very early (sometimes even as a preventative) and right now from looking at this study it doesn't seem like this was done. So this study may only be confirming what we already know about how anti-virals should be used (at a very early stage) but it will hopefully have the good effect of stopping improper usage.
Based on what I've seen discussed, ending trials early is a fairly common (though admittedly contentious) practice in medical RCTs when you're dealing with very serious illnesses, especially when there are no alternative effective treatments[1].
The issue is that there is a tradeoff between an abundance of caution to procure conclusive results and giving patients access to medicine which "clearly helps". In an ideal world you would run every RCT for several years to figure out any possible long term effects and accurately determine efficacy, but there are many circumstances where you could argue doing so (if it's clear the medicine works during the early stages of the trial) is more unethical than giving people medicine which shows some promise to work.
But it should be noted that such trials are still solid science (the trial was an RCT), it just means you cannot take them as evidence of long-term efficacy.
[1]: https://www.ahajournals.org/doi/full/10.1161/circheartfailur...
A question to you and grandparent post: what are the things that distinguish a high quality RCT from a poor one? The number of participants, the design study, etc.? Any links/resources that discuss this would be appreciated.
edit: ok, I found a paper on this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429837/#:~:tex....
I am super curious now about any discussion that reveals why the WHO study was less-than-stellar, and why the original RCT was considered high-quality.
Typically you'd register a "stopping rule" before you start your trial: a good drug often will trigger the stopping rule, as it helped so much that we learned about its efficacy on a smaller N than originally planned.
There are many different stopping criteria, depending on the trial (in safety trials you'd typically stop because you've found evidence that the drug is unsafe and continuing would be unfair to the folks in the treatment group, whereas in efficacy trials after safety has been established, you'd stop because you've found evidence that the drug is effective and continuing would be unfair to the folks in the control group).
in fact there is a downside risk to continuing as well, further study might show that the early results were an outlier and the drug is not as effective as previously thought (or has some serious side effects in some situation), and then you lose all the money you've invested. But if you push it through, there is no risk of being sued since the US Government has waived any liability on the part of drug companies for these therapies.
in a game-theoretic sense there is absolutely no benefit to continuing the trials and potential downsides to doing so. Remember, for-profit companies don't care about maximizing public health, they care about maximizing revenue. Especially when you've explicitly removed all financial liability for being risky with public health.
I don't think the science is solid when a trial can pick from 2nd-tier endpoints and stop the trial once an improvement is found. It is quite possible that if the trial had gone on longer the one positive effect would be reduced or even go away entirely or that we would see a negative effect in a more important endpoint.
Steady-state, sure, you can treat 25% more.
Of course it's disappointing to see it may not be as effective as we previously thought. And of course analysis may yet reveal issues with either one or the other or both studies. That's how science works - facts, not heartfelt desires.
Perhaps we are talking about different things? I was addressing the current COVID-19 pandemic.
It's $3k a patient. The five days difference in hospital stay that was implied costs a lot more than that, even if there is no mortality/morbidity benefit, and that's ignoring that we were worried about running out of hospital capacity.
Secondary endpoints, decisions about when to end trials, etc, are all fraught with peril.
It's worth noting that neither SIMPLE nor the ACTT-1 Remdesivir studies moved from a mortality to a non-mortality endpoint. SIMPLE did have an endpoint change before any data was available, but it was a relatively minor, innocuous thing.
> The primary efficacy end point was clinical status assessed on day 14 on a 7-point ordinal scale consisting of the following categories: 1, death; 2, hospitalized, receiving invasive mechanical ventilation or ECMO; 3, hospitalized, receiving noninvasive ventilation or high-flow oxygen devices; 4, hospitalized, requiring low-flow supplemental oxygen; 5, hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to Covid-19); 6, hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol for remdesivir administration); and 7, not hospitalized (see Table S1 in the Supplementary Appendix, available at NEJM.org).
In case of COVID, it's not just a cost issue, but also clearing the bed as soon as possible, to put a new patient in.
10% less hospital stay, means 10% more patients able to get help.
> ... and that's ignoring that we were worried about running out of hospital capacity.
Anyways--
> 10% less hospital stay, means 10% more patients able to get help.
This isn't true. It's only true at steady state, but if there's an exponential process you get a smaller benefit. (E.g. take the ridiculous case that 100% of patients show up on one day-- obviously a shorter stay doesn't improve the number you treat in that case).
It's just worth noting that you get significantly less than a 1/.9 benefit in capacity when you shorten hospitalization times by 10%. It's a benefit, but it's only this ideal value when things are perfectly steady state. So sorry for the pedantry, but "10% less hospital stay, means 10% more patients able to get help."--- it's not the predicted 11% or even 10%.
What's balancing against that is continuing the trial means giving patients a placebo when you have evidence of a better treatment.
It's a really complex issue both scientifically and ethically.
But even then, more participants and more time for follow-ups is generally better all other things being equal (which they never are).
When 2 days ago Orban announced from nothing that they will provide Remdesivir to everyone, I knew that again they did something stupid...I want the experimental drug that Trump got, not some leftover drug with lots of side effects.
Now I know that it was not Orban who was screwed, but the whole EU.
My point about it being solid science is not that it is a good (from a scientific perspective) to end trials early, merely that the early part of the trial was still an RCT and the data is just as solid as any other RCT which ran for the same period of time. From what I've seen, this is a contentious topic in academia because the ethics of this make it harder to argue that RCTs should always be run to completion (with no exceptions).
But any good RCT will have a stopping criteria established before the trial starts to eliminate ex-post-facto cherry-picking. I'm not familiar with the exact details of the Remdesivir trial and whether they had a reasonable stopping criteria defined beforehand -- I was speaking more broadly about the topic of ending RCTs early.
When using other clinical endpoints cherry-picking is to be avoided. [1]
> For a trial to stop early for benefit, the observed effect on the composite end point ideally should be consistent in the individual components.
[1] https://www.ahajournals.org/doi/full/10.1161/circheartfailur...
It showed no evidence for the strong benefit they were looking for (mortality), but a similar trial started in China before that trial, ended - and showed no change in mortality, but some shortening of the hospital stay (even though that wasn't its stated hypothesis). At that point, the western RCT remdesivir trial added the "hospital stay" target, and lo-and-behold, shortly afterwards, it turned out that it does result in no less mortality but shorter hospital stay as well.
While it does give some credence to the "shorter hospital stay" result -- having reached it in to Gilead initiated RCTs -- It was statistically significant but not dramatic;
And now another trial says even that's not so significant.
However, Gilead apparently received the WHO study on 28 September and so were aware of the conclusions of the study before they signed a deal with the EU Commission.
This naturally leads to further questions, as discussed in this tweet thread:
https://twitter.com/kakape/status/1317042940825436162
Edit: Martin Landray, professor of medicine and epidemiology at the University of Oxford and leader of the UK-based Recovery trial also has a good summary of the WHO trial:
https://twitter.com/MartinLandray/status/1316989951297396736
But the effect is modest at best - and so far there is no strong evidence it is there at all."
But it doesn't follow at all that because there is no effect when administered late, the effect, if administered early, is modest as best. In fact, there are many medication that are very effective if administered before the first symptoms appear and are completely useless after. If you get exposed to rabies, you can get a rabies vaccine and have close to no chance of contracting it, whereas if you get a vaccine after you develop symptoms, you're almost certain to die.
Similarly, the flu antivirals are somewhat helpful if taken early but have no effect if taken too late.
"...Remdesevir is given by intravenous infusion for 5-10 days. It is not cheap. And supplies are limited (not surprising given scale of epidemic)."
This means anyone showing early symptoms is likely to require a stay in hospital for early administration of the intravenous infusion. There are questions about how scalable this is. Landray again:
"COVID affects millions of people & their families around the world. It is not a rare disease and we need scalable, affordable, and equitable treatment solutions."
>So, unless you die, if it cut hospital time, it would improve survival.
The drug may have some negative effect on the chance that you'll die each day, but it is unlikely that the effect would be strong enough to prefer spending more time in critical condition. And getting cured faster will allow your immune system to be more able to fight off other risks.
Maybe that's what usually happens. It's not hard for me to imagine that it could improve survival for some, but has fatal side effects for some percentage. The numbers could be arranged so that survival doesn't change but average hospital stay is lower. Is this the case? Probably not, but I have no idea.
Edit: The closest Gilead has come to suggesting a survival advantage from Remdesivir was a comparative analysis presented in July [1]. The analysis was highlighted as inconclusive because it wasn’t a double-blinded placebo-controlled study, which is the gold standard for clinical trials.
[1]: https://www.bloomberg.com/news/articles/2020-07-10/gilead-s-...
The problem is that since it's intravenous, it's hard to justify giving it to people BEFORE they seem sick.
Naturally patients and doctors are pressured to treat the sickest patients first, and so they get the Remdesivir, despite it likely not doing much so late in sickness.
Ideally, if we could identify people highest at risk, and early in their disease - THEY should be given the drug very rapidly. ...but again, without that identification step, it's very hard to justify giving someone an experimental treatment.
One the one hand you could say: WHO has an unreviewed study that says "china early vaccine tests good, usa drug bad" and Gilead has a bunch of studies that say usa drug good.
On the other hand you could say: the studies wording is so fine tune that its hard to say if any are true.
Results:
- some side with their political/religious beliefs (and will downvote this probably)
- some are confused about what is true and admit they just don't know (I'm definitely there)
- some are a bit of both
That's the scope of the authorized investigatory use in the US, so unless you think the Trump Administration is simultaneously promoting and sabotaging it, I think it's the intended target:
“VEKLURY® (remdesivir) is authorized for use under an EUA only for the treatment of adult and pediatric patients hospitalized with suspected or laboratory-confirmed COVID-19, and for whom use of an intravenous (IV) agent is clinically appropriate. VEKLURY must be administered via IV infusion.”
https://www.remdesivir.com/us/?gclsrc=aw.ds&&gclid=CjwKCAjwi...
The way I see it, hospitalized can mean: I have great insurance and I went into the hospital for treatment because I felt some symptoms. I was feeling 80% well when I went in, I was only there because the doctors wanted to be thorough and check my vitals overnight.
It can also mean: I don't have insurance and I waited until I was half past dead to go to the hospital because I have bad/no insurance. By the time I got to the hospital I couldn't even breath. I went straight to the ICU.
Both are 'hospitalized'. But I don't think the two examples represent the same reality. I'd imagine Remdesivir working very well on the first and not very well on the second due to viral load concerns mentioned in other parts of the commentary to this article.
But it’s not clear to me that the WHO has any credibility left.
Edit:
This is not a coded American Politics statement. Here are examples of where the WHO provided directly counterproductive recommendations:
1. Don’t wear masks (https://www.google.com/amp/s/amp.cnn.com/cnn/2020/03/30/worl...)
2. Don’t close borders (https://www.reuters.com/article/us-china-health-who/who-says...)
3. COVID is not airborne (https://m.facebook.com/WHO/posts/3019704278074935) (pedantic takes aside you should obviously treat it is if it were)
When I remember back on the news about the other recent pandemic scares (ebola, swine flu, zika), I don't remember hearing any mention of the WHO. I'm sure it happened, but not nearly as much as CDC. We hear about their announcements a lot more often now, but how much is that due to being cast as antagonists by DC?
I'm now leaning more toward my hypothesis that they haven't changed behavior much, but US reporters are citing them now because the current administration brought them into the story. In the past, reporters probably read the WHO announcements but quoted from CDC same academic experts. Again, WHO info is dry.
On Jan 14, 2020, the WHO had no clear evidence of human-to-human transmission yet. It came (to them) shortly afterwards.
That China may have had such evidence and kept it private doesn't make the WHO's statement any less truthful at the time it was issued. They aren't an intelligence organization; they rely on cooperative member nations.
https://www.factcheck.org/2020/04/factchecking-trumps-attack...
> While there is a debate about what was known when — and it seems clear that China knew more than what it reported — the WHO never said the virus was not communicable. Instead, the agency always considered the possibility, even if it also shared information from China that found no evidence of such transmission.
> Lack of evidence, especially of “preliminary” results, does not mean the WHO was saying the novel coronavirus could not be spread between people. The same day as the tweet, the WHO cautioned that there might be some human-to-human transmission of the virus among family members in China.
> According to a timeline of events, Van Kerkhove, who is also the WHO’s technical lead for the COVID-19 response, also said that human-to-human transmission wouldn’t be unexpected, since that is what occurs with SARS and MERS, which are also coronaviruses.
Just a few days later:
> By Jan. 19, the WHO was more definitive, saying in a tweet that there was “some limited human-to-human transmission occurring between close contacts.”
Trying to use this tweet to justify US inaction months later is silly and transparent.
1. It was spreading rapidly in humans
2. It was a coronavirus and therefore was similar to other coronaviruses
If you were following a precautionary principle, you’d have said “it likely is spreading between humans given we’ve never seen any other form of transmission this rapid in any virus that isn’t, and it’s a coronavirus”.
If you think their “don’t wear masks” lie was ok because it was trying to keep medical workers from a shortage, then, how can you not see this as hypocritical? You can’t think the mask lie was ok, due to abundance of caution, and then a total disregard for caution at a much more crucial early stage as ok.
But again, if you were paying attention, watching the WHO make statements like this was terrifying. Like driving in a car with a drunk driver who is stepping on the gas. Who in their right mind would make such a totally braindead, reckless press release like that. Technically there’s no direct evidence, but there’s a whole lot of reason to be worried it likely is airborne. So the headline should be “it’s highly possible it’s airborne, we are waiting for concrete data, but recommend caution given exponential spread within humans”.
The WHO did things similarly shockingly bad three times or so during the pandemic. I was paying attention to all of them and couldn’t help but think something was up. Something was wrong with the WHO. Not just being conservative, but being totally negligent and backwards time and time again. It really seems they were playing either protection for China, or some sort of interference against a good chunk of the world.
If they had done better, many many lives would have been saved. It was some internal politics that broke them. Any halfway sane person knew it at the time.
As the excerpts I've cited demonstrate, the WHO's statements at the time are longer than what can be fit in a single 280 character tweet. The tweet is accurate; the WHO was also issuing far more detailed statements including cautions about exactly what you assumed at the time - that further information was likely to arrive later.
Again:
> According to a timeline of events, Van Kerkhove, who is also the WHO’s technical lead for the COVID-19 response, also said that human-to-human transmission wouldn’t be unexpected, since that is what occurs with SARS and MERS, which are also coronaviruses.
They were making the exact point you claim they didn't make.
> International traffic: no restrictions recommended. Wuhan city is a major domestic and international transport hub. Currently, there are no reports of cases outside of Wuhan City. Given the heavy population movements, expected to significantly increase during the Chinese New Year in the last week of January, the risk of cases being reported form elsewhere is increased. WHO does not recommend any specific health measures for travellers. It is generally considered that entry screening offers little benefit, while requiring considerable resources. In case of symptoms suggestive to respiratory illness before, during or after travel, the travellers are encouraged to seek medical attention and share travel history with their health care provider. WHO advises against the application of any travel or trade restrictions on China based on the information currently available on this event.
It’s a good thing Trump didn’t listen to them and limited immigration by end of January. They made many more reckless recommendations like this well after they knew people were dying, it was spreading rapidly, and it was a coronavirus.
https://www.washingtonpost.com/outlook/2020/10/01/debate-ear...
> The measure that the Trump administration implemented could not be described as a “ban” that “closed the country”: It only prohibited U.S. entry to foreign nationals who had visited China in the last 14 days. Americans and U.S. permanent residents returning from Hubei Province were still allowed, subject to a 14-day quarantine. After these policies were enacted, hundreds of thousands of travelers continued to arrive in the United States via direct flights from China. Until Feb. 27, no other travelers to the United States faced such travel restrictions and quarantine requirements — even if they were arriving from other nations that were reporting coronavirus cases.
> Restricting flights from China did nothing to prevent the virus from arriving from other parts of the world. Genetic analyses have shown that the large epidemic that unfolded in New York was linked to travelers from Europe. In the early days of the U.S. epidemic, testing was restricted to people with a travel history to China, which limited the ability to detect locally the cases and infections among travelers from other countries.
> By the time Trump expanded travel restrictions to Iran on Feb. 28 and to European nations on March 12, it was largely too late. By mid-March, the United States was approaching 2,000 confirmed cases and experiencing severe shortages in testing capacity that meant many infections likely went undiagnosed. The travel restriction did not initially apply to the United Kingdom, which already had hundreds of reported cases. And, implementation caused chaos. Photos showing large crowds of Americans stranded together in long lines and tight corridors for hours at airports may have increased virus transmission among those travelers who eventually made their way back to the United States.
https://apnews.com/article/0dc271ad7f7917374a5a0cfb49273783
> A recent study from the journal Science found China’s internal crackdown modestly delayed the spread of the virus. It cast doubt that travel restrictions elsewhere will do much compared with other preventive measures, citing in part the likelihood that a large number of people exposed to the virus had already been traveling internationally without being detected.
I personally know someone coming here from China who was disallowed end of January.
That he didn’t go all the way and ban US nationals is only because that would have probably been untenable politically and legally.
Travel restrictions absolutely prevent spread to argue against that shows fundamentally you’re willing to make silly arguments to win, I won’t engage further.
Saying "The WHO did things similarly shockingly bad three times or so during the pandemic" and then pivoting to praise Trump on his COVID handling is pretty hilarious.
Editing here as I can’t reply. I’m not debating on failure vs success in the US in this thread, you seem to be caught up in that. I’m simply completely refuting that the WHO was even close to doing well.
Here’s a decent summary of multiple mistakes and pandering to China: https://foreignpolicy.com/2020/04/02/china-coronavirus-who-h...
The WHO themselves even said they made a “huge mistake”. So I guess you’re out there on your own in defending them.
But more than that, anyone paying attention saw they were in China’s pocket. You’re grossly misinformed.
What's your definition of failing?
We didn’t even do that properly - American citizens were allowed to return, weren’t screened, and were asked to observe a “voluntary” quarantine.
We wound up mostly getting it from Europe, where we similarly didn’t restrict until it was far too late.
You’ve been fooled by fake news. Just google and you’ll find the truth. Here’s an article from February 2 “All over the world, countries are imposing travel bans on visitors who’ve been to China“ https://qz.com/1795615/coronavirus-travel-bans-on-china-impo...
So it’s the exact opposite of what you said - politicians all over the world were doing just that.
According to a later analysis at https://www.politifact.com/factchecks/2020/apr/13/joe-biden/...
“ By the group’s count, Biden is correct about 45 nations restricting travel from China before the United States.That number covers variations of travel restrictions in effect up to and including Feb. 1.”
First, US closed late Jan before they are citing many others than closed right after that, I know someone who was disallowed before the 31st but they wouldn’t be straightforward on why, so the admin was restricting travel even before the announcement.
And I was referring mostly to within the US there, and with the WHO. Here’s Biden right after the ban:
> We need to lead the way with science -- not Donald Trump's record of hysteria, xenophobia and fear-mongering.
And before you reply saying he didn’t mean directly at the ban, I don’t buy it. It was sent directly after the announcement specifically saying “xenophobic” and suggesting the alternative was “science”. That isn’t someone who is signaling they support it.
This leads some credence to the theory that the various restrictions on travel were, and continue to be more politically, than medically motivated.
"No evidence" is falsely interpreted by the layperson as evidence of absence, or at least that there isn't a good reason to expect it to be true. But given the asymmetric costs involved, it is exactly the wrong assumption that people need to make.
Assume there is airborne transmission -> low cost but hedge extreme downside risk.
Assume there is no airborne transmission -> slightly lower cost, but huge downside risk if incorrect.
Policymakers were misled by the WHO.
> Policymakers were misled by the WHO.
Man, if only "policy makers" had access to "scientific circles" so they could stop getting their public health pandemic response ideas from reading Twitter.
That's only ~10% of the reason that people are critical of the WHO though. They also refused to declare a pandemic until until weeks after it had spread globally, even though early R estimates were around 3, which delayed countries' ability to respond quickly. They wouldn't recommend masks until months into the pandemic, even though similar viruses such as SARS were airborne.
The list of heinous mistakes is laundry-list long.
One week later, the WHO had already conducted its own field visit in Wuhan and concluded that human-to-human transmission is likely taking place [1].
[1] https://www.who.int/china/news/detail/22-01-2020-field-visit...
https://www.reuters.com/article/us-china-health-who-idUSKBN1...
But, I did read recently about polio eradication from the African continent etc. Obviously not just by WHO but efforts by many organizations, but still a major achievement isnt it?
Update: I actually would like to know why WHO is not credible any more for some. Honest question.
The original plan that the WHO and the rest of the global health community came up to deal with this also seems like total magical thinking to me - basically, everywhere would drop the type 2 poliovirus component (which corresponded to a virus whose wild type had been eliminated) from their live vaccines at once, which would leave none to turn into vaccine-derived poliovirus and type 2 woud just go away. It didn't work that way. I can't fathom why it even should. Nonetheless, there were lots of fancy documents and presentations from the WHO and other such organisations explaining this strategy very hopefully. The current ones don't have the same level of hope.
I can fathom this easily. The general idea is to administer the type 2 oral vaccine (along with 1 and 3, but we’re talking about type 2 here) widely enough that you expect a high level of herd immunity. Specifically, you want sufficient immunity that any newly introduced cases of reverted-to-virulent type 2 will quickly die out. (If you have the resources, you also try to give almost everyone the injectable vaccine to prevent virulent type 2 cases from causing damage). Then you stop giving the type 2 vaccine. If it works, then type 2 is locally eradicated.
Maybe it’s “magical”, but this particular magic has worked in almost the entire world.
At least earlier on the narrative was that "the WHO is in the pocket of China" [1] -- while in reality of course the Americans were a dramatically bigger contributor both financially and politically. Further at the same time, the Chinese were actually threatening the WHO and leadership for not playing ball.
Typical 2020 dumpster fire. And at the end of the day the people really hurt are once again the poor countries who depend on the WHO, and we're left with a pile of sadly misinformed "they have no credibility" armchair quarterbacks. It's always easier to try and tear down a system than understand and fix. That's my opinion anyways.
For a more balanced take I suggest this Atlantic piece [2].
[1] https://www.businessinsider.com/mike-pompeo-who-workd-health...
[2] https://www.theatlantic.com/politics/archive/2020/04/world-h...
This made me laugh out loud
I suppose next time I reply to a contentious topic I could find a more seemingly dispassionate source but these days most folks are too polarized to read any news source that doesn't align with their preconceived notions.
Current WHO head was elected in part thanks to chinese votes and influence. When the WHO recommended not closing any borders, how can you disentangle the professional epidemiology opinion from the political push? You can't.
Which is not to say it is evil or incompetent (it may be either, both, or none - I don't know enough) - but it seems to have an aura of "professional only" organization, which is unjustified.
If your response is "well, that sucks", yes, I agree. It sucks to live in a world where people and institutions whose sole job is supposed to be making sure true information gets to the public, every time, no exceptions, are either unwilling or unable to do that job right.
That's not to say I behave irresponsibly: I wear a mask in public (because "better safe than sorry"), my family self-quarantined for two weeks when one of us got sick, etc. I just don't assume what "experts" say is necessarily the truth. (To be fair, I also don't trust myself to reach correct conclusions—hence my personal policy of "better safe than sorry.")
I personally feel like too much of modern society involves idolizing experts and institutions—after all, it's nothing more than the argument-to-authority logical fallacy (admittedly, even if it's often a useful heuristic)... but that's a discussion for another time :-P
Same here. My wife and I were wearing masks, social distancing, not going to public places like restaurants where there was a high risk of catching something, weeks before any public health authorities were recommending such measures, and before the case rate in our area started to spike. To us it was obvious common sense.
All I'm saying is that, as I see it, society's idea of "science" often conflates it with scientists and/or institutions themselves (hence the "argument to authority" part of my comment above). This is, of course, the opposite of what science means, which is why it bothers me enough to have written these comments :-P
Saying "better safe than sorry" makes it sound as though you're not sure about this, but this one isn't in doubt - masks reduce the spread of the virus, and that's their primary purpose.
Here's an article about it: https://www.ucsf.edu/news/2020/06/417906/still-confused-abou...
See the section titled "What evidence do we have that wearing a mask is effective in preventing COVID-19?"
False. They said - "There is no specific evidence to suggest that the wearing of masks by the mass population has any potential benefit"
"In the community, we do not recommend the use of wearing masks unless you yourself are sick and as a measure to prevent onward spread from you if you are ill"
"The masks that we recommend are for people who are at home and who are sick and for those individuals who are caring for those people who are home that are sick,"
These are completely normal statements.
>2. Don’t close borders
False. The said "There is a “huge reason to keep official border crossings open” to avoid people entering irregularly and going unchecked for symptoms, "
"Certain containment measures will be appropriate, but widely banning travel, closing down cities, and hoarding resources are not realistic solutions for an outbreak that lasts years."
>3. COVID is not airborne
Please understand that airborne has a scientific meaning, and that is the terminology that scientists use. There is no actual clinical evidence of the airborne transmission of COVID.It is spread through large droplets. If it was airborne, those cloth and surgical masks that people wear would be useless, so you might as well not wear them.
--
>But it’s not clear to me that the WHO has any credibility left.
Maybe that is true for you, but ironically your wild accusations have let me wondering about your agenda here. :)
At this point, it's expert consensus that airborne transmission of COVID is a significant if not the major route of transmission[1].
https://www.pnas.org/content/117/26/14857
> If it was airborne, those cloth and surgical masks that people wear would be useless, so you might as well not wear them.
Not quite useless, but nowhere near as effective as people would like to believe them to be.
I read dozens of studies every day as part of my job in biotech, and most papers are junk and/or contain overly enthusiastic claims that few can replicate. I know somehow on HN linking to a paper is seen as a mic-drop, but that is not the case in the real world.
If the model evidence-based, falsifiable, and tested, applying modeling to a set of conditions is a way of deriving evidence-based conclusions about the likely outcome of those conditions.
No, it's a way to derive evidence based hypotheses. A model that does not include a confounding variable (of which there are many) cannot give any conclusion about that variable - at most a hypotheses.
I've spent some time looking at the models, all of them fail - some spectacularly so (those that inform policy much more so, unfortunately). To the point of being useless, I might say, because their stated assumptions usually apply almost everywhere, but their prediction (and back testing results) match only a small sample (e.g. a few specific countries or cities).
The source is for the "if not majority" part of that sentence. The other part is just me making an admittedly unsubstantiated claim.
https://www.nytimes.com/2020/07/04/health/239-experts-with-o...
> I know somehow on HN linking to a paper is seen as a mic-drop, but that is not the case in the real world.
Sure, but this is HN. You often have to source stuff just to not get downvoted.
"The evidence is admittedly incomplete for all the steps in COVID-19 microdroplet transmission, but it is similarly incomplete for the large droplet and fomite modes of transmission. The airborne transmission mechanism operates in parallel with the large droplet and fomite routes [16] that are now the basis of guidance."
By using arbitrarily high standards for evidence, I might as well claim there's no evidence that COVID is transmitted by large droplets or by smear infection. Where's the randomized trial that proves beyond any doubt that coughing in each other's faces will spread COVID?
I'm kind of surprised that there isn't much of a discussion about that, because if it is indeed a significant route (say 30%), all the masks and distancing in the world won't help until this is also addressed.
https://www.nature.com/articles/d41586-019-01726-1
Edit: downvoted for stating facts and linking to a Nature article? I guess HN has a soft spot for peddlers of pseudoscience and rhino boner pills as long as it their side politically.
https://www.nature.com/articles/d41586-018-06782-7
This is where I draw the line.
https://www.nature.com/articles/d41586-018-06782-7
Please don’t twist yourself batting for this nonsense.
Can you please paste the relevant quote from the article? Because I'm not seeing that. The part I looked at was:
"In a statement on 4 April, it insisted that the TCM chapter does not discuss particular remedies. Rather, it is meant to give doctors the chance to diagnose patients using both TCM and Western medicine — what it calls “optional dual coding”. These categories “do not refer to — or endorse — any form of treatment”, the statement says."
Let's also not forget that they refused to declare a pandemic until weeks after there was evidence of global spread.
The negligence (intentional or otherwise) is truly shocking.
"We need to be clear. The world is facing a significant shortage of PPE for our frontline workers -- including masks and gloves and gowns and face shields -- and protecting our health care workers must be the top priority for use of this PPE."
That's very World Health Organization, which is used to operating under scarcity.
The embarrassing thing now is that, eight months on, we don't have a huge supply of N95 masks, which actually protect the wearer. On eBay, the price is starting to drop, from about $10 each to about $5 each. Normal price is about $1 each.
(Emphasis mine)
To give an analogy, I can take painkillers to suppress pain but my body is still as sick as before - it "only" affects my perception. Now, I'm not against easing symptoms in itself but given how many people I know who go to work while coughing I don't know how to feel about medication that only helps with perceived discomfort.
(then again, I'm in Sweden where barely anyone seems to take covid seriously, sadly)
> In a trial in China over February–March 2020, remdesivir was not effective in reducing the time for improvement from COVID‑19 or deaths, and caused various adverse effects, requiring the investigators to terminate the trial. [1]
> On 17 March 2020, Didier Raoult announced in an online video that a trial involving 24 patients from southeast France supported the claim that hydroxychloroquine and azithromycin were effective in treating for COVID-19.[0]
> On 18 March 2020, the World Health Organization (WHO) announced the launch of a trial that would include one group treated with remdesivir. [1]
> As of April 2020, remdesivir was viewed as the most promising treatment for COVID‑19... [1]
---
[0]: https://en.wikipedia.org/wiki/Hydroxychloroquine#COVID-19
And multipled it by the sum of the numbers from those dates??
No? Me neither.
He implies some conspiracy is at play, rather people desperately trying to draw conclusions or gain 5 min of fame.
When you do gematria, you're asserting the importance of a pattern you've discovered without seeking how common the pattern actually is (which turns out to be pretty damn common in instances where the pattern doesn't have any implication). You're basically doing the same thing when you cherry-pick three events to support a conclusion in a context when there are many events you could choose from.
82 69 77 68 69 83 73 86 73 82 are the ASCII values of "remdesivir". For each of those, replace it by the sum of its digits, and keep doing that until each becomes a single digits: 1 6 5 5 6 2 1 5 1 1.
Take those in pairs, 16 55 62 15 11, and do the same kind of reduction to single digits: 7 1 8 6 2, to get 71862 is Remdesivir symbolic number.
What does that tell us about Remdesivir?
Well, add 24 to it - the answer to the ultimate question of life, written backwards. The result is 71886.
Write the number backwards, subtract 1960 - the year first contraceptive pills hit the market. The value is now 66857.
Write the number backwards, subtract 1989 - the year of the Exxon Valdez spill. The value is now 73877.
Subtract 13 - the symbol of bad luck. This gives you 73864.
Flip the number backwards, then divide by 7 - the number of deadly sins and the symbol of magic. The outcome is 6691.
This number, written backwards, spells 1966 - the year Anthon LaVey founded the Church of Satan.
Clearly, we should avoid Remdesivir.
But wait, I hear you say. Why did I use ASCII values? Maybe I should use 18 5 13 4 5 19 9 22 9 18, which are the positions of the letters in the alphabet. That would give 58649 as the Remdesivir symbol.
OK, fine. But that still ties Remdesivir to Satan:
Write the number backwards, add 2 - the symbol of duality. The number is now 94687.
Add 4991 to it - the year Jeffrey Dahmer died in prison, written backwards. The result is 99678.
Add 61 to it - the atomic number of sulfur, written backwards. The result is 99739.
Write the number backwards, subtract 125 - the only number known that contains all its proper divisors as proper substrings. The value is now 93674.
Divide by 14 - the number of pieces Osiris was torn into in Egyptian mythology. The result is 6691.
This number, written backwards, spells 1966 - the year Anthon LaVey founded the Church of Satan.
QED
The above courtesy of one of the best sites on the net: https://lcamtuf.coredump.cx/evilfinder/ef.cgi?said=Remdesivi...
You can hit refresh there and it will give different numerical connections of Remdesivir to evil.
These companies possess the means to influence the news media through their advertising spend, and the agencies through regulatory capture. The timeline also strongly suggests that this is what happened, as Remdesivir came into the spotlight exactly one day after the other protocol was announced.
No conspiracy theories. Conspiracy theories allege some kind of criminal activity and there is no crime being alleged. All it takes is one person to send a press release.
You haven't come out and said it explicitly (despite being asked), so I'll say it explicitly and let you contradict me: You are a hydroxychloroquine truther. For some reason you believe it must be effective although there is no useful evidence for that either.
Interestingly, the site also seems to list Remdesivir as possibly useful, somewhat weakening your not-a-conspiracy-theory-just-pointing-out-"interesting"-observations.
Also, the site made the country data at https://c19study.com/countries.html more respectable-looking since the last time I saw it, but the data quality still seems to be crap. In Central Europe the Czech Republic sticks out as dark green "widely used", but none of the sources linked allow this conclusion.
https://www.historyofvaccines.org/content/blog/vaccine-rando...
For those unfamiliar: Derek Lowe is a drug discovery chemist who writes a well-known blog on drug discovery and other chemical topics (most notably the "Things I Won't Work With" series, which covers nasty chemicals like ClF₃ or C₂N₁₄), which has of course been dominated by COVID-19 in 2020.
That remdesivir was publicly considered a leading candidate after its supposed proof-of-failure and before the HCQ treatment was publicized rather demolishes whatever implication of conspiracy is being considered.
Even if HCQ is useless, that doesn't preclude the notion that it was seen as a threat to Big Pharma's bottom line in mid-March. Of course it was. Like I said earlier, it's cheap and out-of-patent.
I think all of us in this thread are circling around the same understanding when it comes to the facts of the matter. But where we differ is that I'm much more open to the idea that the authorities could have self-serving motives in play besides keeping us safe. The idea that policymakers and even scientists may be corrupt is not far-fetched. We have to try to keep an eye on them. Have a great day and thanks for the debate.
> By Selina Koch, Executive Editor | Feb 27, 2020 | 7:56 PM EST > Editor's note: Updated on Mar 17, 2020 at 9:30 PM EDT
March 17th again. I'd love to know what edit was made at 9:30 PM on the same day the HCQ announcement came out. The Wayback Machine didn't find anything.
And Derek Lowe's summary was unchanged in his edit:
> My personal opinion is that I like the chances of this drug [remdesivir] more than anything else on this list, but it’s still unlikely to be a game-changer.
> My personal opinion is that I like the chances of this drug more than anything else on this list, but it’s still unlikely to be a game-changer.
The interpretation section states
“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.”
Later on it states “ No patients were enrolled after March 12, because of the control of the outbreak in Wuhan and on the basis of the termination criteria specified in the protocol, the data safety and monitoring board recommended that the study be terminated and data analysed on March 29.“
So that study which you are touting as proving remdesivir didn’t work was stated by its own authors to require a larger study. (China was so successful at suppressing the coronavirus using quarantine and isolation that they ran out of people to test on pretty early on during COVID as well, resulting in a low sample size for studies)
The trial is small (100 participants), so we should be doing a larger one now, but I don't think there is a down-side to adopting this as a standard of care.
[1] https://www.sciencedirect.com/science/article/pii/S096007602...
Also, why don't the governments just distribute elderly and weak vitamin D and zinc to take everyday? There's not much harm that can be done with those and could potentially offset lack of sunlight that might have kept COVID-19 in check during the summer. A low-risk low-cost solution that could potentially yield enormous health and economic benefits if the link between vitamin D and zinc deficiency on the severe outcome of COVID-19 is proved later.
So it’s really a no-win situation because if you give it early, not many people will look like they’re getting better relative to control. But if you give it too late to those who have severe symptoms it will be too late.
What they need to do is figure out a way to identify who will get severe symptoms and give remdesivir to them early. That’s probably the only way you will see a benefit, If there’s even a benefit at all.
I thought that was some interesting food for thought there.
https://www.statnews.com/2020/04/23/data-on-gileads-remdesiv...
It just wasn’t as effective as antibody treatments so got shelved in favor of them.
By the way, there is a supplement that is far far cheaper than remdesivir and is available over the counter which has also shown to reduce time to recovery by about as much as remdesivir. See:
https://investors.chromadex.com/news/news-details/2020/Chrom...
This is a 100 person trial, which is much less than the remdisivir trials, but still statistically significant. In any event, the risk is much lower, according to the study "adverse events were uncommon, benign, and self-limiting." The supplement is sold as truniagen.
But looking at the real data, the study was not completely randomized as they had removed some patients. Patients that had died.
So it was essentially a P-hack to sell us a worthless but expensive product. So I stopped believing that Big Pharma would save us, and that their science-journals were giving honest reports.
In the mean time I see reports of different very cheap medicines that give a 10x reduction in death-rates. From 500 to 50 and such. That is extremely hard to hack because these death numbers would show up elsewhere. From the reports it appears that the virus is very vulnerable to some cheap anti-viral medicine.
But there is no money in that, so it will not be promoted that heavily.
Here are some videos where the science papers are explained by an expert.
https://www.youtube.com/watch?v=2uzXHnUViro&feature=emb_logo
Now I want to see more information, as he points out the early trails used to dismiss it used a dangerously high doses.
He is a nursing teacher and his videos basically take up to date research and news on covid as he explains it to a non technical audience. Personally I rally appreciate that he takes the time filter out what appears to be interesting / important and presents it in a way that is easy for the general public to understand.
If you still can't be bothered to do that then the paper he is discussing is here (I assume that a peer reviewed paper is up to your high standards) but you will be missing out on a lot of information about dosages that John adds: https://doi.org/10.1016/j.ijantimicag.2020.106144
>I said in February, I will say it again
Repetition doesn't make your argument any more valid.
The available capacity is quite low. The media is saying there will be 1m treatments for US for next year, and 500k for whole EU.
Which leads to an awkward situation: the availability right now probably only justifies to offer this drug to more severely ill patients, to whom this drug probably makes less impact anyway.
Hydrochloroquine seems to have been dismissed, but watching this video he makes a a good case for it working at low dose - it seems like a lot of the trials involved too high a dose. (He talks about a relatively large scale study in Belgian hospitals).
There seems to have been multiple studies done, some giving good results some not. I am curious if the ones at the lower dosage were separated out would they all gave more positive results. Unfortunately I don't have time to check through them all myself.
https://www.youtube.com/watch?v=2uzXHnUViro&feature=emb_logo