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Remdesivir: Gilead wins with unimpressive results announced by press release

On Wednesday, Dr. Anthony Fauci announced positive results for the antiviral drug remdesivir treating COVID-19. They were unimpressive and, suspiciously, announced by press release rather than scientific paper. It’s all very fishy, but one thing’s for sure. Gilead Sciences will make boatloads of money.

I’ve been writing a lot about the unjustified and premature hype over hydroxychloroquine, an anti-malarial drug with mild immunosuppressive activity that is also used to treat rheumatoid arthritis and other autoimmune diseases and how the drug probably doesn’t work against COVID-19, despite its being hyped by President Trump and his sycophants, toadies, and lackeys on Fox News, Dr. Mehmet Oz, Dr. Phil, Dr. Didier Raoult, and a bevy of irresponsible fame seeking doctors who have no idea how to do a proper clinical study. There are, however, other drugs being hyped out there, drugs that might actually have a better chance of turning out to be effective treatments for COVID-19. Chief among these is remdesivir, the experimental antiviral drug being tested by Gilead Sciences. Remdesivir is an adenosine (a nucleotide) analog that inhibits viral RNA polymerases. It is incorporated into RNA made by the virus, causing the premature termination of the RNA molecule, thus interfering with viral replication. The drug was originally developed to treat Ebola and Marburg but was ultimately found to be ineffective against these viruses. Because it inhibits the replication of a number of RNA viruses, it was only natural that it would be considered as a possible treatment for COVID-19, and Gilead has been relentlessly promoting it as such as the company has been working to carry out clinical trials.

What prompted me to write about remdesivir were headlines like Dr. Anthony Fauci says Gilead’s remdesivir will set a new ‘standard of care’ for coronavirus treatment that started popping up on Wednesday afternoon:

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.”

Fauci said the median time of recovery for patients taking the drug was 11 days, compared with 15 days in the placebo group. He said the mortality benefit of remdesivir “has not yet reached statistical significance.”

The results suggested a survival benefit, with a mortality rate of 8% for the group receiving remdesivir versus 11.6% for the placebo group, according to a statement from the National Institutes of Health released later Wednesday.

“This will be the standard of care,” Fauci, director of the National Institute of Allergy and Infectious Diseases, added. “When you know a drug works, you have to let people in the placebo group know so they can take it.”

My skeptical antennae started twitching immediately, because on the same day a study from China was published in The Lancet that was far less impressive. In fact, it was a negative trial. What also got my skeptical antennae all aflutter twitching away was how the results of the remdesivir trial were announced. Normally, when a study is announced to the press, it’s upon publication of the paper, and the press release is issued either the same day or the evening before publication. As of last night, as I wrote this, however, the actual paper reporting the results of the clinical trial had not yet been published. As I perused Twitter on Wednesday, I found even more reasons for skepticism.

So, before I get to the study touted by Dr. Fauci, let’s review some history.

Remdesivir: The early days versus COVID-19 (like, you know, three weeks ago)

The first data published on remdesivir was a single-arm uncontrolled trial that somehow got published three weeks ago in The New England Journal of Medicine. This was peak COVID-19 publishing, when an uncontrolled case series of patients with severe COVID-19 treated with remdesivir under compassionate was published in a super high impact journal like NEJM and made headlines as a result. Be that as it may, the case series examined 61 patients with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing room air or who were receiving oxygen support. They received a 10-day course of remdesivir, consisting of 200 mg given intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. (Remdesivir is an intravenous drug.) The authors reported clinical improvement in 68% of evaluable patients:

Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation.

The case series also did not collect viral load data to confirm potential antiviral activity in humans or any association between declines in viral load and clinical improvement. Basically, when you get right down to it, this study was not really much better than Didier Raoult’s crappy study of his hydroxychloroquine/azithromycin combination, but that didn’t stop the authors from concluding that comparisons with contemporaneous cohorts “suggest that remdesivir may have clinical benefit in patients with severe Covid-19.” In reality, like Raoult’s trials, this trial said nothing about the efficacy of remdesivir against COVID-19 other than that the drug could be given to COVID-19 patients with a reasonable safety profile.

Less than week later, as related by Derek Lowe, came news that two clinical trials of remdesivir in China, one for severe disease and one for moderate disease had been suspended. (They still are.) Lowe noted that both trials had the notice: “The epidemic of COVID-19 has been controlled well at present, no eligible patients can be recruited.” The apparent explanation was “the stringent inclusion criteria for the trials – apparently patients had to have no previous therapy with any other experimental agent to enroll, and that eliminates a lot of people.” Around the same time, Adam Feuerstein and Matthew Herper published a story in STAT, Early peek at data on Gilead coronavirus drug suggests patients are responding to treatment:

The University of Chicago Medicine recruited 125 people with Covid-19 into Gilead’s two Phase 3 clinical trials. Of those people, 113 had severe disease. All the patients have been treated with daily infusions of remdesivir.

“The best news is that most of our patients have already been discharged, which is great. We’ve only had two patients perish,” said Kathleen Mullane, the University of Chicago infectious disease specialist overseeing the remdesivir studies for the hospital.

Her comments were made this week during a video discussion about the trial results with other University of Chicago faculty members. The discussion was recorded and STAT obtained a copy of the video.

Derek Lowe discussed this story in depth, and I largely agree with him that the leak of the video to STAT was a serious breach of clinical trial ethics and protocol. (I’m not alone in suspecting that it was almost certainly intentional to jack up Gilead’s stock price, a result that was achieved.) Lowe also noted:

But now that it’s out there, let’s talk about what’s in the leak. Gilead stock jumped like a spawning salmon in after-market trading on this, and one of the reasons was that that 113 of the 125 patients were classed as having “severe disease”. People ran with the idea that these must have been people on ventilators who were walking out of the hospital, but that is not the case. As AndyBiotech pointed out on Twitter, all you had to do was read the trial’s exclusion criteria: patients were not even admitted into the trial if they were on mechanical ventilation. Some will have moved on to ventilation during the trial, but we don’t know how many (the trial protocol has these in a separate group).

Note also that this trial is open-label; both doctors and patients know who is getting what, and note the really key point: there is no control arm. This is one of the trials mentioned in this post on small-molecule therapies as being the most likely to read out first, but it’s always been clear that the tradeoff for that speed is rigor. The observational paper that was published on remdesivir in the NEJM had no controls either, of course, and that made it hard to interpret. Scratch that, it made it impossible to interpret. It will likely be the same with this trial – the comparison is between a five-day course of remdesivir and a ten-day course, and the primary endpoint is the odds ratio for improvement between the two groups.

Again, these data, such as they are, are no more useful than Didier Raoult’s data on hydroxychloroquine and azithromycin to treat COVID-19, but this brings us to the Chinese trial published in The Lancet on Wednesday.

The Chinese randomized clinical trial

The Chinese trial published two days ago is the first randomized, double-blind, placebo-controlled clinical trial of remdesivir to treat COVID-19, but it was also one of the studies halted. Eligible patients were adults admitted to the hospital with laboratory-confirmed SARS-CoV-2 whose symptoms had lasted less than 12 days before enrollment and who had an oxygen saturation on room air of 94% or less or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less (another measure of hypoxia), and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir at the same dose as the NIH trial touted by Dr. Fauci or the same volume of placebo infusions for 10 days and were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined at the time from randomization to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. An intention-to-treat analysis was carried out.

Basically, this was a negative trial. Of the 255 patients screened, 237 met the eligibility criteria, and 158 were assigned to the remdesivir group, with 79 assigned to placebo control. Unfortunately, remdesivir treatment was not associated with a shorter time to clinical improvement, and mortality was not different between the two groups. Subgroup analysis looking for hypotheses found that there was a trend towards a shorter duration of symptoms (not statistically significant) in patients treated with remdesivir who had had symptoms for less than ten days. Most disappointingly, there was no detectable difference in viral load between the remdesivir groups and the placebo controls. Again, basically this was a negative study with only the barest hint that remdesivir might—I repeat, might—work if administered earlier in the course of COVID-19. That’s some pretty thin gruel.

Which brings us to the NIH trial of remdesivir touted by Anthony Fauci.

The NIH press release for its remdesivir trial.

The results of the NIH remdesivir trial can, unfortunately, only be gleaned from the press release and news stories so far:

For the first time, a major study suggests that an experimental drug works against the new coronavirus, and U.S. government officials said Wednesday that they would work to make it available to appropriate patients as quickly as possible.

In a study of 1,063 patients sick enough to be hospitalized, Gilead Sciences’s remdesivir shortened the time to recovery by 31% — 11 days on average versus 15 days for those just given usual care, officials said. The drug also might be reducing deaths, although that’s not certain from the partial results revealed so far.

“What it has proven is that a drug can block this virus,” the National Institutes of Health’s Dr. Anthony Fauci said.

“This will be the standard of care,” and any other potential treatments will now have to be tested against or in combination with remdesivir, he said.

Here is the press release, posted to the National Institute of Allergy and Infectious Diseases website:

Hospitalized patients with advanced COVID-19 and lung involvement who received remdesivir recovered faster than similar patients who received placebo, according to a preliminary data analysis from a randomized, controlled trial involving 1063 patients, which began on February 21. The trial (known as the Adaptive COVID-19 Treatment Trial, or ACTT), sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is the first clinical trial launched in the United States to evaluate an experimental treatment for COVID-19.

An independent data and safety monitoring board (DSMB) overseeing the trial met on April 27 to review data and shared their interim analysis with the study team. Based upon their review of the data, they noted that remdesivir was better than placebo from the perspective of the primary endpoint, time to recovery, a metric often used in influenza trials. Recovery in this study was defined as being well enough for hospital discharge or returning to normal activity level.

Preliminary results indicate that patients who received remdesivir had a 31% faster time to recovery than those who received placebo (p<0.001). Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo. Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059).

More detailed information about the trial results, including more comprehensive data, will be available in a forthcoming report. As part of the U.S. Food and Drug Administration’s commitment to expediting the development and availability of potential COVID-19 treatments, the agency has been engaged in sustained and ongoing discussions with Gilead Sciences regarding making remdesivir available to patients as quickly as possible, as appropriate. The trial closed to new enrollments on April 19. NIAID will also provide an update on the plans for the ACTT trial moving forward. This trial was an adaptive trial designed to incorporate additional investigative treatments.

As you can see, the difference in mortality was not statistically significantly different, although that could just be because of inadequate numbers. It’s also very important to note the part about the adaptive trial design of this trial, which puts Dr. Fauci’s comment about how remdesivir will become the “standard of care” going forward into the proper context. In this particular trial, multiple different drugs can be compared to placebo or standard of care. The idea is that, if a signal of efficacy is found with one drug, that drug becomes “standard of care” and the trial is adapted to study how adding other experimental drugs compares to the “standard of care.” So what Dr. Fauci meant was that, based on the finding, going forward remdesivir will become the “standard of care” arm for the trial and the experimental arm will become remdesivir plus another experimental therapeutic. However, given that the FDA is on the verge of issuing an emergency use authorization for remdesivir to treat COVID-19, it looks as though remdesivir will become standard-of-care in general soon.

But back to the results. Derek Lowe observed:

… it’s worth noting that had there been “clear and substantial evidence of a treatment difference” during the trial that the DSMB was to have halted the study at that point. We can infer that nothing rose to that level, then: we have a difference, but not substantial enough to have ended the trial prematurely.

It’s also worth noting some things posted on Twitter about the trial. For instance, Waller Gellad noted:

https://twitter.com/walidgellad/status/1255581527972417536

It’s very odd that the primary endpoint was changed:

https://twitter.com/markhoofnagle/status/1255832103071121411?

This long Twitter thread explains:

I’ll summarize, so that you don’t have to scroll through a Twitter thread if you don’t want to. As James Heathers and Waller Gellad noted, the original primary outcome of the trial when it was registered on March 20. The original primary endpoint of the trial was an 8-point severity scale (death, on ventilator, hospitalized with oxygen, all the way down to discharged with no limits on activity) but was changed to time to recovery. There’s still a similar scale for the secondary endpoints, but no numbers for that were reported. (Any bets on whether the results are negative?) This change was apparently made on or around April 16.

Gellad also notes:

https://twitter.com/walidgellad/status/1255857270992273413

It does look very fishy to me. Endpoint or outcome switching, particularly late in a clinical trial is a huge red flag. Don’t get me wrong. There can be legitimate scientific reasons to switch primary endpoints of a trial. as James Heathers puts it:

There are also other reasons to question this trial, including how no confidence intervals were reported, that not even an abstract was published, just a press release with, as Heathers put it, “two results in four lines”:

Basically, if you have two “good” results and twenty “bad” or uninterpretable results, what do you do? What are you going to tell people? The two “good” results, of course!

Gary Schwitzer has a nice summary of the negative reactions to the trial and how it was announced.

The bottom line

I remain very suspicious that the NIH study was announced the same day that a negative study out of China of remdesivir was published. It just seems too…convenient. Maybe I’m being overly suspicious. Maybe I’m too suspicious. Maybe I’m falling prey to conspiracy mongering. However, in the Trump era, when the Trump administration has politicized previously (mostly) apolitical government agencies as never before, it’s hard not to wonder.

Adding to my suspicion is the fact that the study was reported in a press release, rather than being published, which makes me wonder if the press release was written to counter the negative study from China that would certainly have tanked Gilead’s stock prices. Yes, I know that the press release reported that this decis, apparently the announcement was decided upon after April 27 meeting of the data and safety monitoring board overseeing this trial, but the outcome switching so late in the trial makes me very suspicious. Yes, the explanation, which should have been in the press release, along with an acknowledgment that the primary outcome/endpoint had been changed, but wasn’t is not unreasonable:

Then there was this news report in which Fauci claimed that concerns about leaks fueled the announcement:

He expressed concern that leaks of partial information would lead to confusion. Since the White House was not planning a daily virus briefing, Fauci said he was invited to release the news at a news conference with Louisiana Gov. John Bel Edwards(D). “It was purely driven by ethical concerns,” Fauci told Reuters in a telephone interview.

“I would love to wait to present it at a scientific meeting, but it’s just not in the cards when you have a situation where the ethical concern about getting the drug to people on placebo dominates the conversation.”

An independent data safety and monitoring board, which had looked at the preliminary results of the NIAID trial, determined it had met its primary goal of reducing hospital stays.

On Tuesday evening, that information was conveyed in a conference call to scientists studying the drug globally.

“There are literally dozens and dozens of investigators around the world,” Fauci said. “People were starting to leak it.” But he did not give details of where the unreported data was being shared.

I smell bullshit here. What probably really happened is that he was under enormous pressure to release the results. It was also…unwise…to discuss the results with so many scientists until the manuscript reporting the results of the trial had at least been submitted for publication. I agree with the scientists who had “expected it [the trial data] to be presented simultaneously in a detailed news release, a briefing at a medical meeting or in a scientific journal, allowing researchers to review the data.” I also agree with Dr. Eric Topol, referring to the Chinese RCT and this one:

“That’s the only thing I’ll hang my hat on, and that was negative,” said Dr. Eric Topol, director and founder of the Scripps Research Translational Institute in La Jolla, California.

He was unimpressed by remdesivir’s modest benefit.

“It was expected to be a whopping effect,” Topol added. “It clearly does not have that.”

Indeed, given that the pre-test probability of remdesivir having a significant effect was low, meaning that this trial is probably just noise:

https://twitter.com/markhoofnagle/status/1256242045821337600

Indeed, I’m not only unimpressed with the modest benefit reported, I question whether there really was any benefit at all, particularly in light of the Chinese trial, which found zero difference in viral load in the remdesivir group.

The whole thing looks damned fishy, and we can’t judge the study until it’s actually published. Meanwhile, whatever the true reasons for releasing the study results this way, mission accomplished. The negative effect of the Chinese study on Gilead’s stock price was successfully countered and remdesivir becomes a de facto standard of care for patients hospitalized with COVID-19. Worse, no further trials of remdesivir versus placebo will be possible, because it’s been declared that remdesivir “works” against COVID-19 and is the new standard of care! As Mark Hoofnagle put it in a great Twitter thread, that echoes my thoughts:

https://twitter.com/markhoofnagle/status/1256242068588019718
https://twitter.com/markhoofnagle/status/1256242071209476098

It’s worse than that. If remdesivir is now the “standard of care” for hospitalized COVID-19 patients, it now becomes unethical to randomize them to a placebo group testing ANY new drug for COVID-19. Trials will now have to compare remdesivir alone to remdesivir plus experimental drug. We’ll probably never know now for sure if remdesivir is truly effective against COVID-19.

But Gilead will make billions and billions of dollars.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

122 replies on “Remdesivir: Gilead wins with unimpressive results announced by press release”

But Gilead will make billions and billions of dollars.

Ohh! What a giveaway — That is exactly something a pharma shill would say.

I guess people should have jumped up and put the Robinhood app on their fondle slabs and ‘bought the dip’, after all.

Shares of Gilead (NASDAQ:GILD) plunged on a Financial Times report which implied that the company’s potential novel coronavirus treatment, remdesivir, flopped in its first randomized clinical trial. As of this writing, GILD stock was down more than 6% on the news.

But investors shouldn’t read too much into this Financial Times report, which cites accidentally published documents from the World Health Organization. After all, the Chinese study which the documents refer to had shortcomings. It was under-enrolled. It was incomplete. And it did not produce meaningful or conclusive results.

Now, I wouldn’t go all in. There’s a lot of uncertainty surrounding remdesivir and the stock at the moment. But I do expect robust clinical trial data to be released in May. That data should be positive, and corroborate positive early findings about remdesivir.

If so, then today’s dip sets up Gilead stock for a big May.

https://investorplace.com/2020/04/buy-the-dip-in-gild-stock-because-remdesivir-may-not-be-a-flop/

Note that they say “inconclusive results” about the Chinese RCT and not “negative” (i.e. no reduction in viral load).

Things that make the SEC you go hmm.

Remember when Gilead, after it purchased Sofosbuvir from Pharmasett, refused to cooperate with the pharmaceutical company that owned Daclatasvir (Bristol Myers Squibb), the companion drug of the cure for some genotypes of hepatitis C? I suspected Gilead wanted to corner the market with its own companion drug, Ledipasvir, that took more time to develop while patients continued to suffer, sometimes dying, from hepatitis C. Remember the Initial $90,000 price tag for Harvoni? My suspicion could be incorrect, but I’ll always wonder.

For a long time, I wondered why The Lancet published Wakefield 1998 case series – why such high impact journal published a case series with only 12 children? My own answered to me was that no way The Lancet or other such impact journal would published case series like this anymore. Even less impact and relevant journals publicly state they don’t accept case series. Apparentely I was very wrong, as NEJM has published a case series with remdesivir for covid.

Actually one of my publications during my PhD did involve a case series: patients with primary antiphospholipid syndrome (APS) that had thrombosis again while being given rivaroxaban (direct oral anticoagulants – DOAC). We know we didn’t prove anything, but we hypothetize that triple positive APS patients were at higher risk of thrombosis when using DOACs.
Interestingly, the first place I submitted the paper didn’t accept it, so I had to submitted to a less relevant journal. Both journals definitely are way less relevant than The Lancet and NEJM, obviously.

Just to be clear. I think there is space to publish case series about diseases manifestations. But case series about treatment benefits looks like just that: an attempt to show something works without the proper method that would show it doesn’t.

I was reading on CNN this morning that Trump is offering almost half a billion dollars to a company to produce a vaccine for the SARS CoV2 virus. The company has never brought a vaccine to market before, and it appears he selected them because they claim they can do it fast! I am so worried that some company will bring a bad vaccine to market (fast!) that not only will do harm to Covid 19 vaccinated people, but will add fuel to the anti-vaccine movement overall, causing an increase in measles and other diseases we should be done with. Either that, or they will be unable to produce it at all, and we’ve thrown away another half a billion

Indeed – the Orange Moron saying he is ‘in charge’ of Operation Warp Speed is hugely worrying. The man wants a vaccine pre Novemeber 3 – he wants to say he made it happen. How many safety protocols will be ignored? How many worrying side effects will be surpressed? How many researchers will be bullied into silencing their concerns? Could be a cure way worse than the disease. I stronlgy suspect OWS will come out with something within a few months – purey for politcal reasons. I won’t be lining up to take it… .. .

It’s worse than that. If remdesivir is now the “standard of care” for hospitalized COVID-19 patients, it now becomes unethical to randomize them to a placebo group testing ANY new drug for COVID-19. Trials will now have to compare remdesivir alone to remdesivir plus experimental drug.

What does that do for all other trials? Does it just now require them to carry on but add a drip? Is that only in the US?
What about the ongoing tests for other stuff like the nicotine in France and the estrogen on the east and west coast here (both, probably not so rigourous clinical but because observational studies of who come into the hospital lead to they may have a positive effect no matter how little understood the mechanism.)?

I’m no doctor as the only medical training I had was puckering up to a doll after pumping it 5 times (now recommended 30 because CO2 stimulates one to breath) and having worked half way through Time-Life Home Surgery #3 of a 36 volume set. But my scatter-knowledged, self medicating, short bus commuter self would be getting on

— estradiol patch
— nicotine patch
— nitric oxide or NO+boner pills (treat me like a ‘blue baby’); provided one is not already intubated.

All of those things would seem to be innocuous; Is remdesivir safe as baking soda or counter indicated to any of the above or would a hospital just refuse my self-recommended course and, being the good little bureaucrat loyalists they are, tell me I can’t have a magnesium supplement and to stop pulling the remdesivir tube out and just deal with my rectal prolapse that gives me forevermore?

yes dosed up with vicks..vaporub ointment…and….the vicks inhaler…..& fresh air…for your lungs….yes …happy bob from oz cheers….8

@ robert walton

What’s a “vaporub ointment”? Please educate me…

vicks is a world wide product,,goggel up active ingredents,…i wipe my nose in lets with a cotton bud on bed time,,,with product or as i think i need another hit ?? & also there in halers i have used for over 35 years …i gave up smoking back then using this item,,hence …..just saying ..yes ..happy bob from oz cheers …8

Vicks Vaporub is a stenchiferous mixture of petroleum jelly, camphor, menthol, eucalyptus oil, turpentine oil, and other miscellaneous stinkum. It’s been around for over a century. Users believe it relieves nasal congestion. It is reputed to be useful, when applied right under your nose, for masking the smell of rotting corpses. I would agree that it smells somewhat better than the average rotting carcass.

That shit killed a thousand times more children from accidentally aspirating it back in the day than the latest scandal of Hunnycut vitamin E acetate vaping scandal that was killin’ off of thc vapers getting ripped off by it being diluted by the stuff.

It turns out that it is not so good to inhale oils or fats into one’s lungs.

ok tim…what protocol have u got for us ??? yes oils or fats passing into your/our lungs …oh really tim happy bob from oz cheers 8

Seriously? You’re only supposed to put Vaporub on the chest. Body heat turns it into a vapour that gets inhaled. Were people putting it in their mouths or nostrils?

@ Julian

“Were people putting it in their mouths or nostrils?”

They could do worse…

Were people putting it in their mouths or nostrils?

Yes, Julian Frost. Bob mentions smearing a little with a cotton ball — which should be perfectly safe — but my grandmother would dip her finger in and stick globs of it all around just inside the nostrils.

https://en.wikipedia.org/wiki/Lipid_pneumonia

(Should be ‘lipoid’?) I guess a sleeping, stuffy kid would maybe give a big sniffle and sometimes the jelly would get in their lungs.

It is unconscionable to me all the hype and fear generated and being used to push for vaping bans over something that was, in retrospect, obvious from day one (I think the bastards knew and just let it continue to make the case against thc/cbd vaping and the mommies of the world just extended that to all vaping).

After a rash of suspected vape pen-related lung disease cases nationwide, the chemical makers responsible for selling new cannabis additives appear to be reacting, and evidence of their sales practices are emerging.

https://www.leafly.com/news/health/some-vape-cart-additive-makers-pull-products-others-go-dark

“Were people putting it in their mouths or nostrils?”

They could do worse…

Yah, back when I was an undergrad, we managed to convince my roommate that Noxzema was just the ticket for pruritus ani.

Annnd, was his itchy because you dripped urushiol on his toilet paper roll?

Power move, satan; You go boy.

@ Julian Frost May 2, 2020 at 5:54 am
I remember getting a bit of Vicks rubbed on my nose as a child. And just a few months ago my doctor recommended it for a bit of scar tissue–no open wound.

The best I have heard was a friend telling me she fed her 20-year-old cat about 20ml of Vick every day.

Maybe she gave the cat Vick’s because it has petrolatum – so for hairballs? Hairball formulae use it,
However, I wonder about the other ingredients like menthol, camphor and turpentine oil which could be toxic.

Cats sometimes have bizarre food preferences and have been know to savor antifreeze- dangerously -when it drips from cars,
The important question; did the cat live?

He expressed concern that leaks of partial information would lead to confusion. Since the White House was not planning a daily virus briefing, Fauci said he was invited to release the news at a news conference with Louisiana Gov. John Bel Edwards(D).

“To forestall the possibility of leaks of partial information, I’m going to leak partial information”.

Now listen here, you little shit…

p.s. where is the Limbaugh crowd when one is in need of blog hits? (sorry, Orac. You are gonna starve on this one) Yea, they have been advised not to pollute their computers by visiting this site (It has nasty trojans, and viruses, and thought.)

In long twitter exchange mainly led by James Heathers, has anyone noticed that there are a series of tweets by Didier Raoult ?

One tweet reads:

Could Anthony Fauci explain why the investigators of the NIAID remdesivir trial did change the primary outcome during the course of the project (16th April)?
Removing “death” from primary outcome is a surprising decision.

As Orac makes clear, the research is weak at best and even what does exist finds a shortening of duration; but not reduction in deaths or long term sequelae. However, even if one were to accept this, what about side-effects. In a quick search of the web I found the following two:

WHAT ARE SIDE EFFECTS OF REMDESIVIR (RDV)?

In the Ebola trial, researchers noted side effects of remdesivir (RDV) that included:
Increased liver enzyme levels that may indicate possible liver damage
Researchers documented similar increases in liver enzymes in three U.S. COVID-19 patients
Typical antiviral drug side effects include:
Nausea
Vomiting

Found at: https://www.rxlist.com/consumer_remdesivir_rdv/drugs-condition.htm

Side effects
The most common adverse effects in studies of remdesivir for COVID-19 include respiratory failure and blood biomarkers of organ impairment, including low albumin, low potassium, low count of red blood cells, low count of platelets that help with clotting, and yellow discoloration of the skin. Other reported side effects include gastrointestinal distress, elevated transaminase levels in the blood (liver enzymes), and infusion site reactions.
Other possible side effects of remdesivir include:
Infusion‐related reactions. Infusion‐related reactions have been seen during a remdesivir infusion or around the time remdesivir was given.[8] Signs and symptoms of infusion‐related reactions may include: low blood pressure, nausea, vomiting, sweating, and shivering.
Increases in levels of liver enzymes, seen in abnormal liver blood tests. Increases in levels of liver enzymes have been seen in people who have received remdesivir, which may be a sign of inflammation or damage to cells in the liver.
Found at: https://en.wikipedia.org/wiki/Remdesivir

So, if it does shorten duration, is it worth potential liver damage, respiratory failure and organ impairment? In other words is the cure potentially as bad as the disease.

And, as Orac and many commenters have made more than clear, one more example of Trump’s government, ignoring science, and jumping to conclusions.

And once more I suggest reading the following:

Jeanne Lenzer and Shannon Brownlee (April 28, 2020). Pandemic Science Out of Control. Issues in Science and Technology. Available at: https://issues.org/pandemic-science-out-of-control/

ADDENDUM

I found the following: “Particular laboratory features have also been associated with worse outcomes (table 2). These include: Elevated liver enzymes”

Found at: https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-epidemiology-virology-clinical-features-diagnosis-and-prevention?search=coronavirus-disease-2019-covid-19-…demiology-virology-clinical-features-diagnosis-and-prevention&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

So, one of the side-effects has been associated with worse outcomes. Not exactly a ringing endorsement of Remdesivir.

. . . The idea is that, if a signal of efficacy is found with one drug, that drug becomes “standard of care” and the trial is adapted to study how adding other experimental drugs compares to the “standard of care.” So what Dr. Fauci meant was that, based on the finding, going forward remdesivir will become the “standard of care” arm for the trial and the experimental arm will become remdesivir plus another experimental therapeutic. However, given that the FDA is on the verge of issuing an emergency use authorization for remdesivir to treat COVID-19, it looks as though remdesivir will become standard-of-care in general soon.

Thanks for making this point. I don’t believe I have noticed these, to me, subtly different uses or application of the “standard of care” phrase.

As for politics, spin, and jockeying for position by and within the Trump administration, it is now writ large and even decent people cannot seem to remain untouched by it.

For yet another drug that was supposed to be a game changer, I am unimpressed by its results. The whole mechanism is wrong. A drug with this mechanism would need to be almost a prophylactic for it to be hugely effective.

TWiV 608 has a good explanation of why these antiviral trials are unlikely to show strong results.
https://www.microbe.tv/twiv/

The peak viral activity occurs at about the time when noticeable symptoms appear. By the late period in the illness when Remdesivir is being tested, most of the virus has been cleared already.

But, we can’t start bringing everyone who has symptoms and tests postive in for daily IV treatments. EIDD-2801 being tested at Emory might be usable for that if it is effective since it is a pill.

You can listen to a real epidemiologist, Jeff Shaman from Columbia, explain the uncertainties in what our data are telling us about how this pandemic is spreading.

You can also hear him discussing what we are learning from mathematical models of this disease with Sarah Cobey from the University of Chicago on Science Friday from May 1.

https://www.sciencefriday.com/segments/covid-math-models/

The peak viral activity occurs at about the time when noticeable symptoms appear. By the late period in the illness when Remdesivir is being tested, most of the virus has been cleared already.

Yes indeed. Even more, to be successful, it needs to be given early before virus load gets high.

How is remdesivir compared with favipiravir? Looks like we are doing a trial of favipiravir vs the whole hydroxycloroquine business vs current standard of care. A very quick scan of the news story seems to show that favipiravir is similar to remdesivir, in purpose anyway.

It has been stated, “The mortality benefit of remdesivir has not yet reached statistical significance.”

It can also be written. “Yet, the mortality benefit of remdesivir has not reach statistical significance.”

MJD says,

The word “yet’ must never be used in science-speak, it’s to misleading. With respectful insolence, Orac did use the word “yet” once in this post.

You are bordering on “not even wrong” territory, Michael.

In the sense of having crossed through it into uncharted waters, perhaps.

Oh, and the measurement problem has yet to be resolved.

Well, there is ‘many worlds’ and ‘pilot wave’, gasp.

Bohmmm!!!

One thing they discovered is that the proteins involved have zinc atoms incorporated into their structure. This won’t surprise any biochemists, as zinc-containing proteins are common. But there’s been a steady flow of fringe treatments for the disease—including some involving chloroquine derivatives—in which zinc was a key component. We’ll have to see whether that changes now that it’s clear that zinc is needed to make copies of the virus (assuming that fact registers at all with the people prone to promoting fringe therapies).

https://arstechnica.com/science/2020/05/scientists-get-an-atomic-level-look-at-how-a-drug-blocks-the-coronavirus/

What is that saying about zinc? I’ve always heard that zinc was a good thing to have a high intracellular level of it to protect against viruses besides also being needed to make NO.

https://arstechnica.com/science/2020/05/nih-cuts-coronavirus-funding-amid-trump-comments-and-conspiracy-theories/

now that it’s clear that zinc is needed to make copies of the virus

Oh my. The plot, it thickens.
These one-month-old comments by proponents of CQ/HCQ are getting past their ‘best use date’ very quickly.

In other Covid-19 news….

Someone we all know ( @ gorskon) highlights recent protests by gun-totin’ loons in his area. Truly horrendous, as were other activities in Orange County, CA, such as attempting to storm the closed beaches. With flags yet.

In contrast, here in Liberatopia, a general order to close parks has been partially rescinded so I went to a nearby open space/ sports area: while the fields, courts and boat launch were all closed, pathways were not. Parking was restricted to control volume of visitors ( some areas shut entirely and others allowing alternate rows of cars) People wore masks! They maintained social distancing! Little kids rode tiny bikes with masks! Runners wore masks! True, some of the residents are Korean or Japanese born but not everyone .
It is extremely diverse. I did see something that made me laugh: two young Black women sat on the grass with a tiny baby and two wacky, small dogs when an elderly white couple approached them with their two small, wacky dogs: all dogs were on rather long leashes ( over 6 feet long I’d estimate). The humans hesitated for a while, probably thinking : Do dogs have to socially distance? They did eventually allow the dogs to interact but kept their distance from each other.
I’m glad that I live in Liberatopia.

“To the people who resort to threats and intimidation when asked to take a simple step to protect your community: shame on you. Our freedom as Americans comes with responsibilities, too,” the mayor tweeted. “We must find common ground and work together to deal with the circumstances our society is facing. Whether or not we agree on the details, we have to find ways to cooperate in the task before us.”

https://www.nbcnews.com/news/us-news/oklahoma-city-ends-face-mask-rule-shoppers-after-store-employees-n1198736

That really pisses me off. My respirator is a little, shall we say, unconventional (it is the 3rd iteration of an oreck vacuum cleaner bag on a short piece of dishwasher drain hose sticking out of a sealed mask from a cut off grape juice bottle and window seal stretch tape ankle wrap makes all the parts interchangeable between them and buying thirty bags made them only $2.50 a pop. (The OG model on the round v8 top restricted vision too much when looking down to use the chip reader machine)).

I’ll continue to wear that because nobody else around here can be arsed to even put on a wash cloth. What times we live in that some guy in a maga hat is going to stew me for perceived disrespect for Trump and looking silly at the same time. This is what black guys (and myself, a white guy) feel at traffic stops.

Someone we all know ( @ gorskon) highlights recent protests by gun-totin’ loons in his area.

I’m sure cancellation of the Boil Festival in Lansing has left many with irritation.

Heh heh.

considering other loons:
see @ thereal_truther who tweeted an NYT story/ photo ( 20 hrs)
anti-vaxxers join anti-shutdown activists and lookie lookie!
It’s our old friends, the three women from CA who famously wore red, white ( remember that tiered, short dress?**) and blue holding flags upside down ( a distress signal) in CA, NY ( for RFK jr) and NJ protests.
Well, here they are again.

They made to the NYT. Fame, fame, fame. Is it any wonder?

** how could I forget? I don’t only recall good fashion choices

Orac wrote: “What prompted me to write about remdesivir were headlines like “Dr. Anthony Fauci says Gilead’s remdesivir will set a new ‘standard of care’ for coronavirus treatment” that started popping up on Wednesday afternoon …”
Fauci just dropped down a level or two in my estimation of his commitment to rationality.

@ Reality

So: “Fauci just dropped down a level or two in my estimation of his commitment to rationality.”

Let’s look at the “Reality”: “America needs a federal government that assertively promotes and helps to coordinate that, not one in which experts like Tony Fauci and Deborah Birx tiptoe around a president’s tender ego.” I wouldn’t want to be in Fauchi’s shoes. If he openly criticizes Trump, he is out and staying in allows him to have some effect. Damned if he does and damned if he doesn’t. So, he has to balance his “committment to rationality” to trying to modify/reduce the insanity of Trump. If he resigned or was fired, could he have more of an influence? Maybe, maybe not. I would not want to be in his shoes! ! ! Personally, I would probably resign and try to get our media to listen to me. Just standing next to Trump would turn my stomach.

So, maybe you should live up to your “name” and evaluate “reality” not an idealistic world.

So you wouldn’t say what Fauci said and would quit, eh, Joel?
I wouldn’t say what Fauci said about “standard of care” which is basically his endorsement of this.
I believe Orac wouldn’t make that statement endorsing Remdesivir as the “standard of care”.
I don’t know of any self-respecting scientist who would make such a statement no matter what the pressure.
If I was pressured by DJT I would object but maybe agree to not make any statement pro or con about the subject – so as to keep my position and influence… but if someone asked me to say something I thought was not true I would not do it and refuse.
.
Fauci didn’t seem to have any problem cautioning against unwarranted optimism for CQ/HCQ even while DJT was championing the stuff. What is different about this?
.
That is the Reality of this Fauci statement.

@ Reality

You write: “Fauci didn’t seem to have any problem cautioning against unwarranted optimism for CQ/HCQ even while DJT was championing the stuff. What is different about this?”

Yep; but the only studies promoting CQ/HCQ was a fraudulent one in France and an in vitro study.

What about Remdesivir? First it is a nucleic acid analogue designed to directly disrupt replication of the viral genome. Chloroquine/Hydroxychloroquine were not even remotely designed to target viruses, though they have a moderate dampening effect on immune reactions, so they work for autoimmune diseases (e.g., lupus, rheumatoid arthritis); but, as I wrote in a previous exchange, the immune response in an autoimmune disease compared to a cytokine storm is like comparing 20 mile per hour winds to a category 5 hurricane, 160 mph winds. In addition, chloroquine/hydroxychloroquine have a large number of mild side-effects and some really serious major ones.

So, what did Fauci say about chloroquine? ““We’ve got to be careful that we don’t make that majestic leap to assume that this is a knockout drug. We still need to do the kinds of studies that definitely prove whether any intervention is truly safe and effective,” Fauci, who is also a member of the White House coronavirus task force, said during an interview on “Fox & Friends. . . “We don’t operate on how you feel, we operate on what evidence and data is,” Fauci said, adding that it was “not a very robust study” or “overwhelmingly strong.”” (Concha, 2020 Apr 3)

Now, what did he say about Remdesivir: “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.” Fauci said the median time of recovery for patients taking the drug was 11 days, compared with 15 days in the placebo group. He said the mortality benefit of remdesivir “has not yet reached statistical significance.” The results suggested a survival benefit, with a mortality rate of 8% for the group receiving remdesivir versus 11.6% for the placebo group, according to a statement from the National Institutes of Health released later Wednesday. “This will be the standard of care,” Fauci, director of the National Institute of Allergy and Infectious Diseases, added. “When you know a drug works, you have to let people in the placebo group know so they can take it.” “What it has proven is a drug can block this virus,” he said. (Lovelace, 2020 Apr 29)

“The data shows that remdesivir has a clear-cut, significant, positive effect in diminishing the time to recovery,” Fauci said at the White House on Wednesday. The data he referred to is from a large study of more than 1,000 patients from multiple sites around the world. Patients either received the drug, called remdesivir, or a placebo.

Dr. Michael Saag, associate dean for global health at the University of Alabama at Birmingham, said the results seemed promising. Antiviral drugs such as remdesivir tend to work earlier in the course of an illness, so “the thing that I think is important in this study is the patients had advanced disease,” said Saag, who is not involved with any remdesivir trials. (NBC News (2020 Apr 29)

Hospitalized patients with advanced COVID-19 and lung involvement who received remdesivir recovered faster than similar patients who received placebo, according to a preliminary data analysis from a randomized, controlled trial involving 1063 patients, which began on February 21. The trial (known as the Adaptive COVID-19 Treatment Trial, or ACTT), sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is the first clinical trial launched in the United States to evaluate an experimental treatment for COVID-19. 

An independent data and safety monitoring board (DSMB) overseeing the trial met on April 27 to review data and shared their interim analysis with the study team. Based upon their review of the data, they noted that remdesivir was better than placebo from the perspective of the primary endpoint, time to recovery, a metric often used in influenza trials [my emphasis]. Recovery in this study was defined as being well enough for hospital discharge or returning to normal activity level. . . Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group (p=0.059).
the group receiving remdesivir versus 11.6% for the placebo group (National Institute of Allergy and Infectious Diseases (2020 Apr 29).

So, first I’d bet you don’t understand how nucleic acid analogues work?
Second, though I tend not to rely on one study, this one was fairly large and the shortening of time to recovery was clinically significant, “defined as being well enough for hospital discharge or returning to normal activity level.” And Dr. Michael Saag: “Antiviral drugs such as remdesivir tend to work earlier in the course of an illness, so “the thing that I think is important in this study is the patients had advanced disease,”

Standard of Care is more a legal definition than a clinical one. Basically it reduces risk of malpractice lawsuits.

While I probably would not have called it “standard of care”, instead clearly stating that based on the recent trial, it is currently the best we have to offer or something to that effect.

So, Fauci didn’t call it a cure, didn’t claim it reduced mortality, though indications it did, and based on over 1,000 patients, found it reduced hospitalization and return to normal life by a clinically significant margin, the standard used for flu studies. Again, I would have been more cautious in my working; but your rank attack on a man who knows more about infectious diseases that you, I, and many others, a man who has dedicated his life to preventing and dealing with them is just plain sickening. Your black and white view of Fauci is how antivaccinationists and other adherers to unscience see the world. And an MPH probably means a couple of lower level epidemiology courses. So, the old saying: A little knowledge is a dangerous thing, coupled with a personality that prefers a dichotomous world is very very problematic.

Only time and further studies will tell if Remdesivir really does shorten recovery time and, perhaps, also lowers mortality. Right now, we have nothing else and I wouldn’t jump on something because of this; but the over 1,000 patient study isn’t nothing.

Just to be clear, Orac’s critique is valid; but, as he says, by this time one becomes perhaps overly skeptical given Trump’s insanity. How cautious should Fauci have been? People are becoming desperate. The risks from Remdesivir are extremely low, so currently, either use it or continue as is. If there were significant risks and the one study had been one a much smaller group, the scales would be different. And, though Orac is right they changed the outcome points, as mentioned, shortening of recovery time is a criterion used for treatment of flu, so, though not, perhaps, the best end-point, it is certainly not the same as some studies using endpoints such as lowered cholesterol without looking at deaths. They did look at deaths and though not significant, in the right direction. By the way, do you even understand significance levels? Though only one study, p=0.059 isn’t far from p=0.05.

References:

Concha, Joe (2020 Apr 3). Fauci warns there’s no ‘strong’ evidence anti-malaria drug works on coronavirus

Lovelace, Berkeley (2020 Apr 29). Remdesivir coronavirus drug trial: Dr. Fauci says it will set new standard of care. CNBC  

National Institute of Allergy and Infectious Diseases (2020 Apr 29). NIH Clinical Trial Shows Remdesivir Accelerates Recovery from Advanced COVID-19

NBC News (2020 Apr 29). Remdesivir shows promising results for coronavirus, Fauci says 
 

People are becoming desperate. The risks from Remdesivir are extremely low [citation needed], so currently, either use it or continue as is.

Yup, an IV treatment is just the ticket.

By the way, do you even understand significance levels? Though only one study, p=0.059 isn’t far from p=0.05.

SPLORF. Do you understand significance levels? Can you actually define what they are supposed to mean? P = 0.05, as is widely known (psychologist Ulrich Schimmack’s gymnastics notwithstanding) to be, shall we (tinw) say, Not Scottish.

It’s time to take down your shrine to Fisher.

By the way, do you even understand significance levels? Though only one study, p=0.059 isn’t far from p=0.05.

Oh dear.

Let me put it this way, a p <0.05 is OK for ordinary wear in the garden. If you are contemplating going on a hot first date, you would want something much smarter than this.

A p value of 0.059 is nothing to get excited about. It falls into the nearly pregnant category.

@ Chris Preston

First, the point I was making is that one of the currently used decision points, 0.05 with one or two more cases would have been reached. Second, a well-done study on a large sample size and 0.05 has been used for making decisions.

Historically, a number of studies that didn’t quite reach 0.05 when combined in a meta-analysis did. And one major problem is that journals often use 0.05 as cut-off criteria for publications, thus, not allowing for possible further replication studies or use in meta-analyses, which often manage to find unpublished studies.

So, once more we have someone who sees the world in black and white. Oh well. As numerous studies have found, more than 80% of Americans don’t really understand the basics of research. Check out the books I recommend in one of my comments. You might learn something.

Too skeptical an attitude leads to paralysis, too little skepticism can lead to harms. Somewhere in the middle, Aristotle’s Golden Mean, Swedish “lagom är bäst”, etc.

She said she wasn’t surprised that a coronavirus wrought this devastation, that China minimized what was going on or that the response in many places was sloppy and sluggish. She’s Cassandra, after all.

But there is one part of the story she couldn’t have predicted: that the paragon of sloppiness and sluggishness would be the United States.

“I never imagined that,” she said. “Ever.”

…Having long followed Garrett’s work, I can attest that it’s not driven by partisanship. She praised George W. Bush for fighting H.I.V. in Africa.

But she called Trump “the most incompetent, foolhardy buffoon imaginable.”

…Referring to the Centers for Disease Control and Prevention in Atlanta and its analogues abroad, she told me: “I’ve heard from every C.D.C. in the world — the European C.D.C., the African C.D.C., China C.D.C. — and they say, ‘Normally our first call is to Atlanta, but we ain’t hearing back.’ There’s nothing going on down there. They’ve gutted that place. They’ve gagged that place. I can’t get calls returned anymore. Nobody down there is feeling like it’s safe to talk. Have you even seen anything important and vital coming out of the C.D.C.?”

…America needs a federal government that assertively promotes and helps to coordinate that, not one in which experts like Tony Fauci and Deborah Birx tiptoe around a president’s tender ego.

https://www.nytimes.com./2020/05/02/opinion/sunday/coronavirus-prediction-laurie-garrett.html

Careful, you’re getting close to receiving a misspelled rant with full caps and a strange punctuation style.

@ Narad

Yep, I understand what a p-value is. It is an artificial cut-off point to make a decision. The decision is simply was the result from the Independent variable(s) or some other uncontrolled variable(s) that by random chance ended up more in one group than the other. With a medical intervention, the decision is whether to apply it or not. And, no decision should be permanent, always possibility no matter how well one or a few studies are carried out, some later studies may find only subgroup valid or not. However, in epidemiology where the goal is to try to understand something, not make a decision, confidence intervals are used. So “It’s time to take down your shrine to Fisher” Not a shrine, simply acceptance that it isn’t an absolute; but a strategy for making decisions.

So get off your fucking high horse. Once more all you do is irritate rather than add to the discussion.

ADDENDUM

And do you even understand that when Fauci called it standard of care, he was simply saying that if doctors use it they are fairly protected against lawsuits, not that it has been shown by numerous studies to be strongly scientifically validated. In fact, we have a number of medical procedures used today that were not based on even one large placebo controlled randomized trials; but grandfathered in. Since most people don’t understand this, perhaps, it was a bad choice of terminology; but I certainly wouldn’t lower my respect for Fauci based on this; but, someone who arrogantly calls himself “Reality” and sometimes even you just want to see the world in black and white. Fauci’s, perhaps, poor choice of terminology and that erases a lifetime of achievements? And, just possibly he also reacted to several months of suffering of the American people and was glad something had “some” valid science behind it, not just a study of 1,000; but knowledge of how nucleic acid analogues work. On the whole, despite some negative studies, Remdesivir, a nucleic acid analogue, may work and the risk of severe side-effects in extremely low, so far raised liver enzymes, not found in the one large study.

And do you even understand that when Fauci called it standard of care, he was simply saying that if doctors use it they are fairly protected against lawsuits, not that it has been shown by numerous studies to be strongly scientifically validated.

Why are you addressing this to me? I haven’t said a damn thing about Fauci.

Is that the same “standard of care” when your local GP gives you or a loved one an influenzas vaccine and the next day you or that loved one is inexplicably disabled? It seems to be me that “Standard of Care” is part of an “out” for law suits not being made on the Vaccine company. I bet the Tobacco Companies in the 50s and 60s wish they had tagged that one somehow!

So get off your fucking high horse. Once more all you do is irritate rather than add to the discussion.

The irony, it burns.

@ Narad

You write: “Why are you addressing this to me? I haven’t said a damn thing about Fauci.”

True; but you jumped on the bandwagon when I addressed p-values and you make so many bull shit comments that I sometimes confuse you with other a-holes. As I’ve written several times, sometimes you actually contribute to the conversation, even link to worthwhile papers; but often you just interject worthless phrases.

As I wrote in another comment, I have NO problem admitting when I’m wrong which happens; but I don’t just make comments to irritate people. I comment when I disagree and try to martial a reasonable argument.

@Joel A strategy to make decisions? Well what framework do you use may I ask? Is it logical – hope so! Does it use all the information? Hope so! Your p-number is simply that – a piece of information. It has it own provenance which may lead you to be more or less certain about it itself. You have other information. How likely was the result -what was the prior.
Let me, in an entriely unprovable way – blow my own horn.When hydroxychloroquine started being touted as a otetial remedy I remarked to my parnter things like ‘if it works we may have dodged a bullet here!’ and ‘ maybe humanity has fluked its way ouot of it’. I have no real knowledge of the relevant fields, just the observation that the reasons for trying it seemed failry thin and the general knowledge that one does not normally cure a disease by just reaching up to the medicine cabinet. Do you think I was right to state that if hc was a cure that would have been a fluke? Did you have any prior thoughts on that?
For the corona virus specifically, there are so many influences – ranging from the altruistic, compassionate desire of researchers to find a cure, and quickly, to the venal corruption of some of the actors, and where doctors are saying things like ‘ so man are dying we don’t have time for controlled studies’ I would make sure you look at p numbers as information, not some form of definite reality.
When it comes to making those decisions I hope you do use a logical system that incorporates all the information – it would actually be irrational not to! There is such a system, but its name escapes me at the minute…

@ Jools

Do you know what a meta-analysis is? Combining a number of studies and, yep, they use p-values and confidence intervals. Biological plausibility is often added to the mix (but one can make a biological argument for almost anything). Benefit/cost analysis play a role (but depends how one weights them and which variables one chooses). What you, Reality, and Narad miss is that I was simply pointing out that a few decimals different and Fauci and others would have called the mortality reduction significant. I don’t even like the phrase “statistical significance” because it has nothing to do with importance, simply as I explained above, with whether one decides that an outcome was more or less likely to have been caused by unmeasured variables that ended up more in one group than the other. And whether 0.05, 0.001 etc. the result could have been due to something other than the independent variable. As more and more studies are done, the probability goes down; but never zero.

The best book I have ever read: Merwyn Susser (1973). Causal Thinking in the Health Sciences: Concepts and Strategies in Epidemiology. Used copies available on Amazon.com and in many university libraries

A short chapter is also good: Kenneth Rothman and Sander Greenland (1998). Modern Epidemiology (2nd Edition). Chapter 2: Causation and Causal Inference.

Also: Daniel Kahneman et al. (1982) Judgment under uncertainty: Heuristics and biases.

I’ve got many more; but bottom line is that “causation” is NEVER “proven” we just make a decision based on various criteria and heuristics.

@Joel The thing about Dr Faucci illustrates somewhat a point. A result can be said to be ‘statistically significant’ at a given level.
That is purely a definition. It might have better if it has been called ‘statistically moonish’ or something – it would have made zero difference to anything if it had.
But now we move from that definition to common language – ‘significant’ and binary classification, which then seems to be moved almost to ‘proven fact’ and it is this that is fed into decision making – even if one holds the inconsistent mental state that ‘it may change’.
Now P-numbers, confidence intervals, all that, can be given appropriate theoretical background, and indeed in many or most normal circumstances one pulls the handle, out pops the result and it does indeed have the weight you give it. Theres nothing wrong with handle pulling on mathematical procedures, lots of people including myself do it all the time, but you have to know – you should want to know – that there is theoretical justification, and you have to be aware of its implicit assumptions and limitations. Maybe you can go your entire career without these considerations, or maybe you can be trying to analyse a whole bunch of small, badly controlled studies carried out in an atmosphere where basic trust – from top to bottom in the process – is attenuated.

But – you have really managed to lower my confidence in medical decision making!

“Biological plausibility is often added to the mix (but one can make a biological argument for almost anything).
Benefit/cost analysis play a role (but depends how one weights them and which variables one chooses). ”

Say what? This sounds like we’re in real ad hoccery land and lost without a guide!
So what if one can make biological argument for almost anything? Are you suggesting that when biological plausibility is included its sort of some authority sticking their finger up in the air? This is not setting a prior. What the prior should be can often be a difficult question – it is actually a matter of research in general, it is the current limit of the science. So what? Science doesn’t guarentee giving you all the answers, or that it will make your life easy.And anyway I can easily think anyway of how we might go about getting useful priors in a systematic way.
Furthermore, just because you choose not to include it in your analysis is irrelevant.
It just means you have implicitly assumed priors on all other information such that they are neutral to the data.
Probably the implicit assumption that any potential cure is as likely to work as not work, or perhaps slightly lesser condition is that all potential cures are all as equally likely to work.
Its a good exercise to push to the boundaries. Trying saying aloud ‘Given new disease X all potential cures are biologically equally plausible’, or, ‘Given a new disease X compound Y is (biogically speaking) as equal to work as not’. These are ridiculous statements surely. So biological plausibility should be included in your analysis, and you should exert your maximum effort to do it properly.

Fortunately, most of the time the actual evidence far outways the setting of priors so you get off with iffy decision making process.

Your point about benefit /cost analysis made me say ‘what’ twice. I’m not sure I understand fully how medical decisions can be made without it. Also,’depends how one weights them and what variables you choose’ – it would be beyond bizarre if you were including factors in your analysis where this wasn’t the case.
But really, I think we’re in pretty much the same territory as above. Even if you don’t explicitly have them (still not clear what your decision criteria is without them..)
if you make several decisions using your ‘system’, and by pure chance your system happens to be consistent,(if it’s not consistent where does that leave you?) then we can probably derive a Cost/Benefit that ‘explains’ your decision. More than you can do apparently, though I stand to be corrected when you tell me how you explain the decision ‘We should give the patient X’ without using cost/benefit terms!

Maybe you should start with the authors’ other books that claim that Chronic Fatigue Syndrome is an infectious disease and equate it to AIDS. Literally, apparently.

Sounds like very colorful reading.

Then again, you’re likely better off turning to a top fantasy or science fiction book for something like that; the accuracy will be as good or better, and the writing, plot development and characters guaranteed to be good. I recommend Lois McMaster Bujold or David Weber or David Brin for some very good examples.

Hi Dorit. Thank you for the recommendations. However, I find this kinda’ stuff way more interesting. https://wjla.com/news/local/cdc-shut-down-army-germ-lab-health-concerns

Oh, how is GSK doing in the run for the Convid-19, oops, I mean Covid-19 vaccine? How is your stock performing? https://www.gsk.com/en-gb/media/press-releases/clover-and-gsk-announce-research-collaboration-to-evaluate-coronavirus-covid-19-vaccine-candidate-with-pandemic-adjuvant-system/

Collaborating with China-based Clover Biopharmaceuticals…. Chinese biologics/biosimilars? Ew. Scary.

Chinese biologics/biosimilars?

Do you even know what biologics/biosimilars are?