I feel bad for this man and his wife, but there’s a strong dose of irony in this story from USA Today (click on title below to read):
An excerpt:
Keith Smith, whose wife had gone to court to have his COVID-19 infection treated with ivermectin, died Sunday evening, a week after he received his first dose of the controversial drug.
He was 52.
Smith was in a hospital in Pennsylvania for nearly three weeks and had been in the hospital’s intensive care unit in a medically induced coma on a ventilator since Nov. 21. He had been diagnosed with the virus on Nov. 10.
His wife of 24 years, Darla, had gone to court to compel the hospital, UPMC Memorial, to treat her husband with ivermectin, an anti-parasitic drug that has not been approved for treatment of COVID-19.
York County Court Judge Clyde Vedder’s Dec. 3 decision did not compel the hospital to treat Keith with the drug, but it did allow Darla to have an independent physician administer it. He received two doses before Keith’s condition grew worse, and the doctor halted the treatment. . .
. . .Darla sued UPMC to treat her husband with ivermectin after reading about similar cases throughout the country, all filed by an attorney in Buffalo, N.Y. She was assisted by a group called Front Line COVID-19 Critical Care Alliance, which promotes the use of ivermectin in the treatment of the virus.
He received his first dose on Dec. 5, two days after Vedder’s decision in the court case. After Keith received a second dose, the doctor overseeing the drug’s administration – a physician not affiliated with UPMC – ended the treatment as Keith’s condition deteriorated.
Here’s a photo of Keith and Darla; note the caption (click photo to enlarge):
Now there may have been nothing that would save this man once he was infected, and, after all, this is only one anecdote, not a disproof of the claim (made, among others, by Bret Weinstein and Heather Heying) that ivermectin is an efficacious preventive and cure for Covid-19. But I point out that we still have no good evidence that ivermectin can do either of these things, while we have strong evidence not only for the efficacy of vaccination (particularly with a booster), and now also for the new Prizer antiviral pill, which, if given within three days of the onset of symptoms, reduces the risk of hospitalization and death by 89%. Even if ivermectin proves to have a marginal effect (and, given the studies, that’s the most it could have), it’s no match for existing treatments.
To see a summary of the “evidence”, read this short piece in Stat, a site for health and health-and-business related news (click on screenshot):
As I’ve already pointed out, many past studies purporting to show an effect of ivermectin were fatally flawed in different ways, including cases of apparent data-faking as well as post facto analysis without proper controls. Here’s a summary of the article above:
Where to look for higher quality data? A group called the Cochrane Collaboration spends its time conducting meta-analyses of the best-conducted clinical trials. After excluding dozens of ivermectin studies with “high risk of bias,” the collaboration left little room for optimism: “Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent Covid-19.” The group recommended that ivermectin use be restricted to clinical trials that might actually generate high quality data.
The World Health Organization and the Infectious Diseases Society of America concur. Even Merck, an ivermectin manufacturer, avers that there is “no meaningful evidence for clinical activity or efficacy in patients with Covid-19.” And just last weekend the FDA warned people not to use the drug as a treatment for Covid-19.
An FDA tweet. (Note: yes, people, I know that ivermectin has valid uses in humans for eliminating lice and parasites, so don’t bother to correct me. We’re talking about viruses here.)
You are not a horse. You are not a cow. Seriously, y'all. Stop it. https://t.co/TWb75xYEY4
— U.S. FDA (@US_FDA) August 21, 2021
Note that Stat reports that a properly designed study is in progress (my emphasis below).
Yet ivermectin boosters and merchants have convinced many to use this therapy for Covid-19, particularly in Latin America where its use is so widespread that researchers have had difficulty recruiting patients for trials of other potentially effective products. In June, YouTube suspended the account of Sen. Ron Johnson (R-Wis.), a member of the Senate Homeland Security and Governmental Affairs Committee, for a week for spreading misinformation about ivermectin and hydroxychloroquine.
I’ve also criticized Weinstein and Heying, who work in my own field, for not only denigrating vaccines, but pushing ivermectin. Those who heeded their advice have been put in danger.
The increased demand for the drug, combined with enhanced scrutiny from pharmacists, has caused shortages of veterinary formulations of the drug. Inevitably, a spike in calls to Poison Control Centers connected to the use of veterinary ivermectin has followed.
And the money paragraph:
The University of Oxford’s rigorously designed PRINCIPLE trial is now trying to determine if ivermectin actually benefits people with Covid-19. But until those results come in, I urge people to heed the lessons of hydroxychloroquine, bleach, and all the other purported Covid-19 cures: effective treatments will be identified through systematic scientific study, not by wishful thinking, fabrication, or miracles.
Remember the Hippocratic Oath’s dictum: “First, do no harm.”
If the Oxford study shows ivermectin has appreciable value in preventing or curing Covid-19, I will admit that I was wrong, though I reserve the right to judge whether such an effect is sufficiently strong to make the drug more valuable than current treatments.
Likewise, if the Oxford study shows very low or no value of ivermectin in preventing or curing Covid-19, I expect that Weinstein and Heying will issue a statement saying, “We were wrong. We may have put people in danger.”
But I can already say with assurance that anybody following their advice, dosing themselves with ivermectin and avoiding vaccination, is doing precisely the wrong thing.
I hope people remember that death is not funny. I have seen far too many people expressing glee that other human beings have died. Lately, I have seen too many people from the Left and Right gleefully rejoicing when someone dies.
Completely agree.
Whoops, sorry. I didn’t mean to be so redundant. I paused, got distracted by a cat, and forgot to reread the first sentence as I edited the second. One of those mornings.
There is schadenfreude, which to me seems to be an autonomic response in my frontal cortex. Can’t help it. But yes, one should suppress glee over death except in unusual circumstances.
Cats, meanwhile, are always worth the distraction.
Anonymous, Sorry: “glee” may be a bit strong. But the fact remains that this is a war (call it “civil” if you must), and the progressives are losing it.
Due to the laws now being passed by GOP-controlled state legislatures, not only making voting more difficult, but essentially giving them the ability to, for any reason or no reason at all, simply erase the usual slate of electors and replace them with others of their own choosing, it appears that the days of Democrats being elected to national office are over, at least in the near term. Yes, Der Drumpf WILL BE reëlected in 2024. The Dems have ZERO plans to stop any of this.
If this happens, science will once again be devalued. The country will AGAIN be run by coal and petroleum interests. MANY more people will die. So…every Qcumber, every vaccine denialist, every Trumputo that dies now at least makes it possible that more live will be saved later. “Glee”? No, wrong word. But the math is pretty clear.
I’ll add a qualifier here. While I take no pleasure in the death of people, there is something worth grinning about when individuals who know better and wantonly issue public health statements to vunerable people (who in some statistically guaranteed proportion, will die based on this horrendous medical advice) suffer the consequences of their own bad advice. What sort of ethically depraved person would do such a thing? I don’t wish for such people to die but I do think they deserve to get a scary bout of COVID. That may sound cruel but it is not, it is the foundation of justice, that those who issue terrible advice should have enough skin in the game to first experience the consequences of their advice/actions before others do.
I’m GLAD Trump got COVID. Because I wanted him dead or to suffer? No, because I wanted him to shut his goddamn yap and stop harming people who listened to him out of loyalty. A lot of those people are dead and even now, dying. Trump NOT giving bad medical advice is a good thing and if the only thing to shut him up or teach him not to do that is to get a dose of karma/justice and overcome his lack of empathy and hypocrisy, then that is a good thing for US citizens. It’s an ethical position, not to be confused with finding humorous when people who are ignorant, gullible, cavalier, risky, apathetic, or misinformed contract or even succumb to COVID. So don’t get it twisted.
Still don’t buy it? Imagine being that person who would willfully advise others to endanger themselves, whatever their motives. I’ll go Hitchensesque here…those people deserve our contempt and ridicule and deserve to be muted and if they suffer the consequences of their bad advice, good…it’s not only ironic but just and I would hope that they take responsibility like a proper adult should and learn a valuable life lesson.
I’m just gonna leave this… sorryantivaxxer.com
It’s more likely for ivermectin to make a horse fly than for Bret & Heather to apologize or admit they were wrong about anything really.
What in the world happened to them, anyway? Their devolution into serious crankhood was rapid indeed. I listened to a few episodes of “The Dark House,” but soon realized something had gone cognitively wrong and stopped.
I fully expect that the widow’s position (or that of any number of idiots speaking on her behalf) will be that the ivermectin WOULD HAVE saved him, but for the delay in his getting it caused by the litigation.
Responding to that would be like trying to nail Jell-O to a wall.
I think you are entirely correct. This incident will only reinforce the ivermectin good, vaccines bad, it’s all a evil conspiracy attitudes of those already inclined in that direction.
A month or so ago when we met for lunch a long time friend (since HS) who in more recent years has not come across a conspiracy theory he doesn’t believe said to another friend who admitted to being vaccinated, “Oh no! They got to you didn’t they!”
I’ve about lost hope.
People in my very red state of South Carolina are so on board with Ivermectin. I went to my “female practitioner” midst the pandemic regarding hormone issues. She stated that everyone in the office who caught Covid had been successfully treated with ivermectin. I haven’t gone back there.
ALL drugs have side effects. How can anyone dismiss a vaccine because of side effects and take something else even though that has side effects also? I don’t think I’ll ever hear a logical answer to that one.
This is one aspect which puzzles me very strongly. We have effective vaccines from Pfizer/BioNTech, Moderna, J&J or AstraZenca, all of which normally have only mild side effects after injection. But vaccination opponents insist on treatment with (most probably ineffective) Ivermectin or hydroxychloroquine, all of which have significant side effects.
Heck, even a widely used mild pain reliever like aspirin has a long insert describing many undesirable drug effects, that can be very dangerous for patients.
Not to mention the little blue pills from Pfizer that some gentlemen consider very important to their lifestyle.
Is it just me, or do you also get the sense that they are fans of Ivermectin because they are wary of vaccines? “We don’t need your stinking preventative, we’ve got treatment options!” Of course this doesn’t explain why they pass over an actually effective drug in favor of a wildly speculative one…
Yes, stupid can kill you sometimes. I saw an article in the Post today from Minnesota hospitals pleading with people to get vaccinated. They are maxed out in the ICU and have no more beds. I believe they said the vaccinated in the state is at 64%. That makes for a lot of sick people.
Weinstein and Heying disappoint me the most in all this Ivermectin stuff.
The nation’s undisputed dumbest US senator, Wisconsin Republican Ron Johnson, has touted mouthwash as an effective
breath freshnerSARS-CoV-2 antiviral.Such is the quality of representation in what was once known as the world’s greatest deliberative body.
On the hypothetical, there is the possibility that such a thing (along with maybe an OTC nasal spray of some sort), could temporarily retard the virus from latching on.
No doubt she will soon sue the hospital claiming they are at fault. America’s health care professionsals when the courts back anti-vaxxers: damned if they do, damned if they don’t.
I certainly feel bad for Kevin, Darla, and their families. But a big shout-out to that hospital and medical staff in general. You all do an incredible job under difficult conditions on any normal day, and now under impossible conditions when the courts side with anti-vaxx madness.
+1
It would not surprise me that the ivermectin believers will build up a strong immunity against taking the new Pfizer pill.
For a painfully deep dive into published research on Ivermectin, see this: https://astralcodexten.substack.com/p/ivermectin-much-more-than-you-wanted.
TLDR:
“Ivermectin doesn’t reduce mortality in COVID a significant amount (let’s say d > 0.3) in the absence of comorbid parasites: 85-90% confidence.
Parasitic worms are a significant confounder in some ivermectin studies, such that they made them get a positive result even when honest and methodologically sound: 50% confidence.
Fraud and data processing errors are of similar magnitude to p-hacking and methodological problems in explaining bad studies (95% confidence interval for fraud: between >1% and 5% as important as methodological problems; 95% confidence interval for data processing errors: between 5% and 100% as important).”
Very interesting. It explains the difference in the results of ‘good’ studies by looking at endemic worm infections. This is really a promising direction.
It’s all over the pandemic research. Science has an article (which can and should be criticized) that criticizes weak studies. On studies of handwashing, mask wearing and physical (not social) distancing as evidence based measures:
“‘It’s misinformation at worst.’ Weak health studies can do more harm than good, scientists say”
So these things – outside of hospital use – are not evidence based medicine and not a basis for policy decisions. They may become, but not at this rate.
The missing link: https://www.science.org/content/article/it-s-misinformation-worst-weak-health-studies-can-do-more-harm-good-scientists-say .
Several months ago I read the FLCC’s (the Ivermectin pressure group) own meta-analysis of Ivermectin.
Even taking it all at face value and ignoring any problems of bias and data quality, it was very clear that their positive conclusions were heavily driven by just two of the trials (the Elgazzar being one) and the observational data.
My conclusion was “worth looking at properly, but so far no evidence that it has much/any effect”.
Interestingly Merck … a manufacturer is not (as yet) recommending Ivermectin for COVID. They are awaiting data, the sane viewpoint.
https://www.merck.com/news/merck-statement-on-ivermectin-use-during-the-covid-19-pandemic/
Ivermectin is an outstanding drug in Onchocerciasis, aka river blindness, mainly in West Africa. The vector is the ‘black fly’. Whole areas were inhabitable due to this disease.
Ivermectin has prevented hundreds of thousands from going blind. It infests the cornes as well as the optic nerve and sometimes retina (A colleage of mine working in West Africa indeed called it a miracle drug) generally given in combination with steroids and doxycycline The steroids to reduce the inflammation, which may persist even when the worm is dead, and doxycycline (a tetracycline antibiotic) to combat a symbiont (the Wolbachia bacterium) upon which the worm Onchocerca volvulus appears to be dependent.
So yes, Ivermectin is a miracle drug for river blindness.
However, during the 3rd Covid wave our ICU was predominantly populated by unvaccinated on Ivermectin. Hence I have some serious doubts about its efficacy in Covid.
With regards to the long article by Alexander Scott linked to by Robert Knapp, under 11 above, I come more and more to the conclusion “How stupid of me not to have thought of that myself” .
After singing the blessings of Ivermectin as a dewormer, I must have been blind. Why would Third world studies show a significant benefit of Ivermectin? While in First word studies it does not? Endemic worms that reduce our defences against Covid.
It is so obvious as to be perverse. Did some predjudice against Third world studies make me biased, clouding my judgement? I’d like to think not, but I’m not sure.
There WAS some preliminary data at the beginning of the pandemic that suggested that ivermectin might be a potential candidate for treatment of COVID. Turns out that data was pretty rotten and subsequent studies show little to negative benefit.
But just because a compound has an approved use that has nothing to do with viruses does not always mean it would necessarily not have any utility against COVID:
https://www.nature.com/articles/d41586-021-02988-4#:~:text=Fluvoxamine%20is%20both%20inexpensive%20and,COVID%2D19%20from%20turning%20severe.&text=A%20cheap%2C%20widely%20available%20drug,to%20clinical%2Dtrial%20results1.
The linked article mentions that the patient’s vaccination status is unknown. That makes it sort of unfair to characterize this as being about using unproven treatments instead of the vaccine.
If I had a family member in hospital, and had been informed that survival was unlikely, and that all known treatment methods had been exhausted, I might well suggest Ivermectin myself.
There is no particular risk, and the cost is near zero. Short and long term risks are well known, and the drug is readily available.
Of course, I have no idea how effective it is. There are places that use it very freely which have very low infection rates, or at least report that this is the case. I have not heard about any place where it is used on a large scale but infection rates rose disproportionately.
If you seek expert advice about, as an example, the claims coming out of Utter Predesh, you get this sort of tortured language-
“There is no peer-reviewed randomized control study that shows that ivermectin is the reason why cases are going down in Uttar Pradesh”
The above statement is factually correct. The same expert mentions later that other measures, such as promoting mask wearing might be responsible for the drop in cases.
Once again, I don’t know if it helps or not. I do know that Merck and Pfizer are not primarily humanitarian organizations. There is a history of them putting profits above any other concerns, even when doing so involves illegal activity or patient harm.
The amount of money involved with the vaccines and the newly proposed pills is almost unimaginable.
Just as an intellectual exercise, try to imagine their actions assuming Ivermectin is even partly effective. It is in the public domain, and already being produced in lots of places for 4 cents a dose. Certainly the companies that stand to make infinite amounts of money selling pills for $700 a course are not going to spend any money on Ivermectin studies. At a minimum, they would use whatever influence they have to prevent or discredit any such studies. It would make good business sense.
The reasons to oppose unconventional treatments are, in normal times, to stop people from using them instead of proven treatments, to keep charlatans promising miracle cures from fleecing the patients, and to prevent people from taking harmful and unproven cures.
In the case under discussion, there is no further treatment or likelihood of survival.
There is no money to be made on a treatment that costs less than sudafed.
The risks to the patient are essentially zero.
The backlash against Ivermectin seems very much disproportional to the risks involved. Some docs promoting it do seem to be kind of sketchy, but there is another group of docs who are quietly using it in addition to more conventional treatments, as well as endorsing vaccinations, social distancing, and the rest. Once someone is in the hospital, the time to get vaccinated is past.
A good message would be that anyone promoting Ivermectin as an alternative to conventional vaccines and treatments is wrong, but it makes no sense to demonize anyone even suggesting the possibility of it being effective. The disease itself is just too new to have a long-term body of effective treatment methods.
Merck are not promoting the use of Ivermectin for COVID.
The issue is not vax plus other, but other instead of vax
Merck no longer holds the patent for Ivermectin. Of course they are not promoting it. They are promoting their new drug molnupiravir, which costs $700 for a five day course.
I am sure it differs in many ways from Ivermectin, but there is no real way to know.
When someone is in the hospital, and about to be put on a ventilator, vaccination is not one of the options. Some of those people facing that treatment are fully vaxxed and boosted. The pushback from the government and hospital systems against Ivermectin is so strong, one might assume the patients are asking for the whole ward to be dosed with Sarin gas.
There is just an unreasonable amount of anger and emotion on this subject. I would expect the patents and their families to be emotional, because to them it is a matter of life or death. It seems odd that those outside of the families are so very angry about this.
It is of course anecdotal, but a decent number of people in that situation have been treated with Ivermectin by their doctors (real qualified doctors) and have made fairly quick recoveries.
When enough time has passed, it is reasonable to expect that the data will be there to know exactly what works best in the long and short term. Until then, treatments will continue to evolve.
The reason that happens, is that docs try different things, and relate what seems to work to their colleagues.
The court cases popping up in the news are not about vaccination. They are about people in hospitals for whom the conventional treatments do not seem to be working, and want to try something else that is not going to do any harm, and will not add to the cost. Other hospital systems use Ivermectin routinely as part of Covid treatment. If there appear to be benefits and no serious side effects, them doing so should not generate so much anger from those not directly involved.
Nobody is going to come out of the hospital after such a treatment and say that they are glad they did not get vaccinated.
“I am sure it differs in many ways from Ivermectin, but there is no real way to know.”
It’s pretty farfetched they would try to pass Ivermectin off as a new drug i would think. That should be sufficient to be a real way to know.
I have for many years listened to my wife complain that the drug companies spend a great deal of money producing slight modifications of drugs that are going generic, in order to patent the new formula that they can sell at a higher price. Then they do what they can to discredit to old one, and go to great effort to get physicians to prescribe the new, very expensive drug.
I have no evidence that this is the case here. Or that it is not. But it is a key element of their business model.
I am not claiming that they are either all good or all bad. They produce lifesaving products that extend our lives and make them better. Yet they have been guilty of putting profits before safety on many occasions. They have been found guilty of fraud, of concealing safety issues with their products, paying kickbacks to get their drugs prescribed, and with arbitrarily raising prices on lifesaving meds for no reason other than to raise profits. They are no more or less moral than Dow or Union Carbide.
The potential profits for Covid treatment are almost unimaginable. With that much at stake, it is prudent to maintain at least a healthy skepticism at the motives and actions of those companies.
You do know that almost everyone treated with nothing but tender loving care makes a quick uneventful recovery from Covid. If only a “decent number” of Covid patients recover “fairly” quickly with ivermectin, I could posit that ivermectin is making them worse. (I won’t, because I don’t like to be gratuitously antagonistic.)
The buzz around ivermectin is that you take it as soon as you get sick. At that point, the testimonials will look good because most people will recover anyway. If someone crashes despite taking ivermectin, mum’s the word.
Any true believer who recovers from serious illness after taking ivermectin will ascribe his recovery to the drug and ignore the $50,000 worth of other treatments he got. That’s just how people are.
That’s why we need RCTs.
It is nonetheless true that it is difficult to get Pharma to sponsor clinical trials of drugs that other people invented or that other people can sell if the study is successful. They are mostly interested in their new drugs. But Pharma is not the only source of funding for good questions. Dexamethasone was the first drug to show benefit in severe Covid. It has been off patent for many years. Both trials of fluvoxamine, an antidepressant, were done without industry funding, as was colchicine. Other than dex., none of these repurposed drugs have been dramatically effective — colchicine wasn’t at all — but they can still get studied.
“I am sure it differs in many ways from Ivermectin, but there is no real way to know. ”
That is laughable. It is a protease inhibitor. The structure is given right here in this Science paper that discusses the synthesis, the basis for selecting the final structure (solubility, ease of synthesis), safety studies, etc.
Just because you don’t know something doesn’t mean that the information doesn’t exist.
Thank you for pointing that out. I will force one of my kids to read it and explain it to me in terms a non-chemist can understand.
The Wikipedia page on Paxlovid is probably more digestible. However, at the end as it is currently written, the assertion that ivermectin is also a protease inhibitor is at best very misleading. While the stuff may inhibit proteases, it does so only in great amounts. What it does do well is inhibit its target chloride channels, and that’s why it is effective against river blindness. There is no targeting of any protease involved in ivermectin’s mode of action there.
“Nobody is going to come out of the hospital after such a treatment and say that they are glad they did not get vaccinated. ”
You would be surprised.
Ivermectin is the opium of the anti-vaxxers. 😎
“The reasons to oppose unconventional treatments are, in normal times, to stop people from using them instead of proven treatments, to keep charlatans promising miracle cures from fleecing the patients, and to prevent people from taking harmful and unproven cures.”
First, the man’s vaccination status is unknown only because the widow refused to disclose it. Given that he’s described as a “devout christian”, a group with high vaccine refusal rates and that there’s no reason to hide that he received the vaccine in the first place, this seems like a typical antivaxxer story; he declined a proven treatment and his wife fell back on an unproven cure.
Second, the group advising her certainly come across as charlatans promising miracle cures. You can search yourself for FLCCC Alliance. Make sure to check out their disclaimer page, it’s a real doozy.
Third, no money to be made? The most prominent of these groups, America’s Frontline Doctors, has made a reported $6.7 million in medical advice and another $8.5 million in prescriptions. Seems like a pretty profitable business for telemedicine. In this woman’s case, the hospital did not administer the treatment, she had to hire a private doctor. I’m confident he charged more than the cost of a sudafed.
It’s odd that you perfectly describe why people are opposed to the use of Ivermectin, then conclude that this isn’t what’s going on.
A brief addendum to this story, although we’re past it by now.
According to sorryantivaxxer:
https://www.sorryantivaxxer.com/post/keith-smith-52-york-pa-engineer-pro-ivermectin-dead-from-covid-despite-ivermectin
The deceased did contact America’s Frontline Doctors, was prescribed Ivermectin, purchased it from them, but never received it.
So it does appear that charlatans fleeced this patient.
Darn! I was hoping your title was reporting on the RCT of ivermectin. Hey, I wouldn’t be surprised to read it here first. Of course the believers will remain convinced that had Mr. Smith been allowed to take ivermectin earlier, when he wanted to and not when the Court allowed him to, it would have saved his life. That’s how special pleading works.
Sad that the PRINCIPLE RCT will be a waste of resources, at least the arm that is looking at ivermectin. RCTs are designed to test the ability to reject a null hypothesis that an intervention is useless. Without belabouring statistical principles, merely failing to reject the null hypothesis does not prove the null is true, only that the effect, if any, is likely (at some beta level, usually 0.8 in medical studies) to be smaller than the trial was powered to detect. The smaller the effect size you want to avoid missing, the larger and costlier the trial has to be. And no matter how large, the zealots can always attack your “negative” result as still not large enough to pick up some small effect that they passionately believe in. (“If it saves even one life….!”) This will especially be the case if the “raw score” favours ivermectin, like a basketball score of 110 to 109. And they could still insist that even an infinitely large trial was faked to suppress The Truth.
It is hazardous, on Bayesian grounds, to do RCTs for a treatment that seems unlikely to be useful in the first place. The likelihood that a “positive” trial is false, even if well done, rises sharply if the pre-trail likelihood of true benefit is low. A trial that tests a treatment for which there is very little a priori evidence of efficacy needs to be unduly large both to reject small true efficacy and to avoid the consequences of a type 1 error of falsely rejecting the null. The resources for an ivermectin RCT should be spent elsewhere….and may end up being so given the difficulty in sourcing the drug and getting potential subjects to consent to randomization.
For my money, the meta-re-analysis of the high(er) quality trials of ivermectin settles the issue, despite its own problems. It’s so unlikely to be beneficial that if I had Covid I would not consent to join the ivermectin arm of the PRINCIPAL RCT Some of the excluded trials remind me of the aluminum foil chaff that is dispensed from aircraft to confuse radar systems.
(If you are harbouring the intestinal roundworm Strongyloides stercoralis which is endemic in Africa you might want to be given ivermectin (or other worm-icide) to prevent fatal hyperinfection before you start taking dexamethasone for Covid. This might conceivably explain why ivermectin looks better in populations where this worm is common….but the treatment is still for worms, not for Covid.)
My, medical statistics must have changed a lot since it was part of my statistics training. My professor (specialising in small-group evaluation of treatment for rare cancers, where getting a half-dozen patients into a trial was a major hurdle) was always most insistent that for any disease that has ever been treated before, your trial is always going to be be against the best available treatment for the disease, because you’re looking for a better treatment than the existing one(s).
Plus, of course, if there is a treatment available, the institution’s Ethics Board would probably have things to say about offering some patients a random chance of “no treatment” for a disease where there is already a treatment with a known (even if poor) prognosis. Those “things” would likely start “N”, end “o” and be two letters long.
Modern Ethics Boards must be very different to the 1980s.
Other than your first and last sentences, you are correct. But nothing I said, including what you quoted, contradicts that. Null doesn’t mean no treatment. Nobody in an RCT gets “no treatment”.
All ethical RCTs compare the novel drug (or other intervention) plus the best known standard treatment against the best known standard treatment alone. The subjects randomized to the “standard” arm should receive an inactive control substance to mask them and the investigators as to who got what, to avoid biasing assessments of outcomes. These inactive substances are usually still called placebos, a inappropriate use of a word which unfortunately became deeply rooted in the early days of clinical trials.
The null hypothesis in an RCT is that the novel treatment adds no net benefit to best known standard treatment, i.e., it is useless. Significance testing in a human trial must always be two-sided, to detect the real possibility that the novel treatment is harmful, not just useless.
More problematic are RCTs whose design requires that subjects randomized to receive the investigational treatment must forego some part of the best known standard treatment in order to receive the investigational treatment. For example, consider a trial comparing surgery within an hour to immediate use of “blood thinners” or “clot busters” for a certain type of heart attack. If a subject is randomized to surgery he can’t have a clot buster while the surgeon is pulling on his trousers because he might bleed to death during surgery. So until you know that surgery without clot busters is better — that’s what the trial is trying to find out — you have to deny to the “surgery” subjects a treatment that is already known to be effective in heart attack.
The biggest question for the Ethics Review Board asked to approve such a trial will be, What is the pre-trial likelihood that surgery will indeed turn out to be better over-all than clot busters? This has both scientific and ethical dimensions. If it is judged by expert peer review to be high and if the question is important to patients to find out for sure — clot busters can be fatally dangerous even without surgery; we’d love to do away with them — then the trial will likely get the green light. In real life it did and the standard of care has changed to immediate surgery (angioplasty) with no clot busters, if it can be done within an hour (or so, in real life.)
Plus, of course, all the other elements of the best standard treatment for heart attack.
Good article but this is exactly what a vaxxer would say, right? 😉
Reddit has its “Herman Cain Award”. Sadly, there are hundreds of examples of suicide and manslaughter through stubborn ignorance similar to the one given here at WEIT.
https://www.reddit.com/r/HermanCainAward/
Maybe Bret Weinstein and Heather Heying should win the Darwin’s Shame Award – a humiliating trophy for issuing advice so bad that it convinced others into winning an actual Darwin Award.
Or maybe they should take the Hypocritic Oath: the promise to cause harm to others if they stand to benefit thereby.
If you steadfastly refuse to get vaccinated for any of the usual antivaxx reasons and wind up dying from COVID, I really DO NOT CARE. I’m not happy, but I really don’t care.
What I do care about are the people you needlessly exposed to the virus while you were getting infected, and I especially care about the people that you have burdened in taking care of you. I know some of those caregivers, and they tell me the same things as this doctor in Michigan says. Plus, you are taking up facilities that might be needed for the sorts of cases that otherwise come into hospitals. Also, to some degree still now may be keeping people away from a hospital for treatment for other things. I know of one guy in the pre-vaccine period who needed heart surgery but he was so afraid that he’d catch COVID and die that he stayed home and died of his heart condition.
One of the outcomes of these scenarios particularly in rural areas will I think be that it will be even harder to attract doctors to those areas.
Sweden took a very bad mis-step initially in not promoting social distancing, but they learned. My Swedish mentor’s son, an anesthesiologist, told me a couple days ago that the vaccination rate there is now 80% and that the ICU’s still see a few COVID patients, but that the situation there now is entirely manageable.
Prof Coyne is right, avermectin is highly unlikely to result in a statistically significant reduction in mortality from COVID or even a reduction in hospitalization, disease severity, or symptoms. But let’s say that the current clinical trial of avermectin actually did show some benefit to COVID patients. It is insanely unlikely that it would come anywhere near the 89% survival efficacy of Pfizer’s oral drug that was designed specifically to inhibit a key coronavirus enzyme required for its replication. There’s no way avermectin will match that (or we would already definitively know that by now) and therefore is undoubtedly an inferior drug. In clinical research, an inability to show superiority to existing drugs (with human data) means that the FDA won’t approve it for that disease unless there’s some other benefit to a specific cohort of patients. Avermectin could still be prescribed by a doctor for COVID patients “off-label,” meaning some patients could still get it even though the FDA did not approve the drug for treating COVID specifically.
In short, stop the avermectin trial, they’re probably wasting their time. The best option will likely be for Pfizer and Merck to combine their oral drugs to hit the virus on three different fronts simultaneously such that not even natural selection can mutate those proteins fast enough to evade death. This is how the pharmaceutical industry defeated HIV and more recently, cured chronic hepatitisC infections.
I agree. Although there is a possibility that ivermectin does reduce the impact on some COVID victims… those who have internal parasites which weaken their immune response. Ivermectin does it’s normal thing, kills the parasites, and enables a stronger immune response to COVID. This would go some way to explaining why Ivermectin seems to ‘work’ in the populations of the Third World, and doesn’t appear to work in the First World.
Yes, read the great article by Alexander Scott that Robert Knapp linked to above, under 11.