Guest post by Alec Rawls
For weeks Dr. Anthony Fauci has dismissed all of the mounting evidence for the efficacy of Hydroxychloroquine treatments for Covid-19 as “anecdotal” and “the slightest hint of evidence” because it doesn’t come from clinically controlled trials. That is just wrong. Valid statistics do need a control group but the control does not have to be clinical.
New York alone has recently amassed many thousands of case histories of Corona patients who were given various HCQ treatments (HCQ plus zinc and/or Azithromycin in various dosages) as doctors swapped information about what seemed to be working. Despite the lack of a clinical control group (doctors are not withholding what they estimate to be the best medicine from half of their gravely ill patients), there still is a massive control group in place: the hundreds of thousands of case histories of Corona patients all around the world who never received any Hydroxy treatments.
The outcomes from large samples of both groups just need to be tallied and the statistical significance of the difference in mortality will far exceed what could ever be achieved through clinical trials (unless the CDC is planning on killing an awful lot of people by withholding already known to be life-saving medicine from them).
But Dr. Fauci has no plans to look at this huge body of field data. He plans to wait instead until clinically controlled trials are completed sometime this summer. From April 9th:
It’ll probably be months, sometime in the summer—we’ll start to see which are working, which are not and to focus on those that are we developing and will work.
Forget the fantastic progress that hundreds of doctors working feverishly on thousands of patients have already made in discovering “which [treatments] are working and which are not.” What’s the hurry? We’ll just re-invent the wheel.
Denigration of trials that use non-clinical controls is a 180° turn for Dr. Fauci
It turns out that Dr. Fauci knows as well as anybody that non-clinical control groups support perfectly valid statistical evidence because his own career-making medical research was entirely dependent on historic controls (comparing his treatment outcomes to historic mortality rates), with no clinical control groups ever involved.
This bit of Fauci history was mentioned by Dr. Stephen Smith in an interview with Laura Ingraham on April 6th. Ingraham asks what Dr. Smith thinks about Fauci’s skepticism and he responds:
What he’s saying Laura is that we don’t have randomized controls of the trials and that’s true but we have plenty of diseases including the disease that doctor Wolff and Dr. Fauci [unintelligible] got famous for: Wegner’s Granulomatosis. They developed a treatment for it in the 70s and 80s that saved lives. But if memory serves their article in Annals and their article in 1973, Annals [was] in 1983 I believe, they didn’t use, it was not randomized, it was not controlled. They didn’t even have contemporaneous controls, they used historical controls, and I’m not blaming them. I believe they did great work and that the treatment DID work.
But we use the data we have, and then we build up on experience. Now the experience that we have had treating patients with a combination of Hydroxychloroquine and Azithromycin is that the data accumulated, and if you get to it, the more you are on it, the lower your chances of being intubated or being on a ventilator are. Those are observational data but very very powerful data.
Dr. Smith is right, Fauci’s own medical research is rife with non-clinical controls
Here is a 1973 article that Dr. Fauci wrote on Wegman’s Granulomatosis with a Dr. Wolff (abstract, full text):
FAUCI AS, WOLFF SM. Wegener’s granulomatosis: studies in eighteen patients and a review of the literature. Medicine (Baltimore). 1973;52:535-61.
On p. 551 they use a pair of past studies to establish a baseline mortality for the disease they are trying to treat:
They found that the average time of survival of these patients was 12 ½ months as compared with the untreated patients in Walton’s review (106) where survival was 5 months.
106. Walton. E.W.: Giant-cell granuloma of the respiratory tract (Wegener’s granulomatosis). Brit. Med. J., 2: 265. 1958.
Ten years later in January of 1983 The Annals of Internal Medicine published another Fauci-Wolff study (abstract; full text):
Wegener’s Granulomatosis: Prospective Clinical and Therapeutic Experience With 85 Patients for 21 Years
ANTHONY S. FAUCI, M.D.; BARTON F. HAYNES, M.D.; PAUL KATZ, M.D.; SHELDON M. WOLFF, M.D.
For the mortality of an untreated control Fauci, Wolff et al. cite in this 1983 paper the same Walton review article they cited in their 1973 paper:
The mean survival of untreated Wegener’s granulomatosis was 5 months with 82% of patients dying within 1 year, and more than 90% of patients dying within 2 years (9).
9. WALTON EW. Giant-cell granuloma of the respiratory tract (Wegener’s granulomatosis). Br Med J. 1958;2:265-70.
Of course using a historical control is perfectly sound science. It is just 180 degrees opposite from what Fauci is for some reason insisting today, and the change is definitely recent.
Googling Fauci “historical control” also brings up from the New England Journal of Medicine a November 4th 2016 Fauci etal. abstract that concludes:
VRC01 slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week 8.
So at least until November 2016 Fauci was fine with historical controls.
The CDC and Fauci’s NIAID are shirking their immediate responsibility to tally the massive existing field trial evidence
Dr. Fauci’s pretense that non-clinically controlled trials are unscientific keeps our public health bureaucracies from taking up their most immediate responsibility. Fauci is the head of the National Institute of Allergy and Infectious Diseases (NIAID). His group and the CDC are the ones who ought to sending a small part of their large federal workforces to New York and around the country to compile the massive number of existing case-histories into a data set that can be analyzed.
From the CDC’s mission statement page:
CDC in the 21st Century – confronting global disease threats through advanced computing and lab analysis of huge amounts of data to quickly find solutions.
Except they are not interested in collecting the already existing data that can quickly provide an accurate assessment of how much the HCQ treatments lower mortality for at-risk patients. Their official position under the guidance of Fauci et al. is that real-world data isn’t good enough to bother with. Instead they will wait until they can generate their own clinical data.
Listen to CDC chief Dr. Robert Redfield dismiss evidence from field trials about the effectiveness of HCQ treatments (at 1:10 here):
Yeah, I’m not going to recommend it and I’m not going to not recommend it. I think that you and I are very similar. We’re probably similar to my friend, Dr. Fauci. We-we-we we’re very comfortable to responding when we have data.
He is following Fauci, refusing to regard field trials as having statistical significance. Because field controls are not clinical they supposedly produce no “data.” These are the heads of the two bureaucracies that need to be out processing this data and they both at least claim to believe that real-world data isn’t actually data.
We might have a substitute for social distancing in eight days
In his initial interview Dr. Smith spoke to this perverse phenomenon of health bureaucrats badmouthing the attempts of doctors in the trenches to tell each other and the world what is working for them. Instead these agencies ought to be coming in to collect and process the field data for themselves.
Here is what Smith said about Fauci denigrating the early French study as “anecdote”:
The French had the virologic study first. I think that was March 17 maybe? They showed that if you used these two drugs together [HCQ + Azithromycin] the patients stopped shedding virus, or cleared virus, by day six. American researchers — I’m a private practicing I.D. Doc [Infectious Disease] — If American researchers were worried about that [about the validity of the French findings] they could come up here to New Jersey and have that study done in eight days. I don’t understand the hand ringing. I don’t understand the hesitation. If you’re worried about getting studies done, do them.
Yes, and if steep drops in the level and duration of viral load is borne out it means we have a way to dramatically lower Corona transmission rates independent of social distancing and economic shut-down. Just ask everyone who gets flu-like symptoms to drive through for a Corona test and if they come up positive give them 5 days of Hydroxy and zinc, then we can all get back to our normal lives tomorrow.
But getting this crucial information in eight days doesn’t interest the CDC and NIAID. They only consider clinically controlled trials to be meaningful (at least since November 2016), so they aren’t going out and running virology tests on patients in the field. Neither are they collecting the existing patient data from Dr. Smith’s practice and a hundred other New York area practices and a thousand other practices around the country. What actually happens in the world is not evidence as far as they are concerned.
Doctors in the trenches are doing what bits they can of the data analysis that our AWOL CDC and NIAID should be doing
With Fauci and Redfield refusing to let NIAID and CDC do their jobs it gets left to the overworked doctors in the trenches to tally the small chunks of data from their own practices, yet even those small chunks of data show great therapeutic efficacy of strong statistical significance.
Smith says that his treatment results can be analyzed as an inter-cohort control. Out of 72 very sick patients the 20 who he had to put on ventilators had all been on Hydroxy treatments for two days or less. None of the patients who had done a full five day treatment went on a ventilator. His amateur statistician sons tell him the probability of that result being chance instead of a product of the treatment is “point zero, zero, zero, something.”
Assuming the CDC would want a more professional estimate Dr. Smith invites the CDC to come do its job and analyze his data for themselves.
“Point zero, zero, zero something” is pretty good but the CDC could really drive the uncertainty down by pulling together the case histories from hundreds of such practices.
Dr. Zelenko, an hour to the north of Dr. Smith, is up to 911 patients. As part of his ongoing effort to get the word out about the success he is having with his HCQ + Azithromycin + zinc Coronavirus treatments he tallied his own numbers in this April 4th YouTube video:
Zelenko (at 12:20): Now let’s do some statistics. Depending on which country you look at the mortality rate in the high risk patients is between five and ten percent. We’re an advanced country so let’s take the lower number of 5%. Out of those 350 patients [the number of Zelenko’s patients who he categorized as high risk] we statistically should have seen 17 dead people and a multiple of that on respirators. What did I see? Zero dead people and only three people on the respirator.
Set aside the exact statistical significance of that finding. If a full tally of all the case histories in all the practices in the New York area show similar reductions in mortality and morbidity the statistical significance/certainty of that finding will be extreme. Get it done. In the meantime Zelenko’s quick and dirty estimate is telling in itself.
Is a well controlled 1061 patient sample still “anecdote”?
Doctor Didier Raoult, the French doctor who Fauci originally discounted for running a small non-clinically controlled trial, just released a larger non-clinically controlled trial. For his control group Raoult used “patients treated with other regimens both at IHU and in all Marseille public hospitals,” which is a lot closer to Raoult’s treated-patient population than the control that Fauci used for his own research.
Raoult’s new trial involved 1061 patients and examined the effects of early intervention. His conclusion:
The HCQ-AZ combination, when started immediately after diagnosis, is a safe and efficient treatment for COVID-19, with a mortality rate of 0.5%, in elderly patients. It avoids worsening and clears virus persistence and contagiosity in most cases.
That’s the Case Fatality Rate, not the Infection Fatality rate, which is probably an order of magnitude lower. IFR for a normal flu is about .1% so the IFR of Corona when Raoult’s treatment is used should be about half that, and that is in elderly patients who have the highest Corona fatality rates.
Clinical trials don’t even know what to look at without field experience on what works
Some doctors, like Dr. Cardillo in Los Angeles, are finding that HCQ treatments are more effective with the zinc. Is the CDC planning to drag out its clinical trials by running separate trials for all the different drug combinations and dosages being tested now by doctors in the field?
They should do that, just don’t make us wait for it. Tally the field data now. It already exists and is perfectly adequately controlled and it has the numbers to yield a high level of statistical certainty.
The CDC and NIAID need to do their jobs and get on this. It is dereliction of duty that data compilation and analysis is being left for doctors in the trenches to pick up piecemeal.
For whatever reason Fauci and Redfield don’t want to analyze real world data. They need to be fired (if not court-martialed, to employ President Trump’s war metaphor) and replaced by people who will get the job done instead of blocking the job from getting done.
Only a very dishonest person can pretend that statistics are not valid unless they are based on clinical controls, which makes it not so surprising that the leading proponent of this claim is someone who professed the exact opposite until November 2016.
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Fauci needs to go urgently for the future survival of the USA. Trump needs to fire him immediately he must not have no input to any health decisions in the USA. look at what happening in Michigan NOW the people have had enough! https://www.youtube.com/watch?v=sGTpUISRv8A. this is a normal virus look at Willis graph all countries including Sweden are showing normal metrics this is just a normal flu vuris that has been exagerrated that kills millions of old peolple every year. Mockton is way wrong and Jo anne nova is is also. Applying these lockdowns will kill millions from starvation no jobs WILLIS IS RIGHT wake up before you are all in dire straights
Eliza
I think that the one thing factual about the situation is that people have strong opinions on what is happening, and the best course(s) of action. The problem is that it seems to be driven more by emotion than hard facts. I personally disagree with Monckton and Jo, but I respect that they hold positions on other things that I agree with, and they otherwise appear to have the ability to analyze difficult problems; however, they are human. I think that all would be served best if they give thought to what others say, and give the benefit of the doubt to those who have a history of wisdom, and reject the claims of commenters who offer only their personal opinions and no citations or hard facts to support their claims.
[Disclaimer: I have no hard facts to support the above opinion.] 🙂
+++++
Much, if not most, of the nastiness associated with this illness is iatrogenic in origin, IMO.
I think now you are getting around to your basic premise for your other loudly shouted beliefs.
“Wegman’s Granulomatosis ?”
Many of the commenters here have opined that any push-back against widespread use of hydroxychloroquine sulfate is some kind of liberal conspiracy, or driven by Big Pharma’s control over doctors. Consider this recent news reported by Fox News:
https://www.msn.com/en-us/health/medical/hydroxychloroquine-does-not-clear-coronavirus-but-can-alleviate-symptoms-study-says/ar-BB12FSC1
What about that should we consider? No drug clears virus. That’s the immune system’s job. If HCQ can stop or slow down viral replication so that people don’t have to be hospitalized it is a very successful drug.
icisil
You said, “If HCQ can stop or slow down viral replication so that people don’t have to be hospitalized it is a very successful drug.” Did you read the article before responding? The articles says that HCQ may address some of the symptoms. It says nothing about inhibiting replication.
Fundamentally, many commenters here are claiming that HCQ should be used by all infected at an early date to cure them. A conservative news service does not find that to be true.
Yes, I did read the article. One thing that’s not mentioned in the research is if they used zinc with HCQ. Zinc is antiviral, and HCQ is just the means of getting zinc into cells where it inhibits viral replication (I guess that’s what they mean by viral clearing?). If they didn’t use zinc then what good is their research?
So, IOW, anyone not getting zinc can be expected to have no benefit?
First it was chloroquine, then HCQ, then you needed to add Z-Pak. Now without the zinc the combo is worthless?
Viruses have been at biochemical war with the hosts they infect from millions of years.
But now we are to believe that zinc inside of a cell is all that is required to cure a viral infection?
Is it all viruses?
Because the theory with zinc does not seem to be specific to this virus.
Or is it?
Which is it?
Why do cells not have more zinc if that made them immune to viruses?
How much zinc kills a virus?
How much kills a cell?
And the research showing the ionophore effect was in chloroquine, but now proponents are saying it has to be HCQ.
Have you seen research that these are equivalent in terms of being an ionophore?
Where is this research?
Cells know how to make ionophores, so why have elaborate immune systems when a ionophore and some zinc makes cells immune to virus.
Or only this one?
Are all the original studies which started all of this fake because they did not use zinc?
What data are you relying on to think it is all so simple?
How much does 200 mg of zinc in a person put into each cell?
“A conservative news service does not find that to be true.”
1) Fox is not a conservative news. It’s mostly pro establishment. There is nothing “conservative” about trashing tariffs on China.
2) Even if Fox was “conservative”, whatever you mean by that, it doesn’t make Fox information about drugs any more credible.
3) HCQ should be used early according to Raoult, before condition of patients become too bad, before they need urgent care, before the virus overloads the person, before the virus load decreases by itself: on many extremely ill persons you don’t detect the virus, but they have been damages.
4) For any antiviral drug, and for all drug uses, time is key; you don’t allow a germ to replicate too much because then it might be too late.
HCQ is also used to reduce natural immunity, so if it doesn’t stop the virus replication, it might help the virus.
Thank you, have been saying this for weeks. Field trials are not anecdotes! Hundreds of thousands are dying! Unbelievable incompetence.
Note too that every year we inject tens of millions of Americans with *prophylactic* flu vaccines for which *no* effectiveness has been established at time of injection. And that’s just the flu!
The history of treatment assessment by individual physicians is pretty bad. One example is the use of diethylstibestrol for threatened loss of pregnancy. Its use continued for 17 years after it was shown in a double blind trial to be ineffective because, like all of us, doctors are overly influenced by the instances in which a positive correlation occurs – “I just knew she was going to lose the baby, but I gave her the stuff and got a beautiful healthy baby”. Years later an increase in a nasty breast cancer surfaced in young women, and was eventually tracked down to fetal exposure to DES; then testicular cancer in males exposed. There was also a lot of interesting research on the masculinizing effect in the girls – male activity and play, and also an excess of lesbians.
I’m sure I have seen previous comments on WUWT on Confirmation Bias as a trap in many different professions. I agree that collation of the data on chlorquine +/- zinc can give a better idea of its efficacy. But a whole lot of other practices are changing very rapidly as the pathology associated with WuFlu is worked out, so that historical controls will not be appropriate. For example, it appears that the red blood cell problem several above have referred to is actually a disseminated intravascular coagulopathy. In other words the cells are clumping up in the capillaries. WHen this happens in the lung, forcing in air just ruptures the alvioli. This means that the treatment needs to focus on anticoagulants before there is a disaster – I gather both heparin and other antiplatelet agents are being tried.
I have been in the middle of clinical medicine and biomedical research since I started translating for my father in a clinic in Orissa at the age of 4. On the basis of nearly 70 years of experience in and around medicine, I will withhold judgement about chloroqine +/_ Zn for a few more days at least.
I bought some shares in an Israeli start up that grew stem cells from placentas acquired after childbirth. Their tech had advantage of higher production compared to older methods. Watched the stock go through typical ups and downs and finally sold it couple of years ago at a lose. I sold too soon! Has tripled this week after some trials with a small number of very sick patients.
https://www.theweek.co.uk/coronavirus/106611/coronavirus-what-is-pluristem-s-placenta-based-cell-therapy
sign up and pass the word
2020 deaths aren’t any worse than the 2017-2018 flu season yet we’re all hostages now.
The unstated implication of the medical community lately is the deaths of those who died from COVID-19 could’ve been prevented, that the vast majority who died wouldn’t have died from their co-morbidities if they didn’t get COVID-19, as if all sick and dying people will recover and not die, a false hope.
COVID-19 is possibly a naturally produced exosome, falsely attributed as a virus (see video link below) that is a natural immune response to environmental irritants.
Dr Andrew Kaufman Rejecting CoronaVirus:
https://www.youtube.com/watch?v=BzRbq9XJ7mA
If he is right then forced reductions of these exosomes would weaken our immune system.
That video was removed by YT for violating community guidelines. It was going to go viral.
When I saw it on the 15th there were less than 180K views, a few days later it was almost 1M.
Then Cuomo came along a few days ago and claimed “facts are facts” and the vid disappeared.
Key point: “Clinical trials don’t even know what to look at without field experience on what works”
There is growing indication that CV19 attacks the blood/hemoglobin, which is a cause of hypoxia to various organs. My [limited] understanding is that this is why hydroxy chloroquine may work given the mechanical similarities to Malaria. Everyone is focusing on CV19 as if it is like the flu starting with the lungs, but the this virus works in more than one way. I know of a patient whose first symptom was anemia with a 50 year history of never being anemic. The cold symptoms and low grade fever started days later.
This is a great article, and summarizes my frustration well. We have enough data to draw conclusions. Why aren’t we using it? Like a lot of people, I want to know ONE thing right now. What do I do if I test positive? I don’t want to wait until I’m in the ICU to start treatment. Dr. Fauci, his organization, and the CDC have been absolutely useless in answering that question. This is with trillions of dollars at stake. They should have a recommendation, right now, based on the best available data. Instead it is a few individual doctors who have done the heavy lifting. What the hell good are they? If I was Trump, I’d fire the heads of these agencies and start over. If their only value in a crisis is providing bad models for the spread, we need to completely re-invent them.
“Chicago hospital treating severe Covid-19 patients with Gilead Sciences’ antiviral medicine remdesivir in a closely watched clinical trial is seeing rapid recoveries in fever and respiratory symptoms, with nearly all patients discharged in less than a week, STAT has learned.”
https://www.statnews.com/2020/04/16/early-peek-at-data-on-gilead-coronavirus-drug-suggests-patients-are-responding-to-treatment/
When this news hit the wires, the broader stock market indices rocketed higher in after hours trading.
There has not been one shred of bad news about this treatment, with the exception the disappointing but perhaps unsurprising reports that trials in China which began in April closed down and will not report results.
Many other hospitals and scattered patient reports emerging.
They all say about the same thing:
Some people who were not expected to live are walking out of the hospital within a day to several days, with few people who were not intubated needing to take the drug for more than 5 days.
Sorry, those China trials began in January.
No results are expected to be forthcoming from a single China patient although many got the drug several months ago.
I expect that China knew months ago how well this drug was working, and they covered up the info by closing down the trials.
Just published a few days ago apparently:
“Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency”
” Incorporation of RDV-TP at position i caused termination of RNA synthesis at position i+3. We obtained almost identical results with SARS-CoV, MERS-CoV, and SARS-CoV-2 RdRps. A unique property of RDV-TP is its high selectivity over incorporation of its natural nucleotide counterpart ATP. In this regard, the triphosphate forms of 2’-C–methylated compounds, including sofosbuvir, approved for the management of hepatitis C virus infection, and the broad-acting antivirals favipiravir and ribavirin, exhibited significant deficits. Furthermore, we provide evidence for the target specificity of RDV, as RDV-TP was less efficiently incorporated by the distantly related Lassa virus RdRp, and termination of RNA synthesis was not observed. These results collectively provide a unifying, refined mechanism of RDV-mediated RNA synthesis inhibition in coronaviruses and define this nucleotide analogue as a direct-acting antiviral (DAA).”
https://www.jbc.org/content/early/2020/04/13/jbc.RA120.013679.abstract
And reports from another hospital:
“COVID-19 patients in a clinical trial at Houston Methodist Hospital are responding quickly to the antiviral drug Remdesivir. The trial’s criteria allows for the treatment of patients early in their clinical course and, in some cases, at times where they might have otherwise been intubated.”
https://medicalxpress.com/news/2020-04-therapy-gaining-reputation-antiviral-drug.html
So the ethical guidelines that prevented the testing of Raoult protocol in Europe somehow allowed the testing of Remdesivir early? Or maybe rules differ between Europe and America?
The US Army:
“U.S. Army medical officials say they have successfully treated two soldiers diagnosed with the novel coronavirus, using an experimental antiviral drug designed to treat pathogens such as Ebola.”
https://news.yahoo.com/two-us-soldiers-covid-19-123141592.html
For those willing to read Pr Raoult’s, the French doctor, research results on HCQ/AZT Covid 19 treatment, they are available in Pre-print format on his hospital’s site.
He has now published a pre-print on a 1000+ cases cohort.
https://www.mediterranee-infection.com/pre-prints-ihu/
What is more certain in medicine than the link between radiation and human cancer?
Was it established by voluntary exposure?