Yale epidemiology professor Harvey Risch advocates use of hydroxychloroquine

Yale epidemiology professor Harvey Risch has been advocating for the use of hydroxychloroquine (HCQ) for the early, outpatient treatment of high risk Covid-19 patients. He has been criticized by Dr. Fauci, his Yale colleagues, and others. This is a link to his reply:

Why was he criticized by others? Here was the statement from his colleagues:

In his Newsweek article he cited two badly flawed studies and a Google document. It’s not that all the scientists and the FDA are against this drug because of X, but it’s because we don’t have high quality evidence of its efficacy. Very dishonest of him to dismiss the FDA as being bought out when the actual reason is the lack of evidence in randomized clinical trials.

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If you’re going to attack Dr. Risch’s paper, we should at least provide a link to it. It begins on page 45:

And Dr. Risch’s Newsweek piece:

So to summarize Dr. Risch’s reply:

  1. There are no RCTs of early treatment with HCQ of high risk Covid-19 outpatients.
  2. All inpatient RCTs of HCQ are irrelevant.
  3. There is no evidence of serious adverse effects from HCQ to Covid-19 patients.
  4. There is substantial retrospective evidence that early treatment with HCQ (in combination with other meds) of high risk Covid-19 outpatients significantly reduces hospitalizations and mortality.
  5. Therefore, the FDA’s refusal to grant an EUA for early treatment of Covid-19 high risk outpatients is unjustified.

Here’s another interesting article on the subject, this time from the American Association of Physicians and Surgeons:

Take-away quote:

Of the fake news and misinformation that has proliferated in this pandemic, the most harmful is the claim that hydroxychloroquine (HCQ) is a serious heart hazard. That incorrect claim has been supported by prestigious medical journals.

This negative message contradicts 65 years of experience of safe, worldwide use of HCQ for malaria, lupus, and rheumatoid arthritis. Hundreds of millions of patients have taken it without difficulty and without serious side effects. Recent studies in several countries have shown that if used early, within the first week of symptoms, HCQ is safe and highly effective for COVID-19.

That’s what I want to know. If hydroxychloroquine has been used safely worldwide for 65 years for the treatment and prevention of malaria, lupus and rheumatoid arthritis, how come it’s all of a sudden being denounced as dangerous?

Could we please discuss @Bilbo’s post on its own merits, and not on the basis of appeals to what else one does or doesn’t believe?

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This sounds like a professional medical association, but you should be aware who this group is:

The Association of American Physicians and Surgeons ( AAPS ) is a conservative non-profit association founded in 1944. The group was reported to have about 5,000 members in 2014. The association has promoted a range of scientifically discredited hypotheses, including the belief that HIV does not cause AIDS, that being gay reduces life expectancy, that there is a link between abortion and breast cancer, and that there is a causal relationship between vaccines and autism. It is opposed to the Affordable Care Act and other forms of universal health insurance.

The association’s Journal of American Physicians and Surgeons ( JPandS ), from 1996 to 2003 named the Medical Sentinel , is not listed in academic literature databases such as MEDLINE/PubMed or the Web of Science. The quality and scientific validity of articles published in the journal have been criticized by medical experts, and some of the viewpoints advocated by AAPS are rejected by mainstream scientists and other medical groups.[24] The U.S. National Library of Medicine declined repeated requests from AAPS to index the journal, citing unspecified concerns.[24]

As of September 2016, JPandS was listed on Beall’s list of potential or probable predatory open-access journals.[25] Quackwatch lists JPandS as an untrustworthy, non-recommended periodical.[26] An editorial in Chemical & Engineering News described the journal as a “purveyor of utter nonsense.”[27] Investigative journalist Brian Deer wrote that the journal is the “house magazine of a right-wing American fringe group [AAPS]” and “is barely credible as an independent forum.”[28] Writing in The Guardian , science columnist Ben Goldacre described the journal as the “in-house magazine of a rightwing US pressure group well known for polemics on homosexuality, abortion and vaccines.”[29]

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I really don’t see it being denouncedas dangerous, but rather its well known risks are pointed out. It does have risks, especially in people with cardiac involvement, which is a high number. That risk is amplified somewhat when combined with azithromycin. However, the risk is low enough that it has been widely used and studied, and the studies show no significant benefit. In that case, the even small risk seems to outweigh the benefit.

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I think part of the concern is that with COVID-treatment, it is often being used with a cocktail of other drugs and being introduced to bodies dealing with different stresses than healthy bodies looking for malaria protection or bodies with lupus or rheumatoid arthritis. So you can’t just assume the side effects will be the same. The effects of the combinations with other drugs in the context of the damage that COVID does to the body are not nearly as well studied, and multiple studies that have been done point to negative results or negligible benefits.

For example, one (not yet reviewed) paper found that while apparently safe alone, when combined with azithromycin, hydroxychloraquine could induce heart failure.

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Now I take that as a personal insult. There is just one set of facts. For example, has there been an RCT of hydroxychloroquine for early, high risk outpatient treatment of Covid-19?

And if that were done, then some would say that they failed to test it in right-handed people vs left-handed, or type A blood vs type B. You can goggle it, but here are a few studies that come up: https://www.nejm.org/doi/full/10.1056/NEJMoa2019014
https://www.nejm.org/doi/full/10.1056/NEJMoa2016638

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The first trial is of hospitalized patients, where the disease has already entered the second stage of pneumonia, where HCQ would be of limited help. The second study is of people who would be at low risk if they caught the disease. What is interesting is that a meta-analysis found that if HCQ is given within the first two days after exposure, it is very effective as a prophylaxis. But your comment reveals that either you did not bother to read Dr. Risch’s articles, or you missed the point. If the trial is testing low risk patients treated with HCQ against low risk patients not treated with HCQ, then it is unlikely to show much benefit, since neither group really needs treatment to begin with. Interestingly, the treated group did show minor benefit. But what we desperately want to know is whether early treatment of high risk outpatients yields significant benefit. And so far, there are no RCTs of that. But there is signficant retrospective evidence that it helps significantly. And that justifies using it and justifies the FDA approving an EUA for it.

It’s not me, it’s a bunch of other scientists. And yes, when you cite two bad studies and a google document, it’s not particularly impressive like his Newsweek article where he makes grand claims without good evidence. And like his colleagues at Yales and Dr. Fauci said, if we get better evidence they will update their perspective.

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Its regrettable that hcq like much of Covid 19 has become so politicized. Even now truly don’t know if hcq may have some benefit for early patients. All the studies have been flawed to a degree such as the uk study administering such high doses of hcq. It should be noted that Baric in his gain of function studies with the Wuhan group was making SARS virus chimera infective to human cells and found that zinc is inhibitory to the virus via the rna polymerase. Hcq is a zinc ionosphere and zinc seemed to have greater effect with hcq in some of the studies on covid 19. It seems that if hcq is effective it would be effective due to anti viral effects and not immune suppression and would be most beneficial in early stages of infection as you suggest but our docs have been prevented from using like they were with steroids.

It’s clear that due to the nature of this virus that it should be treated as early as possible especially in the high risk to mitigate severity and potential long haul effects.

Our medical system has not performed well during this crisis particularly with the dexamethasone disaster where our cdc and medical providers decided not to use steroids on patients based on a hypothetical letter in the lancet even though reports from China were showing benefit.

Still there are a number of promising potential therapies for early intervention that are arising and in use aggressively that we need to Id the high risk patients before they come in hospital and admin early to prevent onset of severe symptoms and long term damage. If someone thinks they have this virus they need to treat aggressively from the start.

It is worthwhile also restating as I and many others are stating that our population simply needs to supplement with vitamin D (C and k2 and zinc) It’s amazing that our health leaders have not taken this step while many other countries are making this recommendation. It is clear that about 40% of the population has T cell immunity to the virus which is likely due to their underlying immune health while a large percent of our population is Vit D deficient overweight (40%)and immune compromised particularly when it comes to this virus and all they are told is wear a mask. Unbelievable.

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For reference, here is one of the researchers from the papers you are referring to explaining how a lot of people misunderstand T-cells and how it doesn’t mean “immunity” to the virus:

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I would say that calling Dr. Risch dishonest constitutes an attack. As far as I can tell, neither you nor the Yale colleagues cite which studies you consider badly flawed nor why. Dr. Risch went to great lengths in his paper and attached letter to his critics to explain why he considered the five studies he cited to be worthy evidence. We are in a pandemic. The RCTs for early outpatient treatment are not expecterd to be done for some time to come. Meanwhile, thousands of people are dying daily. You take the evidence you have and make appropriate medical decisions based on that.

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Yes I do find it dishonest when he says this about the FDA:

I can only speculate about the cause of the FDA’s recalcitrance. Hydroxychloroquine is an inexpensive, generic medication. Unlike certain profit-generating, patented medications, which have been promiscuously touted on the slimmest of evidence, hydroxychloroquine has no natural financial constituency. No one will get rich from it. Further, it seems quite possible that the FDA, a third of whose funding comes from drug companies, is under intense pressure from those companies to be extremely conservative in its handling of hydroxychloroquine.

He just makes up speculation that the FDA is dishonest and drug companies are suppressing the truth about HCQ. Yes I call that dishonest to just claim that since nobody can make money off it (which definitely isn’t true - especially if you get people to buy the non-generic Plaquenil pill:

https://www.goodrx.com/hydroxychloroquine?dosage=200mg&form=tablet&label_override=Plaquenil&quantity=60

Also for reference, here is one of his Yale colleagues who does discuss one of the bad studies on HCQ that is often cited as evidence for it:

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My reply will be piecemeal. First, as far as I know, Dr. Risch has not used the 3737 Raoult study. Just the initial 26 patient and 1061 patient studies. In the 1061 study, all patients received treatment. So their results are compared to results of the population at large. They compare very favorably.

Correction: Dr. Vincent Fleury criticized Risch’s use of the 1061 study. Risch accepted the criticism and then referred to the 3737 study:

Seems the politicization has led to the inability of doctors to run prophylaxis and early treatment type trials.

As others have stated on this thread, I am also skeptical of the use of hydroxychloriquine to treat Covid. It’s unfortunate that the politicization has made it likely impossible to know for sure. What is needed is a prospective controlled trial. Retrospective analysis will not suffice

BTW: While at Johns Hopkins School of Medicine, I trained with and have a paper coauthored with the doctor, Dr Jon Giles, who is now at Columbia U and was interviewed for that NPR story. So I know he’s a reputable physician with high academic standards

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