More evidence hydroxychloroquine works

If you need to believe that gynecological problems come from sex with demons and witches, that alien DNA is used in some medical treatments, that vaccines can prevent people from being religious, that reptilians and other aliens have infiltrated the US government, that hydroxychloroquine works on COVID-19 patients, and that face masks are useless against COVID-19, I'm sure that you can find someone who will assure you that those things are true.

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Eureka! Sand is the cure!

 

Are you in the wrong thread? lol

 

The thread's title clearly identifies it as a colloquium concerning a crackpot notion.

 

Oh wow, don't get me started on Dr. Didier Raoult. I know him very well including having listened to one of his lectures (I speak fluent French). I read in their entirety his studies in original source, AND the strong criticism they received on basis of methodology. Talk about the pot calling the kettle black, and someone in a glass house throwing stones. Professor Raoult's original study had the SAME peccadillo he is now pointing fingers at, given that he excluded from his study three patients who had bad outcomes in the HCQ group, prompting critics to say "it's easy to show good results in a small study of 25 patients separated in 2 groups when you take out of your treatment group the ones who did really poorly."

Also, his second study was borderline fraudulent in having compared his treated population of outpatients (which much milder illness) with a population of hospitalized patients (by definition with much more severe illness) to tout the better outcome he achieved with his patients - basically comparing apples and oranges. Dr. Didier Raoult plain refuses to do randomized controlled trials, arguing that they are unethical by denying to the placebo group, the benefits of treatment (which is not a valid objection given that the control group still gets treatment as usual, just, doesn't add to treatment as usual, the investigational medication).

This said, I don't doubt that the study he criticized may indeed be subject to criticism, that is, he may very well have a point and when that study is submitted to peer review it may be rejected given the shortcomings he underlined. This is not to say that HIS studies don't have similar shortcomings... And to make it worse, it's been shown that the peer reviewers who reviewed his two studies were not blind as to who authored them, and had ties to him. The peer review of his two studies has been called hasty and biased, in not spotting the two obvious shortcomings in methodology I've mentioned above, which were apparent to me since I read the two studies, much before I read the criticism.

 

Agreed. This is indeed despicable and criminal.

This said, I definitely don't believe that all studies are tainted like that. Some are, some aren't. I like to think that the ones that aren't, predominate. There are still many idealistic and ethical people who just want to do a decent job and make a contribution to public health and the medical sciences. I've personally met and attended presentations from numerous researchers who print "nothing to disclose" on the mandatory disclosure slide, and say to the attendees "I definitely make less money than those who have a long list of disclosures, but I prefer to keep it this way because I'm in the business of making unbiased and ethical science."

I like to think that most human beings are decent people. It doesn't mean that the greedy ones even if in the minority, aren't very powerful and don't have a disproportionate share of influence. But there are still many in the scientific community who resist the push and just want to do a good job. Lots of scientists went into science, typically not the most lucrative field (except for the ones who get to patent innovations and accept to be corrupted by big business) for idealistic reasons.

Think of an MD/PhD medical scientist. Who do you think makes more money? The ones who go into the MD side of large private practices, or the ones who go into the PhD side of a salaried position in some academic lab? The former, obviously, so the latter typically don't go into this for profits, but rather for idealistic attempts to make a contribution to humankind in the advancement of medical sciences.

 

Why are there crackpots who are still hopelessly deluded concerning hydroxychloroquine?

 

So HCD is over-the-counter in Iran, can't be very dangerous after 65 years of use.

 

Not fake science, just doctors who do not agree. Let the experts continue arguing and testing theories and eventually the scientific method will force a conclusion.

 

As far as hydroxychloroquine is concerned, it's been done already. The conclusion is that it doesn't work to treat or prevent the disease. This conclusion is final, uncontroversial, definitive, abundantly demonstrated by a mountain of data, and those who state the contrary are frankly deluded. Unfortunately there are still many deluded folks out there including many doctors who still swear by it, and many observational studies, most of them hopelessly flawed (including the original one by Professor Didier Raoult), that wrongly try to support it (against the much higher level of evidence provided by randomized controlled trials).

The failed hydroxychloroquine saga is one of the biggest fiascos in the history of modern medicine, and the only reason why it happened is that politics got in the middle of it. For any other drug known to men in the medical field, small pilot studies followed by observational studies that suggest *possible* efficacy are then put to the real test of randomized clinical trials, and when these conclude and confirm that the initial optimism was unwarranted and the drug doesn't work (which is the case historically for nine out of ten such attempts), everybody accepts the superiority of the RCTs to provide definitive judgment, accepts that it is true that it doesn't work, and everybody moves on to try other things.

It's ONLY because politicians such as the Minister of Health of France, president Jair Bolsonaro of Brazil, president Donald Trump of the United States, and others, got all enthusiastic about it, that people who have NO CLUE about what constitutes efficient proof of efficacy or lack thereof, became pundits on it, organized huge media coverage of it, and drew in lots of passionate supporters who got into this collective delusion that there is some sort of vast scientific conspiracy to discredit the drug for political purposes, ignoring for example that great studies that showed no efficacy were done in countries that were NOT part of this political push, such as the United Kingdom and its authoritative RECOVERY trial done by Oxford University and the National Health Service. I mean, if anything, the UK government is also right wing and aligned with Trump, and they'd be delighted with Trump's re-election; why would they have an interest in discrediting a drug that Trump has touted??? Still, this study, a true RCT with 11,000 patients and methodologically flawless, concluded in the strongest possible terms that the drug doesn't work.

The conclusion that it doesn't work is NOT political, folks. It is medical.

On the other hand, a drug that Trump has ALSO touted, remdesivir, did get positive results and is now routinely accepted in the best COVID-19 protocols. I guess if the medical community wanted to just stick it to Donald Trump, we'd have destroyed the reputation of remdesivir too, right? That nobody did that, goes to show how absurd the idea that when studies show that HCQ doesn't work, it's just to stick it to Donald Trump.

And no, it's not fake science. Yes, there were two fake studies published. They were spotted in their inconsistencies and immediately retracted. That doesn't mean that the others are fake, too. Like I said elsewhere, the fact that someone robs a bank in South Dakota doesn't make of a Florida resident who has never been to South Dakota, also a bank robber. The fact that the rogue group Surgisphere sponsored a fake study and managed to get it in The Lancet (briefly, then the ruse was discovered and the study was retracted), doesn't mean that extremely prestigious Oxford University also ran a fake study. The Oxford one is definitely not fake, and it ALSO shows that HCQ doesn't work. Period, full stop.

 

Serous research into promising drugs cannot be impaired by celebrities touting one to which they have taken a fancy after it has been eliminated as being an efficacious one.

 

IMO, Dr. Raoult and everyone else who defends the use of HCQ or any other cheap effective treatment will be dismissed as an unreliable at least until 11/20.

“A total of 539 COVID-19 hospitalised patients were included in our cohort in Milan, from February 24 to May 17,2020 of whom 174 died in hospital (day 14 probability of death: 29.5%–95%CI: 25.5–34.0). We divided a subset of our cohort in three groups who started treatment a median of 1 day after admission: those receiving hydroxycholoroquine alone (N = 197), those receiving hydroxycholoroquine + azithromycin (N = 94), and those receiving neither (controls) (N = 92). Of the latter group, 10 started HIV antivirals (boosted-lopinavir or –darunavir), 1 teicoplanin, 12 immunomodulatory drugs or corticosteroids, 23 heparin and 46 remained untreated. The percent of death in the 3 groups was 27%, 23% and 51%. Mechanical ventilation was used in 4.3% of hydoxychloroquine, 14.2% of hydroxycholoroquine + azithromycin and 26.1% of controls. Unweighted and weighted relative hazards of mortality are shown in Table 1. After adjusting for a number of key confounders (see table), the use of hydroxycholoroquine + azithromycin was associated with a 66% reduction in risk of death as compared to controls; the analysis also suggested a larger effectiveness of hydroxychloroquine in patients with less severe COVID-19 disease (PO2/FiO2 > 300, interaction p-value<.0001). Our results are remarkably similar to those shown by Arshad et al.”

International Journal of Infectious Disease, Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and dusted situation?, Antonellad’Arminio MonforteAlessandroTavelliFrancescaBaiGiuliaMarchettiAlessandroCozzi-Lepri
https://doi.org/10.1016/j.ijid.2020.07.056
https://www.sciencedirect.com/science/article/pii/S1201971220306007
https://www.ijidonline.com/article/S1201-9712(20)30600-7/fulltext

 

The replication crisis, Fake Science, is a very serious problem.

"Can’t take criticism? Just make up your own reviews! It may sound far-fetched, but we’ve now counted more than 270 retractions, more than half of them this year, which occurred because authors or editors compromised the peer-review process in some way—most egregiously, some authors faked email addresses for peer reviewers and gave their own papers a green light."
THE SCIENTIST, The Top 10 Retractions of 2015, A look at this year’s most memorable retractions, By Retraction Watch | December 23, 2015.
https://www.the-scientist.com/?articles.view/articleNo/44895/title/The-Top-10-Retractions-of-2015/

 

It's actually Fake Science. Both Lancet and the NEJM have been caught red handed.

 

Thanks for the link. It's interesting and I bet these people mean well. No conflict of interest, no funding. But please do understand that this is *still* another retrospective observation of a cohort without randomization. This is not a randomized controlled trial. We've had observational studies a dime a dozen, and some seem to favor HCQ, while some seem to favor other treatments or suggest that HCQ is detrimental. Please don't engage in selective quoting of only those observational studies that seem to support HCQ, because there are plenty that do not. So what do we do when it's like this? We run RCTs to sort it out. And invariably... the RCTs have been showing no efficacy.

Look, these people know about it. Here is what they say:

Yep, you got it. Unmeasured confounding. That's EXACTLY the problem with retrospective cohort observations, against the purity of RCTs.

We have for a while moved our practices to what is called Evidence-Based Medicine. So, we look nowadays at the "strength of evidence" to decide what treatments are evidence-based, that is, it's pretty proven that they work, versus others that are tentative and speculative. So, in order to guide our views on this, we've established six categories of strength of evidence, 1 through 7, 1 being the most authoritative and most convincing, and 7 being the weakest and least relevant.

Large randomized clinical trials are universally ranked as Category 1.
Observational retrospective cohort studies like this one, are ranked as Category 6 (the second weakest, only behind untested expert opinion)

So, one could say, how does Dr. Antonella D'Arminio Monforte and her four Italian colleagues dare to contradict, with their retrospective non-randomized observational analysis of 539 patients, the RECOVERY randomized controlled trial with 11,000 patients and perfect methodology???

I'm frankly getting sick and tired of these people who write letters to the editors touting their "findings" which are invariably nothing better than retrospective observations of cohorts, with a zillion confounding intervening factors, to question the MUCH BETTER RUN, MUCH STRONGER METHODOLOGICALLY, MUCH MORE STATISTICALLY POWERFUL randomized controlled trials. If Dr. Antonella D'Arminio Monforte and her colleagues are so adamant about it, they are welcome to run an RCT. Well, you know, that's not so easy. Any Dr. Mary Doe and four assistants can look at a bunch of charts and do an observational study. Running an RCT is A LOT more difficult and more involved, so, Dr. Monforte, please, give the RCTs some respect, will you?

The inevitable demand at the end in these letters to the Editor, are just what she said: "we question whether hydroxychloroquine should be further tested."

Sorry, Dr. Monforte, but you're late to the game. This ship has sailed. It HAS been further tested already. By some very good people, probably with a lot more expertise than you have, namely, the Professors of Medicine at the #1 ranked university in the world, Oxford University (the same folks who are about to deliver the mRNA vaccine that may simply save humankind from this scourge).

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Now, about this phrase of yours:

"IMO, Dr. Raoult and everyone else who defends the use of HCQ or any other cheap effective treatment will be dismissed as an unreliable at least until 11/20."

Now, you're making a lot of assumptions here, at least as far as I'm concerned.

When Dr. Raoult first had the idea and published his small non-randomized pilot study, NO POLITICIANS HAD TOUTED THIS THING YET!!!! I read it shortly after it was published, in original French. While I was hopeful (we were in the early days of the pandemic and anything that might be helpful was welcome) I was *already* uncomfortable with the methodological flaws. So, in France (a country I know VERY well), there is always some tension between the provinces and the capital city, Paris, a lot of jealousy. So, shortly after Dr. Raoult published his findings, a group in Paris tried to replicate them. They used the exact same protocol he had used, the exact same doses of HCQ and AZ, measured the same outcomes, and came up empty. They could not reproduce his findings. They published, countering what he had found. Well, that pissed off the good professor Raoult. He then published his second study, in my opinion MUCH WORSE in methodological terms, responding to the Parisian group. Again, this was before the politicians woke up to it. I read the second study too, and thought, "oh my, this is not good, he's comparing outpatients to inpatients!!!" Then I listened to a lecture by him. I was utterly unconvinced and found him a bit nutty, frankly, especially when he said he is against randomized controlled trials and will never run one.

Again, this was all before this whole thing exploded. And the criticism against both his papers was also issued before the politicians got in the middle of this. Up to that point it was just academics as usual, and the usual back-and-forth between research groups and reviewers.

Now, it might be interesting for you to realize, if you haven't heard this yet, that after the methodological criticism was issued against his two studies, the very organization that accepted them for publication did an about-face and declared that the studies were not "up to our standards." They didn't retract them... but that's pretty damaging, you know?

So, with your 11/20 mention, would you be insinuating that my position on this is being influenced by the American upcoming general elections? I can assure you that it isn't.

Also, you might want to consider that the money side of this is not as clear cut as you think. I mean, I bet the small start-up Gilead Sciences would rather see their expensive medication remdesivir prevail over cheap HCQ, but see, Gilead Sciences is not even Big Pharma and I doubt their reach is such that they'd be able to sabotage HCQ. Now, think of this: HCQ was sold for $5 all over Africa for a supply to treat/prevent malaria. Do you know how much it costs, now, after the hype? $95. That's a 19-fold jump. And it's generic so ANY PHARMA COMPANY can make it and sell it for 19 times its original price in this vast and populous continent and in places where it remains popular like Brazil, an also vast and populous country.

Don't assume that Pharma can't profit from HCQ. Far from it. There may be more moneyed interests vying for preserving the "HCQ for COVID-19 myth" against all the evidence delivered by reputable RCTs, than the opposite, moneyed interests discrediting it (which for now would only benefit the small Gilead start-up - I don't even thing they have enough clout to influence anything).

Pray tell, what exactly are those other players who would financially benefit from discrediting HCQ? The ONLY two medications that have achieved unequivocal positive results in RCTs for COVID-19, as of now, are remdesivir (which is owned by ONE small company; it's under patent; no others will benefit from it) and dexamethasone, which is just as generic and just as cheap as HCQ.

None of the big players (Pfizer, Johnson & Johnson, Eli Lilly, GlaxoSmithKline, etc) have any medication in the pipelines that is looking promising to treat COVID-19, so what exactly is their interest in destroying HCQ's reputation??? I frankly fail to see it.

Other than remdesivir, everything else that is being studied is repurposed, most out of patent already. There are 21 medications used for a varied of things, being studied to see if they have any action against the SARS-CoV-2. I know of none that is a very expensive, under-patent medication owned by a large Big Pharma company that is under serious consideration and might drive a financial interest in discrediting HCQ.

Again, HCQ is being discredited simply because... it doesn't work. No conspiracy theory necessary. Sometimes things are a lot simpler than they seem.

 

I THINK THAT MAKES IT RACIST IN 2020: Study: Antiviral drug remdesivir helps white, Black and Latino patients equally.

 

OK, I know that, but do you have any idea how many papers are written every year??? Take a wild guess. I bet you won't get even close to the total.

All right, let me tell you: 2 million. There are about 30,000 scientific journals and they publish about 2 million papers per year.

https://www.universityworldnews.com... each year.&text=Our argument is a simple one.

So, say, "270 retractions, more than half of them this year" - So half of 270 is 135. More than half? Let's make it 150.

OK, so, 150 out of 2 million, the retracted papers are 0.0075 per cent of the total.

See why I say that the majority of scientists are NOT the unethical ones who get involved in fraud?

0.0075% is pretty inside the bad apples that you see everywhere in every profession and every sector of human activity, right? It's probably, actually, a smaller proportion of bad apples than in other sectors. Would you say that only 0.0075% of all car dealers are less than honest? Only 0.0075% of all lenders? Are only 0.0075% of all employees lazy and prone to cutting corners and fooling the employers? Only 0.0075% of all lobbyists? Do you think that only 0.0075% of all lawyers are less than trustworthy?

And get this, only 0.0075% of all politicians?

You might say "but that's just the ones who got caught; it's probably more." Maybe but not by much, because how do you suppose these got caught? Because others looked at their papers after they were published and found flaws and inconsistencies. The scientific community is notoriously good at doing this. Just look at the Lancet and NEMJ fraudulent papers: they got caught and retracted pretty darn fast, thanks to how vigilant the scientific community is. So, no, it isn't that likely that many more than these 150 are fraudulent.

 

LOL, interesting.

 

Everything the right does not want to hear is "fake news." Everything the right does not want to accept as science is "fake science." It is all so exhausting.

 

I’m happy to see you address the fact none of the trials so far actually involve the regimen claimed to be effective from the beginning. I don’t believe this is an accident. To say it’s an accident is to say the scientific/medical community is inept. I beat this horse early on here at PF, showing the research in vitro that led to doctors trying HCQ+zinc in the first place. When in vitro evidence moves to trials in vivo you don’t drop a key component of the in vitro research. To do so is either stupidity or disingenuous.

With that, I’m out on this issue. I’ve made my views known and stand by them. But it’s nice to see someone else point out the (what should be) obvious flaw to the current narrative.

 

In vitro and in vivo are VASTLY different, in medicine, especially when the in vitro concentrations are unlikely to be achieved by in vivo doses. The history of medicine is full to the brink of promising in vitro effects failing miserably when tested in vivo in humans, with non-toxic doses being unable to reproduce the in vitro effect. It's a lot more the rule than the exception that in vitro effects can't be reproduced in vivo, which has been the case so far for HCQ and the SARS-CoV-2.

Studies have extensively tested HCQ + AZ, and some indeed have tested HCQ + AZ + Zinc. The one niche that is missing is seeing if Zinc alone is responsible for any efficacy, if any. Like I said, while I acknowledge that this niche has been the least explored, I'm not highly hopeful for it, given that the human body does already possess Zinc, so the, by now, EXTENSIVELY demonstrated inefficacy of HCQ against the SARS-CoV-2 might not be that much enhanced by adding Zinc.

To call the scientific community that with 7 months of a new disease has already delivered the full genome of the virus, several methods of making a vaccine (mRNA, inactivated virus, attenuated virus, adenovirus vector, protein fragment) that are already having ongoing Phase 3 trials or getting close to them in absolutely record time - at least 4 times faster than the previous record - has found two medications that showed unequivocal benefit in randomized clinical trials - remdesivir and dexamethasone - and that perfected the critical care protocol - which now includes early anticoagulation, early steroids, and other anti-inflammatory drugs to dampen the cytokine storm, and new ways to deal with ventilator candidates - to the point that ICU recovery rates went up the roof contributing to a drop in death toll, not to forget the heroes that have constantly battled this horrible and dangerous disease with front-line exposure with PPE shortage that has resulted in doctors and nurses catching the virus and some dying - INEPT of all words, frankly seems terribly offensive to me.

I wonder what non-inept contribution you've made to this effort, to be able to cast a huge classe of people doing their best to control the contagion and treat the affected, under such a pejorative word.

Please, kindly disclose your personal contributions to this effort. Are you personally spending days and nights and weekends in labs trying to find solutions? Are you personally running randomized clinical trials with all the complexity and hardship that they entail, from funding to running to analyzing to publishing? Are you personally going to the front lines and exposing yourself to the virus in a compassionate attempt to heal the sick? I won't exclude that you are, and in this case I'll accept your criticism. But if you aren't, I would humbly suggest that you show a modicum of respect to the heroes who are doing all these things.

Cheers.

 

No, he is just a true believer in the Fauci created narrative.

 

Not just exhausting, it is flat out dangerous. Next, the anti-science crowd will advocate against a vaccine, if it should come out. Because the deep state....

If this anti-science movement continues after Trump is out, I am afraid for the future of this country. What these news and science deniers are doing is actually actively undermining every institution that have made this country great, by planting distrust: The government, universities, schools, medical institutions, courts (activist judges..), the FBI etc. When everyone loses trust in all of those institutions, there can be no country.

 

Grand juries should have started asking questions about deadly dosage decisions from the start.

 

In fact, Lancet and NEJM were caught, literally red handed, publishing deadly Fake Science.

"NEW YORK/LONDON (Reuters) - An influential study that found hydroxychloroquine increased the risk of death in COVID-19 patients has been withdrawn a week after it led to major trials being halted, adding to confusion about a malaria drug championed by U.S. President Donald Trump."
U.S. NEWS & WORLD REPORT, 'Truly Sorry': Scientists Pull Panned Lancet Study of Trump-Touted Drug, By Reuters, Wire Service Content June 4, 2020.
https://www.usnews.com/news/top-new...influential-lancet-hydroxychloroquine-article

"Truly Sorry". Do you accept their apology?