Holy smokes it's like trying to play whack-a-mole. Too many truly world-class morons to award Moron Awards to everybody and we're running out of Moron Spray. But these guys deserve an honorable mention for idiocy, stupidity, and just being outstanding dumbasses!
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Coronavirus
- Thread starter Wenche
- Start date
Holy smokes it's like trying to play whack-a-mole. Too many truly world-class morons to award Moron Awards to everybody and we're running out of Moron Spray. But these guys deserve an honorable mention for idiocy, stupidity, and just being outstanding dumbasses!
bkp_duke
Well-Known Member
OK, you obviously don't have scientific training, so let me dumb this down so that you can understand it.
1) The sample size in the "44%" study you keep referring to is too small to be able to make that kind of statistical claim. THINK ABOUT IT. If the fatality rate of COVID-19 is somewhere around 1% (+/- 0.5%). The sample sizes your study refers to were ALL LESS then 100-150 (and IIRC many were around 50). A simple power calculation would show that you need THOUSANDS of samples to tease out a 5% improvement in results.
SO STOP SAYING A 44% IMPROVEMENT - THAT'S AT BEST A GROSS MIS-REPRESENTATION OF THE STUDY, AND AT WORST A FLAT OUT LIE.
2) Sample Bias - this one is HUGE. By design, retrospective studies are biased because the researchers pick and chose what data points to include and exclude. The researchers are NOT blinded at all, and if someone, say, DIED, they can exclude that from their reporting with no consequences. THIS IS THE PRIMARY REASON STATISTICS ARE NOT TO BE REPORTED WITH RETROSPECTIVE STUDIES. THEY GROSSLY OVER-ESTIMATE AN EFFECT DUE TO SAMPLE INCLUSION/EXCLUSION BIAS. This is EXACTLY why all of the ORIGINAL HCQ studies showed LARGE effects (the French study, the Chinese study) with or without AZTH or Zinc, but when PROPER studies were done that blinded the researchers to remove selection bias, those effect DISAPPEARED.
DO YOU UNDERSTAND THIS? IS THIS CLEAR? This is NOT be understated. It is EXACTLY why when researchers are publishing retrospective studies they are not to make statistical claims. LITERALLY - THIS SHOULD HAVE BEEN CAUGHT AT PEER REVIEW.
3) Original trials (France, China) did NOT include Zinc, and yet they showed MASSIVE improvements. Why? See point 2 above. The FDA approval was based upon those FLAWED studies, and when better studies came out and showed there was not an effect that could be measured AND there was significant harm, the approval was rescinded.
4) Your desired study is IN PROGRESS. The WHO is still doing it, and has been for the past 4 months (with a one month break when the detrimental data for HCQ came out). IT DOES INCLUDE ZINC ON ONE TREATMENT ARM.
WHO resumes hydroxychloroquine study for Covid-19
Those researchers have already given us a preview of their findings:
"The same group of researchers is also planning to publish the results of trials testing the drug as a treatment and as a “pre-exposure prophylaxis” — that is, before any exposure to SARS-CoV-2, the virus that causes Covid-19.
The latest trial enrolled 821 patients who were either living in the same household as someone with Covid-19 or who were health care workers who had been exposed to someone with Covid-19 without adequate protective gear. While the initial infections had to be confirmed with a diagnostic test, the researchers also counted patients who had symptoms consistent with disease, in part because testing wasn’t available.
Approximately 12% of those given hydroxychloroquine developed Covid-19, compared to 14% who were given the vitamin folate as a placebo. There was no further benefit among patients who chose to take zinc or vitamin C."
You need to understand that while this is an on-going trial - THAT IS NOT THE RESULT you want, and STRONGLY argues agaisnt your 44% number. In fact, if 44% decrease in infection were in FACT the case, we would have rock solid data from the enrolled patients already to support that.
bkp_duke
Well-Known Member
You CANNOT even make that 2% claim. And it really shows that you don't understand statistics, at ALL.
Most likely, the 12% and 14% numbers have margins of error that cause them to overlap so much, that a P-value calculation between the two groups show NO STATISTICAL SIGNIFICANCE.
I.e. if there is a margin of error of 3% in the 12% and 14% groups, that means they overlap enough to have a P value way above significance.
That's a really good catch and a useful resource in terms of summarizing all the claims about hydroxychloroquine and who's making all the claims. One of the sobering facts for people who still want to believe in hydroxychloroquine is that the current groups pushing this are like a Who's Who Rogues Gallery of Idiots. Stella Immanuel who is fully psychotic, the Bakersfield ER docs who have been professionally censured, Breitbart News, etc etc. No well-respected person other than the Yale epidemiologist is saying anything positive about HCQ. And the Yale Medical School faculty Dean recently distanced himself from this guy saying that he does not want to get into this set of issues but he allows his faculty to be as he puts it "contrarian," and he is the only person that I'm aware of with a decent resume currently supporting hydroxychloroquine use, who has not already been discredited, censured, exposed as a quack, exposed as somebody making claims without data, etc etc. That's a rather small fraction. One potentially competent person and then the Rogues Gallery of Looney Tunes Characters and Idiots. That's your support base for hydroxychloroquine at this point.
So, not to put too fine a point on it, but who do you want to believe at this point? Anthony Fauci or Daffy Duck?
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bkp_duke
Well-Known Member
I think you guys have hashed this one out about as much as it can be hashed.
Here's the problem with retrospective studies - as you know they can never separate correlation from causation. Some of the retrospective studies have showed what looks like an impressive benefits but you can't really draw any conclusions from those. All you can do is say maybe there's enough signal there that a properly randomized and controlled study would be able to find it. It's pretty clear at this point that hydroxychloroquine by itself does not have any such signal. Possibly combined with zinc there might be some signal but again hydroxychloroquine is a crappy way to get zinc into cells. If that's really the therapeutic effect of the combination we have far less toxic zinc ionophores, although I doubt they will be studied because they're cheap nutritional supplements. It's also doubtful that once patients become severely ill that therapy targeting an increase of intracellular zinc is going to be helpful. At that point clotting and / or severe inflammation and sepsis are killing people. If there is a role for zinc it looks like it's early before any version of cytokine release syndrome, severe pneumonia, devastation of endothelial cell lines with release of Von Willebrand factor Etc
One of the challenges, has Anthony Fauci himself has pointed out, is this is an enormously heterogeneous and variable disease. A significant fraction of folks have cross-reactivity of T Cell populations based on exposure to prior coronavirus now confirmed as related to S protein epitopes, and are either asymptomatic or minimally symptomatic. Another significant fraction perhaps head into a much more severe illness, with severe pneumonia and sepsis but as we've learned that's not the only lethal trajectory as another group develop severe pathological clotting and this may contribute to both lung failure, strokes and heart attacks. Finally kidney failure is another lethal trajectory.
We don't have the ability at this point when people become severely ill to know which one of those trajectories they're going to get into, as I'm not aware of any clear biomarkers that have predictive value. We are seeing the emergence of more differentiated therapy approaches such as use of anticoagulants early but at this point we still don't have clear biomarker prediction pathways.
Future therapies will no doubt be much more differentially and specifically targeted to those biomarker heuristics. I know a lot of your posting is aimed at trying to get a positive message out, but there is progress, we do have Remdesivir which may moderate severity, and for patients that had into nasty pneumonia / sepsis pathways, dexamethasone looks to be disease-modifying, and there is for sure increasing appreciation and clinical intervention around pathological clotting. I know the progress in getting close to or at least approaching the asymptote of effective and definitive treatment protocols is painfully slow. But what else is new. There is just so much humbling complexity to appreciate and map out.
It's not just the correlation from causation issue with retrospective studies, it's the selection bias, and in the case of the study papafox is so fond of, the sample size.
It's like trying to extrapolate the entire composition of the pacific ocean by doing a chemical analysis on one drop of water. . .
SageBrush
REJECT Fascism
JRP3
Hyperactive Member
The "bias" is in line with the actual science, which you want to ignore, for some reason, which might be described as a "bias".
Listen to Fauci if you haven't yet done so, he lays it out quite clearly:
Ford study was flawed, RCTs don't show it to be effective, and if an RCT did show it to be effective he would recommend it as treatment. That's a rational, scientific approach.
We've literally been saying we need RCTs to settle this debate, you'd have to be actively skipping some of our posts to miss that.
N5329K
Active Member
I think it’s fair to say that all HCQ studies to date have been somewhat flawed and don’t incorporate the full Monty treatment with zinc, but they have all, despite their flaws, indicated no therapeutic benefit. They are points that define a trend, and, when compared to the known side effects, the trend is decidedly negative. Doesn’t mean there MIGHT not be the right time, place, patient and drug cocktail that shows a statistically significant benefit, but that trial has not been conducted and should probably take a way back seat to more promising therapies.
Seem fair?
Robin
SageBrush
REJECT Fascism
I've read enough of ppx's nonsense in the past to be able to answer this: as the family member of a physician, he thinks he knows best how to structure the penultimate RCT; and since none have been done to his latest satisfaction, he discounts the RCTs to date.
His stance is equal parts pathetic and funny. The only rational response is to ignore him.
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@dfwatt, I don't really pay much attention to epidemiologists who try to play MD on twitter, Yale association or not. I wonder though, is this the same fool who was telling Twitter that donated plasma was available for all because donors could be bled twice weekly indefinitely ?
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SageBrush
REJECT Fascism
Unlikely, given the negative RCTs to date. It might lead to a recc for further study if the RCT was overwhelmingly positive, very high powered, and a reasonable argument made why the results differ from the other studies. Otherwise it would just be one outlier and meta-analysis would not support a change in treatment approach.
Apropos of the professional integrity/quality (or lack thereof) of people supporting hydroxychloroquine as a cure or even just as a treatment for Covid 19, here is a Medpage review of the phony Frontline Doctors viral video. Most of them aren't qualified to treat the flu. At least two of them should have their license pulled for what they've been saying particularly Immanuel who frankly looks like a woman who needs a psychiatrist badly, and one of the Bakersfield docs who was professionally censored. I wouldn't send my dog to any of these idiots. They're certainly not on the front lines in any sense in relationship to Covid 19. This is essentially disinformation promulgated by the Tea Party and other Libertarian far-right points of view, disguised as responsible medical opinion. It is to clinical practice advice what the completely discredited Santa Clara antibody study is to the calculation of IFR. Total horseshit.
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I think you guys have hashed this one out about as much as it can be hashed.
Here's the problem with retrospective studies - as you know they can never separate correlation from causation. Some of the retrospective studies have showed what looks like an impressive benefits but you can't really draw any conclusions from those. All you can do is say maybe there's enough signal there that a properly randomized and controlled study would be able to find it. It's pretty clear at this point that hydroxychloroquine by itself does not have any such signal. Possibly combined with zinc there might be some signal but again hydroxychloroquine is a crappy way to get zinc into cells. If that's really the therapeutic effect of the combination we have far less toxic zinc ionophores, although I doubt they will be studied because they're cheap nutritional supplements. It's also doubtful that once patients become severely ill that therapy targeting an increase of intracellular zinc is going to be helpful. At that point clotting and / or severe inflammation and sepsis are killing people. If there is a role for zinc it looks like it's early before any version of cytokine release syndrome, severe pneumonia, devastation of endothelial cell lines with release of Von Willebrand factor Etc
One of the challenges, has Anthony Fauci himself has pointed out, is this is an enormously heterogeneous and variable disease. A significant fraction of folks have cross-reactivity of T Cell populations based on exposure to prior coronavirus now confirmed as related to S protein epitopes, and are either asymptomatic or minimally symptomatic. Another significant fraction perhaps head into a much more severe illness, with severe pneumonia and sepsis but as we've learned that's not the only lethal trajectory as another group develop severe pathological clotting and this may contribute to both lung failure, strokes and heart attacks. Finally kidney failure is another lethal trajectory.
We don't have the ability at this point when people become severely ill to know which one of those trajectories they're going to get into, as I'm not aware of any clear biomarkers that have predictive value. We are seeing the emergence of more differentiated therapy approaches such as use of anticoagulants early but at this point we still don't have clear biomarker prediction pathways.
Future therapies will no doubt be much more differentially and specifically targeted to those biomarker heuristics. I know a lot of your posting is aimed at trying to get a positive message out, but there is progress, we do have Remdesivir which may moderate severity, and for patients that had into nasty pneumonia / sepsis pathways, dexamethasone looks to be disease-modifying, and there is for sure increasing appreciation and clinical intervention around pathological clotting. I know the progress in getting close to or at least approaching the asymptote of effective and definitive treatment protocols is painfully slow. But what else is new. There is just so much humbling complexity to appreciate and map out.
Thank you for posting an honest and useful response to this discussion. The limits of a retrospective study are real, as you suggest, but the results of this HCQ + zinc retrospective study are impressive enough to suggest a follow-up clinical trial. Let's hope that trial gets done. It's too early to either kill this treatment idea altogether or to label it as a roaring success.
bkp_duke
Well-Known Member
Do you not read?
The study is ALREADY ongoing. HAS BEEN ongoing for 3-4 months (with a 1 month pause).
I have no horse in the hydroxychloroquine debate so to speak. But I don't understand your affection for it in terms of why you feel there is still a sizable amount of room so to speak for it to be still potentially proven effective when there are so many RCT studies that have come back showing no impact or possibly even harm. I would say the "room for it to move" on this point is already pretty constricted. If there is any efficacy again it's as a zinc ionophore and again there are many less toxic alternatives. And the problem at this point is that any randomized controlled trial study showing efficacy would have to be replicated because right now that study would be regarded as an outlier. So I don't think you're fairly representing the weight of scientific opinion and evidence at this point when you say it's too early to say whether or not hcq would be regarded as a failure or a roaring success. There is simply no room in which it could be regarded as a roaring success. That possibility has been closed out. So I have to confess, I don't understand why you believe that there's still some great margin of high possibility that this drug is going to be proven effective. I think the margins on that are just about shaved down to almost nothing.
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Your responses to my posts have on several occasions been incorrect or implying something that doesn't exist, and I think you've known they've been incorrect, but you posted them anyway with the aim of winning your argument. What matters most is not one of us winning or losing an argument but rather that the topic gets discussed intelligently so that visitors to this thread have two sides of the story to consider. This thread deserves better discussions and your attempt to shut down the HCQ and zinc discussion once and for all is definitely premature. Let's look at some of your incorrect assertions:
* "Dexamethasone can easily be given as an outpatient (I agree with you on remdesivir), so that kills your outpatient argument for HCQ being the only thing that can be done."
Although dexamethasone can be given in an outpatient setting, unlike the HCQ + zinc therapy, it has little value given in such a setting. According to this article, although dexamethasone shows value for patients on ventilators and on oxygen, "There was no benefit among those patients who did not require respiratory support." In other words, Dexamethasone has a very specific benefit for patients who have progressed in the disease and are on ventilators or oxygen, but there is NO benefit to other patients. What bothers me is that your post implies there's a benefit to giving dexamethasone in an outpatient setting, which is entirely incorrect.
* "HCQ is SO BAD in terms of the side effect profile, no one is going to try it in a cocktail for COVID-19 when we have things we know improve morbidity and mortality."
The side effect profiles were gathered during the incorrect use of the drug. In some cases, too high a dose was administered. In others, the majority of patients were considered in a hospital setting, many with the disease significantly progressed, which is not the time to begin the treatment. It is likely that a negative effect could be happening to the patients when HCQ is given late in the process, once the battle in the lungs has already begun, that is completely unrelated to heart arrhythmia. The bottom line is that the side effect profiles you refer to are side effects when the drug was given at an inappropriate time. When used early and in conjunction with zinc, the side effect profile will likely be quite a bit less severe.
* "Approximately 12% of those given hydroxychloroquine developed Covid-19, compared to 14% who were given the vitamin folate as a placebo. There was no further benefit among patients who chose to take zinc or vitamin C."
The study was talking about using HCQ as a prophylactic, not as a treatment. The statement you quote is inappropriate for judging treatment effectiveness.
* "The researchers are NOT blinded at all, and if someone, say, DIED, they can exclude that from their reporting with no consequences."
Seriously, how can you type that sentence with a straight face? One member of the HCQ + zinc group did die, and they reported it. No consequences? Are you suggesting nobody in the study had any scruples? Not one person?
* "THIS IS THE PRIMARY REASON STATISTICS ARE NOT TO BE REPORTED WITH RETROSPECTIVE STUDIES. THEY GROSSLY OVER-ESTIMATE AN EFFECT DUE TO SAMPLE INCLUSION/EXCLUSION BIAS."
OK, let's look at the sample group. Zelenko only gave the cocktail to patients over 65, those with a preexisting condition, patients with a shortness of breath, or a patient who looked particularly bad. This is not cherry-picking the sample group. If anything, the sample group was at greater risk than the control group.
Take a look at some of these statistics.
4 of 141 treated patients (2.8%) were hospitalized, which was significantly less (p<0.001) compared with 58 of 377 untreated patients (15.4%) (odds ratio 0.16, 95% CI 0.06-0.5). Therefore, the odds of hospitalization of treated patients were 84% less than in the untreated group. One patient (0.7%) died in the treatment group versus 13 patients (3.5%) in the untreated group (odds ratio 0.2, 95% CI 0.03-1.5; p=0.16). There were no cardiac side effects.
Like I said, the apparent improvements brought about by the cocktail in patients given it early are massive. With result numbers this large, you do not need thousands of participants to clearly see the improvements. To argue that this study is of no value is nuts. I fully understand there are limits to what may be assumed in a retrospective study, but certainly these results are encouraging enough to suggest a full scientifically valid trial is warranted.
The majority of studies of HCQ did not include the two essential ingredients: zinc and commencing the treatment early in the disease progression. For this reason, the majority of studies of HCQ are irrelevant regarding the potential of the cocktail containing zinc being given early in the disease progression.
Fairy Modfather: thread locked until tomorrow morning or @Right_Said_Fred unlocks it first. This discussion is unproductive. --ggr
The locking of the thread and the time we spend here divided between political and scientific issues suggest the possibility that the scientific discussions and debates should be protected - well maybe that's a lost cause, but as much as possible protected - from the politics and the divisiveness of the political debate. Would it be possible to have this current thread continue to be a political discussion thread and a new thread started where serious science and discussion of scientific findings would be the principle currency. Here's what I posted in the market politics thread:
The coronavirus thread looks like it's locked and is not coming back. I would vote for the following idea: political implications of the coronavirus crisis can be posted here but I'm going to try to start a new thread that's dedicated only to coronavirus science. This means epidemiology, biology, treatment, vaccinations, Public Health implications, and any other treatment or medical dimension to the crisis, including the psychological impact of the crisis, while political posts particularly any version of covid-19 denial should be considered inappropriate. Who would be interested in such a separation of content?
I think part of the problem is that the political debates have partially submerged discussion of the science - in the current environment it's virtually impossible to have a discussion of the science that is not politicized by some actors. It shouldn't be that way, and it is an indication of the destructive polarization taking place everywhere, but science even though it's always influenced by politics, should be about weight of evidence, not the popularity of a meme.
Would a new thread titled Coronavirus Science: Epidemiology, Public Health, Biology, Treatment, and Vaccination be something that should be split off from the current thread which has been perhaps hopelessly politicized. Political debates could stay in the current thread? What do people think?
The coronavirus thread looks like it's locked and is not coming back. I would vote for the following idea: political implications of the coronavirus crisis can be posted here but I'm going to try to start a new thread that's dedicated only to coronavirus science. This means epidemiology, biology, treatment, vaccinations, Public Health implications, and any other treatment or medical dimension to the crisis, including the psychological impact of the crisis, while political posts particularly any version of covid-19 denial should be considered inappropriate. Who would be interested in such a separation of content?
I think part of the problem is that the political debates have partially submerged discussion of the science - in the current environment it's virtually impossible to have a discussion of the science that is not politicized by some actors. It shouldn't be that way, and it is an indication of the destructive polarization taking place everywhere, but science even though it's always influenced by politics, should be about weight of evidence, not the popularity of a meme.
Would a new thread titled Coronavirus Science: Epidemiology, Public Health, Biology, Treatment, and Vaccination be something that should be split off from the current thread which has been perhaps hopelessly politicized. Political debates could stay in the current thread? What do people think?
You can do that, but is there much to say about the science that isn't just a reply to the political posturing? New findings and new legitimate studies come only occasionally. I'd hope that everyone knows by now that masks, hygiene, vitamins C and D, distancing, and isolation are necessary to keep the virus from spreading.
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