https://www.nejm.org/doi/full/10.1056/NEJMoa2012410
Conclusions
In this
observational study involving patients with Covid-19 who had been
admitted to the hospital, hydroxychloroquine administration was not
associated with either a greatly lowered or an increased risk of the
composite end point of intubation or death. Randomized, controlled
trials of hydroxychloroquine in patients with Covid-19 are needed.
(Funded by the National Institutes of Health.)
#FAIL
ReplyDeleteThis drug has been nothing but a distraction so far.
Hopefully the newbs who took a sudden interest in pharmaceuticals thanks to Trump touting this potential medicine are learning the lesson of history in medicinal chemistry that the vast majority of hunches and intriguing hypotheses simply fail in patients. It is rare that something works, and you don't know it works from small uncontrolled and low quality studies like the open label French (Raoult) nonsense. Those are just hunches that then need to be tested. So far it's looking really ugly for this touted miracle cure.
You are the biggest FAIL of all
ReplyDeleteWhat a crybaby. The truth is what matters, not your feelings about me.
ReplyDeleteThe NEJM study has only 9_10% white patients (non Hispanic) and we don't know what age they were. Also, 5 days treatment, not enough.
ReplyDeletePerhaps elder whites in care homes, or in satmar community fare better.
All I'm saying is this study is inconclusive.
and therefore?
ReplyDeleteThe observations coming out now are that blacks, and other non whites have a 2-4x higher fatality rate from covid19 than whites do.
ReplyDeleteThe limitations in the study are that they only treated patients for 5 days, and whites are underrepresented in the study.
Other studies with longer treatments have shown better results. Interesting that they found no detrimental effects of this drug either.
If a drug doesn't benefit the people who suffer and die from the virus, then the drug is useless in treating that virus.
ReplyDeleteBlacks are "over represented" in this trial only because more blacks showed up to the hospital with covid infections. They took a sampling of all the hospitalized cases that had occurred and did a retrospective analysis on the outcomes with whatever treatments were given (HCQ vs. no HCQ).
You're really resorting to "targeted medicine" now and suggesting that hydroxychloroquine will be a drug that can only treat patients of a certain racial composition effectively? And Magic Satmar Genetics? LOL. This is getting beyond absurd now. It's not a targeted medicine and its purported MOA is indepedent of race or genetic diversity. This is just more post hoc nonsense to explain away failed trial results. More drawing of the bullseye around the arrows.
"Other studies with longer treatments have shown better results."
No, they haven't.
https://www.sciencedirect.com/science/article/pii/S0924857920300996
ReplyDeleteend point being 6 days, it is longer than 5 days.
You could point out that this trial has a smaller number of patients, which makes it weaker in drawing conclusions.
It is an unfortunate fact that blacks are dying at a disproprortionately higher rate than whites from covid 19, for reasons not yet known. Targetted medicine or not ( we call it personalized medicine), these are what have to be taken into consideration.
Satmar experiment hasn't published any scientific data, so it is only anecdotal at this stage.
Also, you confuse analysis of data with "drawing of the bullseye around the arrows". Now, at the end of the day , the NEJM study may be pivotal in burying HCQ for this disease, I am not stating that it factually is a cure.
That makes no sense. There is no logical rationale why this drug and its MOA would work differently in different races, and no one ever suggested that it does until trial results came out and now you are attempting to redraw the bullseye ex post facto. Testing in a higher risk cohort (such as by having more blacks in the study) makes the task of showing a stat sig benefit easier. You don't need to power the trial as much to show the benefit. The fact that it doesn't work in a higher risk cohort makes a stronger case that it doesn't work at all. Not a weaker case.
ReplyDeleteOnce again you are citing the same open label, non-randomized, non blinded trial by Raoult which aside from that type of trial being a weak form of evidence akin to anecdote, has also been criticized for its methodology and unreliable data interpretation! Raoult has a far from sterling reputation as a researcher. He is the reason Trump touted this medicine in the first place. It hasn't worked here. It hasn't worked anywhere, except in Raoult's open label studies with his very liberal forms of "data analysis"
It's time to turn the page. Raoult can tout this as a cure all day long, but it isn't one. It hasn't been a cure in hospitalized US coronavirus patients. Not even close.
And here is yet another failed trial, in NY hospitalized patients. Analyzed as retrospective cohort study by U Albany. And the combo once again proved dangerous for the heart!
ReplyDeletehttps://jamanetwork.com/journals/jama/fullarticle/2766117
Reported by cnn here https://www.cnn.com/2020/05/11/health/hydroxychloroquine-doesnt-work-coronavirus/index.html
There are a few different points and either you misunderstand my points or I am misunderstanding your responses, so let's try:
ReplyDelete1) I never claimed that HCQ definitely works, I only said there is some trial evidence that supports it.
2) "There is no logical rationale why this drug and its MOA would work differently in different races,"
Its MOA isn't fully understood, if it actually does have one. Furthermore, and more importantly, it is not at all understood why blacks, for example, have a much higher death rate from this disease than whites. The reasons, therefore could be very different from why elderly (white) are more susceptible than younger people. Hence your attempt above is not helpful to solving this condundrum.
Your higher risk cohort argument, is essentially a kal v'chomer, or a fortiori argument. But as I have explained, the risk in black people is not qualitatively udnerstood, whereas in elderly white (and others) it is generally assumed to be due to weaker immune system. So it is comparing apples with oranges, hence your argument (on its own) does not apply.
3) Raoult: You stated categorically that there are no such trials, and i cited one. So you are using the No true Scotsman fallacy - i.e. this is not a true clincial trial. But yes, it can be criticised as a poorly constructed trial.
4) Even with all these trials, they are still problematic, and the reason is that outcomes in hospitals are unpredictable and variable. ICUs have different death rates, from 50% to 90% depending on which hospital.
5) UK trial on HCQ now starting https://www.telegraph.co.uk/news/2020/05/11/drug-championed-donald-trump-trialed-uk-among-vulnerable-groups/
6) The "bullseye" claim is also false. I am pointing out a significant flaw in the trial data. It could be that with other ethnic groups, drugs work differently. This is frequently the case in Japan and China, compared to white caucasian patients. Just as an example, how many white people have sickle cell anaemia?
Raoult is an egomaniacal self-promoter so I don't accept his "research" and his cherrypicked results. I'm not saying this baselessly and I'm not engaging in a fallacy. I'm not going to copy and paste but you can read all about it here https://forbetterscience.com/2020/03/26/chloroquine-genius-didier-raoult-to-save-the-world-from-covid-19/
ReplyDeleteEven the society running the journal where that preprint/article appeared spoke against the research conduct and asserted the methodology was not up to basic standards. Aside from the fact that it is open label and non-randomized which makes it anecdotal and hypothesis-generating AT BEST (A hypothesis which has not been proven in any subsequent studies and if anything seems to be disputed by a host of studies). That's just a trial design and plenty of studies are run like that. Those are meant to be hypothesis generating. There isn't any foul committed in running something like that (only in an improper interpretation of its results! There is a foul in twisting it and concluding something not supported, as was done on Fox News). Even leaving that aside, there were ADDITIONAL PROBLEMS with this work in terms of cherry picking the results and excluding patients to make the numbers look better. That means that even the anecdotal "result" being touted was not really what was achieved.
It is HIS work that initially created the hype behind this medicine combo in the White House and Fox News. It is still this SAME WORK that you keep citing. They just add more patients. His work is not trustworthy in addition to being fairly useless from a trial design perspective. The "useless" and hypothesis-generating part isn't the misconduct. That's just weak evidence. The misconduct is the twisted interpretations and the cherry picked results to dress it up to something more than it was.
"Its MOA isn't fully understood, if it actually does have one. "
Huh? We know exactly what it's supposed to do. I love how now you are inventing mystery MOAs because the data went against you. You just resort to any straw you can grasp. You are basically making the argument this is a magic concoction that you are convinced a priori works against covid19, and so if blacks aren't helped, if NYC hospitalized aren't helped, if VA system patients aren't helped, etc etc well there must be some subset that it works on (because you concluded ahead of time that it works). That's not how medicine works, and what's sad to me is, I think you know that.
Doesn't the association of the combo of HCQ+ZPak, which is Raoult's magic formula, with an increase in cardiac arrest give you any sort of pause at all that hey maybe this isn't what was advertised??
ReplyDelete"You are basically making the argument this is a magic concoction that you are convinced a priori works against covid19, and so.."
ReplyDeleteNonsense, I'm not convinced it works, and I'm not an advocate of it. You are reading someone else's words into what I wrote. You may have an argument, but i never said it works nor implied that that is my beleif.
There are more trials with the drug, including here in UK - if they also fail then presumably that's the end of it.
Oh, well that is serious. why did they say no harm caused in the NEJM trial? Actually it is used for lupus and some other skin conditions, I will have to check with a cardiologist before i test it.
ReplyDeleteThere are other trials apart from Raoult's, which are mentioned in this piece
ReplyDeletehttps://www.genengnews.com/news/novartis-plans-phase-iii-trial-of-hydroxychloroquine-for-covid-19/
They are also small time and not well crafted trials. Novartis is going ahead with a Phase III trial according to the article. I am assuming that unless this current batch of trials provide better data, HCQ will be assigned to the Covid19 scrap heap.
How about the following - perhaps Remdesivir may not work well with African Americans but will work better with whites? I am not concluding anything ahead of time, but sadly there are sometimes genetic differences. If HCQ fails, it is not the drug I have pinned any hopes on - the probabilistic mountain keeps getting higher with trial, for it to have a Probability of Success.
Or perhaps what you saying - essentially that I am chasing my tail - is what is in fact being done by the trial sponsors in UK and also Novartis as well (as Pharma did in other disease areas, most recently Alzhemier's and beta amyloid plaques).
Yes it is used for other conditions, but read the drug label. There is risk of QT prolongation among other side effects. People who are prescribed this medication for lupus or RA are examined by their doctors and all the risks are weighed with each individual situation. I would think the patient's heart risk has to be evaluated.
ReplyDeleteThat type of personal and detailed evaluation isn't necessarily happening when you have a guy saying "yeah take this at first sign of sniffle" because he believes with all his heart that it helps against covid19. That is a more reckless approach. When it's being done in hospitals and where neglect to run RCTs to establish evidence, it's a similar idea (We think this, this, and this might work so throw everything against the wall and hope something sticks and saves this covid patient).
The QT prolongation effect is magnified when this drug is combined with Zpak.
The drug is almost buried for covid19. There is new drug repurposing eg antiviral cocktails+ interferon beta.
ReplyDelete