Hard Data on Remdesivir, and on Hydroxychlorquine
blogs.sciencemag.org
blogs.sciencemag.org
I'm undecided on whether HCQ is effective or not, but attempting to discredit it with shitty science is a large part of why people don't "believe science".
It’s not just about doses or timing. It doesn’t work.
This being shitty science has no bearing on whether HCQ works on not, but does relate to why people distrust the medical research establishment.
https://www.nejm.org/na101/home/literatum/publisher/mms/jour...
A lot of this HCQ stuff feels like God of the Gaps Theory at this point; as potential use cases are conclusively eliminated, so is the field of where it is "thought to work". Thought by whom, precisely?
March 30: https://www.clinicaltrials.gov/ct2/show/NCT04326725?cond=COV...
March 30: https://clinicaltrials.gov/ct2/show/NCT04326725?term=zinc&co...
April 6: https://clinicaltrials.gov/ct2/show/NCT04334512?term=zinc&co...
May 8: https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v...
May 1: https://clinicaltrials.gov/ct2/show/NCT04370782?term=zinc&co...
The people who created and executed these studies wanted to save lives. They created a method they thought would be most likely to work, and time and time again they didn’t. Different dosages, different timing, different places. No benefit.
The fact that people aren’t running more studies is not because there is a global conspiracy. It’s because the drug doesn’t do anything and researchers don’t want to waste their time and their patients lives satisfying critics who don’t care about the science.
Does HCQ work if you have some magic combination of zinc? Maybe. Is that more likely than another treatment given that HCQ has been heavily studied and shown no benefit and zinc had been heavily studied for a lot of things and shown no magical properties? Probably not. So researchers spend their time on things more likely to work.
> You came up with those parameters conveniently after the study was published.
> The fact that people aren’t running more studies is not because there is a global conspiracy.
> satisfying critics who don’t care about the science
> magic combination...magical properties
It seems like you've suddenly made a sharp u-turn from a good-faith discussion into crazy town. I thought we were hashing out differences, and now you're suddenly accusing me of making up excuses, believing in a global conspiracy, being anti-science, and thinking zinc is somehow a miracle drug. I think I should end the conversation here.
https://www.nejm.org/na101/home/literatum/publisher/mms/jour...
This term alone makes me highly skeptical. Honest researchers shouldn't be "pro" or "anti" anything. Coronavirus doesn't have an opinion on HCQ. It is a virus that either responds biologically to HCQ in vivo or it doesn't. Pro or anti are political terms that change the conversation from scientific to propaganda based.
If the research indicates that HCQ has a powerful prophylactic effect against Coronavirus in a double blind study, then let the data speak for itself.
However saying that you're "pro-HCQ" or "anti-HCQ" immediately discredits you in my eyes because viral pandemics don't have emotions and therefore can't care whether you are pro or anti anything.
It's not political, we're trying to find something that works.
Honestly I don't really get this at all. Not even a little bit. Why? Anyone who actually has a motive (like a company trying to make money) should be kept far away from the regulators that oversee the study, and the whole point of double blind trials is to keep self interested bias away from the result of a study where lives are literally at stake.
Isn't the point of a clinical intervention to save lives? Either the intervention saves lives or it doesn't. The researchers should be selected from people who can maintain a neutral viewpoint. If that is impossible their neutrality should still be maximized and biases should be eliminated as much as humanly possible.
Simply accepting that bias as a matter of course is imo the worst way to approach it.
> Isn't the point of a clinical intervention to save lives?
Why do you think saving lives can't be the motive? If you do a study, and conclude based on that study that a treatment works, you're supposed to remain "neutral"?
Let me put it this way, I wouldn't want to receive treatment from a healthcare provider who is "neutral" about the surgery they are about to give me, I want them to have a positive informed opinion based on experience, studies, etc.
A scientific researcher is trying to answer an unanswered question dispassionately. I don’t see how taking a bias in testing a scientific hypothesis can possibly determine the truth of a scientific fact.
Are researchers who say that applying leeches won’t cure cancer bad for cancer patients? Why shouldn’t they be hopeful that leeches cure terminal cancer, rather than being downers? The answer is that cancer is the enemy, not people who oppose medical treatments that don’t work.
> Honestly I don't really get this at all. Not even a little bit.
It's ok for scientists to think something's true before they have all the evidence lined up - especially in a predominantly empirical field like medicine. That's how new ideas happen.
Have you ever encountered someone who is motivated by altruism? Someone who is motivated by getting the truth out there?
Certainly a scientist can say "I very much hope that HCQ is an effective cure for Coronavirus" but that is very, very different from being "Pro-HCQ".
When I hear "Pro-HCQ" that implies to me a very strong suggestion of treatment, i.e. - "You should take HCQ as a treatment for Coronavirus infection", which is extremely different from, "I hope that the research shows that HCQ will be an effective treatment for Coronavirus, and I am doing a study with the goal of showing that this is the case".
Does that make sense?
I think that middle option is actually how a scientist would interpret the phrase. I can see why a layman would read it otherwise, though.
Doctors and scientists need to be objective. Advocating a treatment before the data is there, or cherry picking results is not science.
I found the tone in this last paragraph to be a little off-putting in its finality and unwillingness to consider further studies:
> I’m not in a mood to be subtle. Hydroxychloroquine treatment for coronavirus does not work. It is not beneficial, and in fact appears to be actively harmful. As far as I’m concerned, administering it to infected patients now constitutes medical malpractice. I have no interest in goalpost-moving efforts to say that they didn’t administer zinc or azithromycin, or they picked the wrong patients or the wrong loading dose or whatever. No. This is special pleading, and it is not backed up by any hard data. None of the countries or regions where HCQ was enthusiastically adopted, with or without the addition of zinc, azithromycin or what have you have seen discernable benefits. It. Does. Not. Work. Give it up.
Depending on the other paragraphs in the article it could go both ways.
It's the article this entire discussion thread is about.
Politicians completely ruined this particular word combination for me.
My reflexive interpretation is that things were exactly the opposite of clear and the speaker is likely to be lying.
Doctors are very clear that HCQ is too dangerous to give to people unless those people are very ill.
You not understanding this balance between risk vs reward doesn't make the science shitty.
HCQ has been used for 60 years for malaria, lupus and autoimmune diseases.
Please, stick to what you know and leave medicine to specialists.
Wikipedia doesn't make you a doctor.
I will be stealing this line.
Honestly I could use “Wikipedia doesn’t make you a lawyer” even more frequently.
There are also quite a lot of other HCQ studies, many with azithromycin and some also given very early before significant symptoms appeared (see one example here: https://www.nejm.org/doi/full/10.1056/NEJMoa2016638). They also didn't find any benefit to HCQ.
The insistence on these very specific criteria is just blatantly moving the goalposts. There simply isn't enough indications that HCQ works, and plenty of evidence that it doesn't to justify even more large studies than it already got. This is arguably a huge misallocation of resources based on very flimsy initial evidence.
Don't really have a dog in this fight, but my understanding is that pro HCQ doctors believe that zinc must be included with HCQ --it's not "moving the goal posts" if doctors aren't arguing that HCQ alone is a cure. However it does sound like moving the goal posts if it HCQ is bad because it is not alone a cure.
In a study of 932 patient cases, researchers at New York University Langone Health found that the addition of zinc to hydroxychloroquine and azithromycin was associated with a decrease in mortality in patients who were not admitted to the intensive care unit. [1]
[1] https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v...
I'm not sure what you're saying. Are you critiquing the study for not measuring and supplementing zinc in the HCQ cohort?
But there was further research showing HCQ mechanism doesn’t actually do anything so HCQ studies lost steam because they were a waste of time and effort.
Well, they do now, but that only seemed to emerge after it became clear that Raoult's (zinc-free) protocol didn't work.
"mortality by Day 29 for these patients was 11.4% with remdesivir therapy as compared to 15.2% with the controls."
"HCQ-treated patients did not survive better than those not getting the drug: 27% of them died within 28 days, versus 25% in the standard of care group."
Those mortality rates are clearly indicative of a strongly biased test group, even if they call it randomized.
The normal mortalit rate for Covid-19 is about 0.5% for the general population, and even if you can discuss that and say that is is closer to 3% in some areas, it is not 15% and not 25%.
Those studies are about the effect of remdesivir and HCQ for terminally ill patients.
"We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection." [1]
"In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality." [2]
These trials are explicitly about treating hospitalized patients, which is of course a group with a higher mortality than the general population. Nobody is saying otherwise. Remdesivir is administered intravenously, so it is unlikely you would try to deliver it to people with mild or asymptomatic infections. The comparison between the drugs in the general population would be very hard to do for that reason. Severe illness due to SARS-CoV-2 is such a huge problem that I'm not sure who would instead investigate a drug specifically for mild cases.
[1] https://www.nejm.org/doi/full/10.1056/NEJMoa2007764?query=fe...
[2] https://www.nejm.org/doi/full/10.1056/NEJMoa2022926?query=fe...
https://www.nhs.uk/news/medication/effectiveness-of-tamiflu-...
> It found that both drugs shorten the symptoms of influenza-like illness by about half a day in adults (but not in asthmatic children), compared to a placebo. There was no reliable evidence that either drug reduces the risk of people with flu being admitted to hospital or developing serious complications such as pneumonia, bronchitis, sinusitis or ear infection. Used as a preventative measure, Tamiflu and Relenza slightly reduced the risk of developing the symptoms of flu. The review also found no evidence that these drugs can stop people carrying the influenza virus and spreading it to others.
> The study also found that Tamiflu slightly increases the risk of adverse effects such as nausea, vomiting, psychiatric and kidney problems in adults, and vomiting in children.
The trial was done on hospitalized patients who obviously have a much higher mortality rate than patients overall. That’s the correct population to be studying, because that is the population that would receive the drug. It is administered intravenously.
None of this is indicative of bias on the results. It is the correct way to do clinical trials.
The problem is that they are implying that absence of positive effect on a late treatment on very ill patients can be extrapolated.
This is not the case.
I don’t see any reason for anyone to assume that the trial was done on a random subset of the population. That would be a irrational way to do drug trials, and it makes no sense to assume they are done that way.
This is not what is being tested here, and this is why studies like this one are misleading.
The title should be explicit: HCQ does not show better outcome for patients when administered late.
So this is NOT the correct population to be studying.
"You can see that these were indeed at-risk patients – the overall mortality rate in the general population for coronavirus infections is nowhere near those rates, and it’s a damn good thing it isn’t. The mean age of the patients was 59 years, 64% male, with 50% of them having hypertension, 45% of them obese, and 30% with Type 2 diabetes. So even though they were characterized as mild-to-moderate on enrollment, this was just the sort of group that you’d worry about as a physician."
It is still a valuable study even if it is not a study done on the general population.
[0] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
https://investors.chromadex.com/news/news-details/2020/Chrom...
It shows that Nicotinamide-Riboside (sold as TruNiagen) with a couple of common vitamins reduced time to recovery by about 30%. This is about the same result as the much touted remdesivir.
But while remdesivir is a very serious and expensive drug with serious side effects that has to be administered in a hospital setting under the oversight of a physician, TruNiagen is sold as an over the counter anti-ageing supplement, costs about $1.30 for a daily dose and there are no known adverse side effects (AFAIK, and according to the label).
Of course the two things aren't exclusive, you can take both remdesivir and truniagen. Furthermore, the truniagen study was a phase 2 study with 100 patients with mild to moderate symptoms, while remdesivir has been studied for a lot more patients and more seriously ill patients too. (There was no mortality data on the truniagen study, it seems that everyone survived.)
Nevertheless, 100 patients is plenty to make the study statistically significant. And considering how low the cost of actually taking truniagen is, I think this study is really important and really positive news in the fight against covid.
Again, it is criminal that the media is ignoring it. Truniagen is made by a small company with negligible advertising budget, while other Covid drugs and vaccines are made by massive pharma companies that regularly spend enormous amounts of money on mass media advertising. So perhaps this has something to do with this.