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Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

medrxiv.org

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Re: Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

#341

Post by URSpider94 »

capnrefsmmat wrote: post #333
URSpider94 wrote: post #195

Earlier quoted context omitted.

This is not the bar that's typically applied for drug trials. The goal of a drug trial is not to prove beyond a shadow of a doubt that it DOESN'T work. The goal is to prove to a high level of confidence that it DOES work. For example, it's highly unlikely (roughly less than 2.5%) that HCQ reduces the onset of ARDS by half. If it ultimately turns out that HCQ reduces the rate of death by 5%, we'd have to do a tremendo…

To be clear, this claim > For example, it's highly unlikely (roughly less than 2.5%) that HCQ reduces the onset of ARDS by half. is not one that can be justified by frequentist statistics such as those used in the article. We can't make probabilistic claims like that unless we go Bayesian. Well-designed drug trials typically plan in advance to have the sample size necessary to detect an effect of clinical significanc…

Actually, I CAN make that claim based upon the data in the article. The relative risk [RR] of developing ARDS on HCQ vs. in the control group was 1.14, with 95% confidence interval of 0.65 - 2.00. That means that 95% of the time, the relative risk will fall between those two guardrails. If we take the single-sided probability, then the relative risk will be less 0.65 2.5% of the time. "Reducing the onset by half" means a relative risk of 0.5, which is less than the lower 95% confidence interval bound.

Re: Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

#342

Post by filleduchaos »

3fe9a03ccd14ca5 wrote: post #132
bcrosby95 wrote: post #111

And to put this interpretation into perspective, people that need this drug for diseases that it has proven to have a large effect on are losing access to it because it may or may not help with COVID-19.

HCQ is an off-patent drug that is produced in every major country in the world. In fact, many countries have stockpiles of it because of its efficacy at preventing malaria. If there’s a risk of a supply run, it would definitely not last very long. For many people there’s alternatives for treating arthritis and lupus. If it’s shown even to improve the patient’s outcome by even just 10% or more (as this study suggests)…

> In fact, many countries have stockpiles of it because of its efficacy at preventing malaria.

The world largely moved past quinine for battling malaria quite a while ago. In fact, chloroquine is all but banned in my country now.

Re: Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

#343

Post by giardini »

full title "No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen:..."

from the article:

"We used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day...

This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group).

The median age of patients was 60 years ..."

"...[Patients were from] four French tertiary care centres providing care to patients with COVID-19 pneumonia. Adult patients were eligible in this study if they were aged between 18 years and 80 years, had PCR-confirmed SARS-CoV-2 infection, and required oxygen by mask or nasal prongs (corresponding to a WHO progression score of 5)."

"Among the 181 patients eligible for analysis, 84 received HCQ within 48 hours of admission and 97 did not (although 8 of them did receive HCQ later on)."

So, first of all, these patients were infected with Covid-19 _days_ prior and now had progressed to pneumonia. The up to two-day delay in the administration of HCQ after admittance to the study is disheartening.

I am surprised that, despite the experimentors selecting an elderly, pneumonic, oxygen-dependent cohort in advanced stages of the disease, these patients did as well as they did. Its a credit to the human body.

But timing is everything...

Once a Covid-19 patient has developed pneumonia, it is too late for hydroxychloroquine to affect the Covid-19 virus' replication process significantly. The patient's body is saturated with the virus.

In a patient who has developed pneumonia the disease has progressed to a second phase wherein the virus and other opportunistic pathogens (e.g., bacteria) attack the lungs and other tissue. Antibiotics may help at this point. But it is quite clear that the patients in this study arrived too late to gain any benefit from hydroxychloroquine which, when coupled with zinc sulfate, slows or halts viral replication _early_ in the disease, delays or halts the virus' progress and allows the body time to develop an immunological response to the virus.

The study's conclusion states explicitly that " These results ... do not support the use of HCQ in patients hospitalised for a documented SARS-CoV-2 pneumonia."

So, the trick is to treat _early_ with HCQ+zinc sulfate+azithromycin.

Re: Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

#344

Post by dang »

bcrosby95 wrote: post #292
dang wrote: post #255

Earlier quoted context omitted.

(This subthread was originally a reply to https://news.ycombinator.com/item?id=22880291 )

You may as well delete it. My point was to caution against the continued enthusiam of using this drug for COVID-19 despite the consequences of doing so. The original article has no such problem. Yet the person I replied to could be interpreted as "wait, maybe its still good!". My comment makes zero sense as a reply to the original article.

That's why I included a pointer to your comment's original context.

This is mostly a technical problem of how comment trees that get extremely heavy having no natural way to divide themselves. Sometimes we prune them, and when we do that, we try to do it in a non-lossy way.

Re: Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

#345

Post by tptacek »

kazinator wrote: post #338
tptacek wrote: post #331

Earlier quoted context omitted.

I don't know you enough to call you "ghoulish" and wouldn't be inclined to, but the sentiment itself hopes that a treatment for an illness killing tens of thousands of people per week will fail in order to secure supplies for a chronic but nonfatal ailment. I feel like the absolute morality of that sentiment is something we can actually evaluate. (It's all hypothetical, of course, because in fact HCQ does not appear…

Have you considered that I might be thinking of the problem that it will be hoarded up by some individuals who have neither the illness nor the ailment? Few who needs it for any reason will be able to get their hands on it. That's my thinking, more or less.

Hoping a treatment for C19 won't work --- in essence, rooting for the virus --- is a bad look. That's as far as the analysis goes. And, again, it's a moot point.

Re: Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

#346

Post by Bendingo »

lalaland1125 wrote: post #181
SlowRobotAhead wrote: post #145

Earlier quoted context omitted.

As insane as that is. And how funny is it (at least to me) that this is only because Trump came down on one side initially. If he had come out saying exactly the opposite, that HCQ was bad and we should be skeptical, everyone hoping it doesn’t work now would be looking for the 10 person studies saying it totally works and defending its use. It’s almost beyond reason how hyper partisan this specific issue is.

The fundamental difference is that one side is backed by neutral experts such as Anthony Fauci and the other side has shown nothing but disdain for science in countless issues (global warming, evolution, election fraud, etc).

> neutral experts such as Anthony Fauci

Fauci isn't close to being a neutral expert.

Re: Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

#347

Post by apendleton »

Reelin wrote: post #324
apendleton wrote: post #237

Earlier quoted context omitted.

Yes, different arms will have data available at different times. The prophylaxis one might take longer than the others, but for the ones involving sick people, once they hit their target enrollment (which probably won't take long at all), those people will either get better or they won't.

I wouldn't expect a given prophylaxis case to take more than ~2 weeks to assess (the recommended quarantine time), and I would expect there to be significantly more eligible participants for that arm than the others. Am I missing something?

Prophylaxis is for people who are currently negative (it's pre-exposure, not post). You need to give them the medication (or a placebo) and then wait long enough for a significant fraction of each group to have had an opportunity to become infected, so you can meaningfully compare the trial group with the control group. They're all wearing PPE and such anyway (both groups), so not that many are going to seroconvert even in the control group in just a couple of weeks.

Re: Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

#348

Post by massaman_yams »

ajross wrote: post #116
massaman_yams wrote: post #79

Earlier quoted context omitted.

Politically, yes, there was/is a cargo cult. Both for those convinced it's a cure, and the anti-cargo-cult opposing party convinced it's somewhere between useless and actively harmful. From a medical practice standpoint, you have a widely-available drug with well-known side effects that can be administered in a medical setting with low risk, and potential life-saving upside. When the research is early but potentially…

> anti-cargo-cult opposing party convinced it's somewhere between useless and actively harmful. Can you name some prominent members of this cult and their statements that match this framing? Serious question. I don't think anyone really matches that description. Pretty much everyone horrified at the cloroquine boosterism was horrified because it was irresponsible and dangerous, not because they had strong feelings ab…

A handful of friends/acquaintances on fb - so, no, sorry. It's clear they're less informed than most, and I've certainly seen plenty of more appropriate responses along the lines of what you describe.

To clarify a bit: it's certainly not the position of the opposing party as a whole, but those I saw who were vehemently opposed to it were ideologically motivated.

Re: Study: No evidence of efficacy of hydroxychloroquine in hospitalized patients

#350

Post by Reelin »

apendleton wrote: post #347
Reelin wrote: post #324

Earlier quoted context omitted.

I wouldn't expect a given prophylaxis case to take more than ~2 weeks to assess (the recommended quarantine time), and I would expect there to be significantly more eligible participants for that arm than the others. Am I missing something?

Prophylaxis is for people who are currently negative (it's pre-exposure, not post). You need to give them the medication (or a placebo) and then wait long enough for a significant fraction of each group to have had an opportunity to become infected, so you can meaningfully compare the trial group with the control group. They're all wearing PPE and such anyway (both groups), so not that many are going to seroconvert e…

I don't see how any of this would increase the time to evaluate a given study participant beyond ~2 weeks? Regarding what you said about prophylaxis, the study page specifies that participants will either:

* Have had close contact with a known positive individual within the past 4 days (but not have any symptoms themselves yet).

* Have developed symptoms (and tested positive) within the past 4 days.

Technically that's not really a prophylaxis, but it's early enough that it's practically the same thing. It's also more representative of how we would be likely to employ the medication in the real world. (Also I don't see how it would be ethical to intentionally expose people, and waiting for people to be inadvertently exposed seems impractical for a number of reasons).

Edit: Whoops. I had slightly confused the smaller PATCH trial (https://clinicaltrials.gov/ct2/show/NCT04329923) and the larger University of Minnesota one (https://clinicaltrials.gov/ct2/show/NCT04308668). It looks like the PATCH trial is indeed only testing actual prophylaxis in healthcare workers, and specifies a two month period for each participant in the trial.

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