Chloroquine trials - Printable Version

Chloroquine trials - Printable Version

+- The CardBoard (https://thecardboard.org/board)
+-- Forum: Emergency (https://thecardboard.org/board/forum-11.html)
+--- Forum: Covid-19 (https://thecardboard.org/board/forum-12.html)
+--- Thread: Chloroquine trials (/thread-19212.html)

Pages: 1 2 3 4 5 6 7 8 9

RE: Chloroquine trials - cardcrimson - 04-12-2020

I'm perplexed. The thread is about chloroquine and it's effectiveness. Granted, the results are unproven but there are some glimmers that it is effective. Regardless, how does your claim that this could kill three million Americans fit into this discussion? Most projections are under 100k at this point.

(04-12-2020, 09:49 PM)dabigv13 Wrote: Spanish Flu only killed 2 to 3% of its victims, but was still one of the worst pandemics in history. If this kills 1% of the US population, which it could if we did nothing, that is 3 million, or approximately 2.5 times as many Americans died in the Civil War, WW1, WW2, and Vietnam put together.

RE: Chloroquine trials - dabigv13 - 04-12-2020

I was responding to your assertion that since most people get better, what's the big deal. You're the one that took it off the topic of chloroquine. If this thing kills 1% of the people it infects (a realistic number) and it infects most of the populace (a realistic possibility for a highly virulent virus such as this), that's millions. It can be less if we practice distancing, wear masks, etc. Many projections take some of these measures into account. It's already killed 22 thousand Americans and we are just getting to know this thing.

RE: Chloroquine trials - magnus - 04-12-2020

(04-12-2020, 10:13 PM)cardcrimson Wrote: Most projections are under 100k at this point.

100k is the number by August, i believe. Assuming we stay socially restricted.

Million+ is if we let this virus run through the whole population because we can't find a vaccine/treatment or find another way to halt it's progression.

RE: Chloroquine trials - 2006alum - 04-12-2020

(04-12-2020, 10:10 PM)dabigv13 Wrote: I don't think the people on here always worrying about the economy are trolling. I just think the possibility of hundreds of thousands or more dying in a span of months is too abstract to process. I hope that's what it is.

At this point, the debate has been rehashed endlessly, so asking that rhetorical question for the 30th-odd time doesn't seem like it's being asked in good faith.

What's done is done, so a more productive way forward is focusing on steps to "re-open" (whatever that means) the economy. One of those steps is finding potential treatments to lessen or even obliterate symptoms, but it doesn't sound like hydroxychloroquine is going to be a massive game changer based on everything I've read from sources that aren't based on highly motivated reasoning.

RE: Chloroquine trials - M T - 04-12-2020

I haven't noticed many stating positive results related to Chloroquine, but one did come out this week. I'm not in position to judge its quality: https://www.medrxiv.org/content/10.1101/2020.04.08.20057539v1 "none of patients treated with chloroquine developed severe pneumonia, though without significance (difference, 12.0%; 95% CI, -3.5% to 30.0%) by propensity score matching."

That report also did indicate that those with hypertension using ACE Inhibitors & ARB therapies had better outcomes than thosse that used other drugs.

RE: Chloroquine trials - dabigv13 - 04-12-2020

In the abstract they point out it doesn't reach significance. To see a difference with this medication in preventing mild cases from progressing to severe ones, you will need a large sample.

We'll get that data in due time. The longer we can distance and prevent exponential growth, the more data we will have on what treatments are efficacious. Anecdotally and from the literature, this med doesn't seem like a game changer.

RE: Chloroquine trials - 2006alum - 04-12-2020

(04-12-2020, 10:46 PM)M T Wrote: I haven't noticed many stating positive results related to Chloroquine, but one did come out this week. I'm not in position to judge its quality: https://www.medrxiv.org/content/10.1101/2020.04.08.20057539v1 "none of patients treated with chloroquine developed severe pneumonia, though without significance (difference, 12.0%; 95% CI, -3.5% to 30.0%) by propensity score matching."

That report also did indicate that those with hypertension using ACE Inhibitors & ARB therapies had better outcomes than thosse that used other drugs.

Hmm. Quoting the entirety of the findings section of this paper:

Quote:Findings: In this retrospective, observational cohort study involving 564 patients with confirmed COVID-19, hypertension was an independent risk factor for progression to severe pneumonia irrespective of age and those on angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy were less likely to develop severe COVID-19 pneumonia, while nonspecific antivirals or chloroquine did not have significant impact on clinical progression.

Am I misunderstanding what this would constitute "positive results related to chloroquine"?

RE: Chloroquine trials - cardcrimson - 04-13-2020

(04-12-2020, 10:22 PM)dabigv13 Wrote: I was responding to your assertion that since most people get better, what's the big deal. You're the one that took it off the topic of chloroquine. If this thing kills 1% of the people it infects (a realistic number) and it infects most of the populace (a realistic possibility for a highly virulent virus such as this), that's millions. It can be less if we practice distancing, wear masks, etc. Many projections take some of these measures into account. It's already killed 22 thousand Americans and we are just getting to know this thing.

It wasn't my assertion at all. Somebody posted this:
"Here's the thing, for the vast majority of people with this disease, they will get better with or without treatment."
Seems like the author was implying exactly what you're accusing me of. . . .

RE: Chloroquine trials - BostonCard - 04-13-2020

(04-13-2020, 08:08 AM)cardcrimson Wrote:
(04-12-2020, 10:22 PM)dabigv13 Wrote: I was responding to your assertion that since most people get better, what's the big deal. You're the one that took it off the topic of chloroquine. If this thing kills 1% of the people it infects (a realistic number) and it infects most of the populace (a realistic possibility for a highly virulent virus such as this), that's millions. It can be less if we practice distancing, wear masks, etc. Many projections take some of these measures into account. It's already killed 22 thousand Americans and we are just getting to know this thing.

It wasn't my assertion at all. Somebody posted this:
"Here's the thing, for the vast majority of people with this disease, they will get better with or without treatment."
Seems like the author was implying exactly what you're accusing me of. . . .

Two things can be true simultaneously. The majority of people will get better, and, in fact, only a minority will even require a hospitalization... and to quote one of the presidential candidates, this is a big f-ing deal.

In context, what it means is that any uncontrolled study (of any drug) is very hard to interpret. In the early days of modern medicine, penicillin did not undergo a randomized, placebo controlled study. But that's because it was given to moribund patients with infections raging through their body, who almost certainly would have died. When the drug cured them in a couple days (ah, the days before antibiotic resistance), it was obvious that penicillin was effective to treat life threatening infections. You more or less know what the counterfactual would have been like, so rigorous testing with a placebo was not necessary. To this day, we still have some drugs that are tested that way, though these are often for rare indications where very few people have the disease and the outcome is almost universally fatal (and well-characterized).

However, when you have an illness that "only" kills a 5% of those who are hospitalized, if you see that most patients you give the drug get better, it is hard to know what would have happened in the counterfactual. Even if you treat enough patients to have expected one or two to have died, you don't know if you were "lucky", or if your study was biased in some way (for example, with entry criteria that excluded those most likely to die). For studies like that, you need a placebo to compare it to.

Fortunately, the WHO is testing chloroquine/hydroxychloroquine, and comparing it not only to placebo, but also to remdisivir, Kaletra, and Kaletra plus interferon.

https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments

BC

RE: Chloroquine trials - BostonCard - 04-13-2020

https://www.nytimes.com/2020/04/12/health/chloroquine-coronavirus-trump.html

Yikes, chloroquine trial in Brazil was halted over cardiovascular complications.

Here's a link to the original trial: https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1

BC

RE: Chloroquine trials - BostonCard - 04-14-2020

Some shade thrown.

https://www.nejm.org/doi/full/10.1056/NEJMp2009457?query=RP

BC

RE: Chloroquine trials - oldalum - 04-14-2020

(04-14-2020, 06:46 PM)BostonCard Wrote: https://www.nejm.org/doi/full/10.1056/NEJMp2009457?query=RP

Another reason for limiting "compassionate use" is that it makes clinical trials more difficult to conduct and take longer, because most patients when given the choice between a 50% chance of getting a drug in a placebo-controlled trial and getting it under compassionate use will choose the latter, regardless of whether or not a President touts it (the fact that it is being studied suggests to the patient that someone has reason to think it might be effective, which in medical research is called equipoise.). Also decreases the randomization and the generalizability of those trials, although that effect is probably negligible in most cases.

RE: Chloroquine trials - akiddoc - 04-15-2020

(04-14-2020, 06:46 PM)BostonCard Wrote: Some shade thrown.

https://www.nejm.org/doi/full/10.1056/NEJMp2009457?query=RP

BC

This is why we will have to depend on other countries for real data on drug evaluation.

RE: Chloroquine trials - oldalum - 04-15-2020

And another problem with widespread compassionate use of hydroxychloroquine: it complicates the conduct and interpretation of trials of other investigational treatments because people want to be on hydroxychloroquine. article

RE: Chloroquine trials - BostonCard - 04-15-2020

This is an overblown "problem". The reason you do a randomized, controlled trial is that a patient on hydroxychloroquine has an equal chance of landing in the treatment arm as in the control arm. If you do it properly, roughly the same proportion of patients in each arm of your trial winds up having had HCQ so the effect evens out.

BC

RE: Chloroquine trials - BostonCard - 04-20-2020

Novartis is starting a large, randomized, three armed phase III clinical trial of hydroxychloroquine ± azithromycin versus placebo.

https://www.novartis.com/news/media-releases/novartis-sponsor-large-clinical-trial-hydroxychloroquine-hospitalized-covid-19-patients

BC

RE: Chloroquine trials - BostonCard - 04-21-2020

Here's a study that shows that the risk of death was actually more than twice as high in the hydroxychloroquine arm than in the usual care arm:

https://www.medrxiv.org/content/10.1101/2020.04.16.20065920v1.full.pdf

Quote:In this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone.

That being said, there is a major problem with the study in that the study was not randomized, so it is possible, if not likely, that sicker patients were given hydroxychloroquine than those given usual care (confounding by indication). From the article:

Quote:Our study has certain limitations including those inherent to all retrospective analyses such as non-randomization of treatments. We did, however adjust for a large number of Covid- 19-relevant confounders including comorbidities, medications, clinical and laboratory abnormalities. Despite propensity score adjustment for a large number of relevant confounders, we cannot rule out the possibility of selection bias or residual confounding.

So, I'm still going to wait till the WHO's or Novartis' clinical trials read out to determine whether HCQ is effective. But we can probably rule out a "game-changing" effect size, or it would have overcome any confounding by indication.

BC

RE: Chloroquine trials - 2006alum - 04-21-2020

(04-02-2020, 09:17 PM)martyup Wrote:
(04-02-2020, 07:28 PM)OutsiderFan Wrote: The top medical minds and scientists in the world would have coalesced around the drug being a legit difference maker if it really is. Every one I have heard or read talk about it have been quite skeptical.

The top medical minds in the world are recommending it and have said that they would take it if they got sick.

This seems not to be the case, after all...
[tweet]https://twitter.com/nprpolitics/status/1252704946706841600?s=20[/tweet]

RE: Chloroquine trials - BostonCard - 05-07-2020

This is an observational (not randomized) study, but they looked at 1446 patients, so if it were a whopping effect, you would have seen it.

https://www.nejm.org/doi/full/10.1056/NEJMoa2012410?query=RP

Quote: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.)

The hydroxychloroquine patients were sicker at baseline (confounding by indication), but they matched with a technique called propensity scoring. Here's what their survival curves looked like.

[Image: nejmoa2012410_f2.jpeg]

It is clear that chloroquine/hydroxychloroquine is not the "game changer" that the President claimed it was. I really wish he would stick to his core competency of reality show hosting, rather than snake oil salesmanship.

BC

RE: Chloroquine trials - fullmetal - 05-07-2020

I assume the shaded areas are confidence intervals or error bars...not much to choose between there.