7 ms·

A shame, since the Lancet paper has problems[1][2] in particular related to the baseline of the HCQ-treated vs non-HCQ treated patients. And by admission of the

A shame, since the Lancet paper has problems[1][2] in particular related to the baseline of the HCQ-treated vs non-HCQ treated patients. And by admission of the authors themselves, it is not a substitute of a RCT. And this before the results of the Minnesota trial are out. At this point I hope those are negative, so that it does not show that countries are overreacting. [1] https://statmodeling.stat.columbia.edu/2020/05/25/hydroxychloroquine-update/ https://statmodeling.stat.columbia.edu/2020/05/25/hydroxychl... and related posts [2] https://twitter.com/StevePhillipsMD/status/1263899569252896771 https://twitter.com/StevePhillipsMD/status/12638995692528967... PS: The title is misleading. The ban is on the use on severe diseases, not all of them, according to the text in the news.

orwin 6y ago
Yes, i'm not a proponent of HCQ, not without RCT as some of my previous post might tell you, but the "raw" data of the Lancet study seems pretty well harmonized for raw data, i wouldn't trust this study for my national policies. I can't take HCQ as i already have extrasystole and a allergies treatment that already can cause arythmia, so i hope this won't be the "best" treatment, but really this paper, while interesting, should not be used to take decisions.
- lbeltrame 6y ago
  As I wrote elsewhere (check my post history) I personally think that if the effect is there, it is small. I don't really mind if HCQ doesn't work, but I get mad when people say "follow the science", and the most basic thing to do for science (a RCT) is not done. Let's see if the U of Minnesota trial is published soon. The PI of the study tweeted he had sent revisions to the manuscript, and hoped for a publication this week (and he however added that he thought the same last week).
  - tialaramex 6y ago
    > most basic thing to do for science (a RCT) is not done. Randomised Controlled Trials are the gold standard but not the "most basic thing". They are the ideal we'd like to have but often simply aren't an option. One of the most obvious reasons we often can't do a trial is that we have good reason to believe it would be unreasonably dangerous, which is why these trials stopped. The opposite scenario happens sometimes too. If all patients treated with Hydroxychloroquine magically got better they'd stop the trial and recommend immediately using it on similar patients.
pen2l 6y ago
Lancet isn't the only paper that has raised issues with HCQ treatment. Sciencemag [1] has this to say: However, both HCQ and AZ have potential cardiac toxicity (QT prolongation, which can lead to fatal arrhythmia), and HCQ additionally has the potential for negative effects on the eye. Understanding risk-benefit ratios is paramount if these drugs are to become a standard of care for COVID-19. Several post hoc analyses carried out in the United States and Europe suggest modest benefit, at best, from HCQ monotherapy for COVID-19 patients; one large post hoc analysis among U.S. veterans suggests that there is harm to patients from HCQ. Given the mechanistic rationale but lack of well-designed clinical studies and potential for drug-induced toxicity, there is a key need for controlled, randomized trials to test the efficacy and safety of these drugs for COVID-19 patients. [1]: https://science.sciencemag.org/content/sci/368/6493/829.full.pdf https://science.sciencemag.org/content/sci/368/6493/829.full... I don't think it's a "shame" that some have decided to stop wtih HCQ when other viable treatments seem to have less concerning side-effects. Either way, we will know very soon with greater certainty as ongoing randomized trials finish up.
- lbeltrame 6y ago
  Most of these analyses were done in late-stage COVID-19 patients, when any antiviral won't work (same results with remedisivir, lopinavir/ritonavir/ribavirin), that's why the discussion won't stop. Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus. And guess what, no one (save the U of Minnesota trial, AFAICS) has done a RCT on that. EDIT: I think it's a "shame" because all analyses so far focused on the late-stage disease, as I said, and because hopefully real RCT results will be out soon (like, real soon, or so I hope).
  - mxcrossb 6y ago
    It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. Such a large percentage of people recover on their own that even a very effective drug has limited returns. And of course you need the infrastructure to detect the disease early and deliver huge supplies. It makes me worry that all antivirals we try will fail.
cataflam 6y ago
> PS: The title is misleading. The ban is on the use on severe diseases, not all of them, according to the text in the news. And the RCTs are still going and will finish, unless there is a major negative effect noticed in them, which is not the case so far.
- lbeltrame 6y ago
  Indeed, there is hope that a definitive answer will come out (at this point, given how politicized the discourse is, any answer in either direction willl be fine). FTR, the U of Minnesota trials used normal dosages and (according to its PI) did not report any cardiotoxicity so far.
  - Yoric 6y ago
    Did they report any improvement?
    - lbeltrame 6y ago
      IMO, very responsibly, they will disclose their results only after peer review and publishing. I know their paper was revised and is under review.
acallaghan 6y ago
If it had any effect on covid-19, it'd be very obvious by now. There isn't some massive conspiracy here, it just doesn't work. The reason trials have stopped is because France, Italy, Belgium & the UK have seen worse outcomes generally, directly because of it. I don't get the 'it needs to be taken before symptoms!' argument - like we can possibly give a immunosuppressant with non-negligible side-effects (e.g. arrythmia) to billions of people with no scientific evidence of it working on covid at all.
- zackees 6y ago
  It HCQ doesn't work, why is it the common first line of defense used internationally? Why does scholar.google.com list so many papers showing that it's effective?
  - ceejayoz 6y ago
    Because it's a highly effective and widespread malaria (and RA/lupus) treatment?
    - vixen99 6y ago
      The dose for malaria is 200mg. It's the higher doses that are associated with heart arythmia in covid patients. According to a trial reported in https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-018-1188-2 https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s129... "No serious cardiac adverse effects were recorded in malaria clinical trials of 35,548 participants who received quinoline and structurally related antimalarials with close follow-up including 18,436 individuals who underwent ECG evaluation." "Chloroquine is the most widely used antimalarial drug in history. It has a terminal elimination half-life of one month and an annual consumption of hundreds of tonnes for over 50 years, so it may be the drug to which humans have been exposed to most. Despite producing consistent QT prolongation, the only case reports of TdP and sudden death have been for its use for non-malaria indications such as systemic lupus erythematosus or rheumatoid arthritis, where high doses are used for much longer than in malaria treatment, or in overdose"
halflings 6y ago
Agree this isn't an RCT, but why would this be an "over-reaction"? It's not like the default reaction is to administrate millions of doses of a medicine that has yet to be proven effective. (and could potentially do more harm than good) The studies supposedly proving HCQ's effectiveness have much bigger caveats (tiny sample size and/or manipulation of the groups in a dishonest way, like Raoult removing severe cases from the treatment group whereas the control group had none)
lenkite 6y ago
“India has so far made the right decision on HCQ and that this decision has been based on evidence,” Preeti Sudan, Secretary, Ministry of Health and Family Welfare, was quoted as saying by The Hindu. The government late last week extended the use of HCQ for paramilitary and police personnel involved in COVID-19 management, besides direct health care providers for positive patients. Soumya Swaminathan, Chief Scientist at WHO also told The Hindu that WHO is not advising stopping all HCQ trials but has only dropped HCQ from the Solidarity Trial, and that many prophylaxis trials using HCQ are ongoing or about to start.

orwin 6y ago

Yes, i'm not a proponent of HCQ, not without RCT as some of my previous post might tell you, but the "raw" data of the Lancet study seems pretty well harmonized for raw data, i wouldn't trust this study for my national policies. I can't take HCQ as i already have extrasystole and a allergies treatment that already can cause arythmia, so i hope this won't be the "best" treatment, but really this paper, while interesting, should not be used to take decisions.

lbeltrame 6y ago
As I wrote elsewhere (check my post history) I personally think that if the effect is there, it is small. I don't really mind if HCQ doesn't work, but I get mad when people say "follow the science", and the most basic thing to do for science (a RCT) is not done. Let's see if the U of Minnesota trial is published soon. The PI of the study tweeted he had sent revisions to the manuscript, and hoped for a publication this week (and he however added that he thought the same last week).
- tialaramex 6y ago
  > most basic thing to do for science (a RCT) is not done. Randomised Controlled Trials are the gold standard but not the "most basic thing". They are the ideal we'd like to have but often simply aren't an option. One of the most obvious reasons we often can't do a trial is that we have good reason to believe it would be unreasonably dangerous, which is why these trials stopped. The opposite scenario happens sometimes too. If all patients treated with Hydroxychloroquine magically got better they'd stop the trial and recommend immediately using it on similar patients.

pen2l 6y ago

Lancet isn't the only paper that has raised issues with HCQ treatment. Sciencemag [1] has this to say: However, both HCQ and AZ have potential cardiac toxicity (QT prolongation, which can lead to fatal arrhythmia), and HCQ additionally has the potential for negative effects on the eye. Understanding risk-benefit ratios is paramount if these drugs are to become a standard of care for COVID-19. Several post hoc analyses carried out in the United States and Europe suggest modest benefit, at best, from HCQ monotherapy for COVID-19 patients; one large post hoc analysis among U.S. veterans suggests that there is harm to patients from HCQ. Given the mechanistic rationale but lack of well-designed clinical studies and potential for drug-induced toxicity, there is a key need for controlled, randomized trials to test the efficacy and safety of these drugs for COVID-19 patients. [1]: https://science.sciencemag.org/content/sci/368/6493/829.full.pdf https://science.sciencemag.org/content/sci/368/6493/829.full... I don't think it's a "shame" that some have decided to stop wtih HCQ when other viable treatments seem to have less concerning side-effects. Either way, we will know very soon with greater certainty as ongoing randomized trials finish up.

lbeltrame 6y ago
Most of these analyses were done in late-stage COVID-19 patients, when any antiviral won't work (same results with remedisivir, lopinavir/ritonavir/ribavirin), that's why the discussion won't stop. Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus. And guess what, no one (save the U of Minnesota trial, AFAICS) has done a RCT on that. EDIT: I think it's a "shame" because all analyses so far focused on the late-stage disease, as I said, and because hopefully real RCT results will be out soon (like, real soon, or so I hope).
- mxcrossb 6y ago
  It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. Such a large percentage of people recover on their own that even a very effective drug has limited returns. And of course you need the infrastructure to detect the disease early and deliver huge supplies. It makes me worry that all antivirals we try will fail.

cataflam 6y ago

> PS: The title is misleading. The ban is on the use on severe diseases, not all of them, according to the text in the news. And the RCTs are still going and will finish, unless there is a major negative effect noticed in them, which is not the case so far.

lbeltrame 6y ago
Indeed, there is hope that a definitive answer will come out (at this point, given how politicized the discourse is, any answer in either direction willl be fine). FTR, the U of Minnesota trials used normal dosages and (according to its PI) did not report any cardiotoxicity so far.
- Yoric 6y ago
  Did they report any improvement?
  - lbeltrame 6y ago
    IMO, very responsibly, they will disclose their results only after peer review and publishing. I know their paper was revised and is under review.

acallaghan 6y ago

If it had any effect on covid-19, it'd be very obvious by now. There isn't some massive conspiracy here, it just doesn't work. The reason trials have stopped is because France, Italy, Belgium & the UK have seen worse outcomes generally, directly because of it. I don't get the 'it needs to be taken before symptoms!' argument - like we can possibly give a immunosuppressant with non-negligible side-effects (e.g. arrythmia) to billions of people with no scientific evidence of it working on covid at all.

zackees 6y ago
It HCQ doesn't work, why is it the common first line of defense used internationally? Why does scholar.google.com list so many papers showing that it's effective?
- ceejayoz 6y ago
  Because it's a highly effective and widespread malaria (and RA/lupus) treatment?
  - vixen99 6y ago
    The dose for malaria is 200mg. It's the higher doses that are associated with heart arythmia in covid patients. According to a trial reported in https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-018-1188-2 https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s129... "No serious cardiac adverse effects were recorded in malaria clinical trials of 35,548 participants who received quinoline and structurally related antimalarials with close follow-up including 18,436 individuals who underwent ECG evaluation." "Chloroquine is the most widely used antimalarial drug in history. It has a terminal elimination half-life of one month and an annual consumption of hundreds of tonnes for over 50 years, so it may be the drug to which humans have been exposed to most. Despite producing consistent QT prolongation, the only case reports of TdP and sudden death have been for its use for non-malaria indications such as systemic lupus erythematosus or rheumatoid arthritis, where high doses are used for much longer than in malaria treatment, or in overdose"

halflings 6y ago

Agree this isn't an RCT, but why would this be an "over-reaction"? It's not like the default reaction is to administrate millions of doses of a medicine that has yet to be proven effective. (and could potentially do more harm than good) The studies supposedly proving HCQ's effectiveness have much bigger caveats (tiny sample size and/or manipulation of the groups in a dishonest way, like Raoult removing severe cases from the treatment group whereas the control group had none)

lenkite 6y ago

“India has so far made the right decision on HCQ and that this decision has been based on evidence,” Preeti Sudan, Secretary, Ministry of Health and Family Welfare, was quoted as saying by The Hindu. The government late last week extended the use of HCQ for paramilitary and police personnel involved in COVID-19 management, besides direct health care providers for positive patients. Soumya Swaminathan, Chief Scientist at WHO also told The Hindu that WHO is not advising stopping all HCQ trials but has only dropped HCQ from the Solidarity Trial, and that many prophylaxis trials using HCQ are ongoing or about to start.