Huge effect size doesn't matter at all when the effect is not the correct one. There is a significant risk that this surrogate endpoint is not telling the true story as the virus migrates to the lung, measuring in the throat could be very misleading.
> It has been reported that oral absorption of CQ and HCQ in humans is very efficient. In animals, both drugs share similar tissue distribution patterns, with high concentrations in the liver, spleen, kidney, and lung reaching levels of 200–700 times higher than those in the plasma10. It was reported that safe dosage (6–6.5 mg/kg per day) of HCQ sulfate could generate serum levels of 1.4–1.5 μM in humans11. Therefore, with a safe dosage, HCQ concentration in the above tissues is likely to be achieved to inhibit SARS-CoV-2 infection.
> We have a lot of experience. We have made the most precise description of an untreated patient cohort among the Munich patients. And at the Munich group, we saw how the virus concentration in both the throat and lungs behaved over time. And we can say that at the beginning of the disease the virus is in the throat and it goes away on its own through the - let's say - the first ten days of the disease. After that, many patients in the throat have little or only irregular evidence of the virus.
But that has nothing to do with how the virus behaves in the lungs. The virus is then really replicative in the lungs, especially in severe cases. And we can also say what the patient has in his throat, it has nothing to do with how the clinical development of the disease continues, whether the patient quickly gets well or only goes through a difficult phase. So what is being measured in this entire clinical study has nothing to do with the outcome of the disease, with the symptoms, but is only an initial indicator of how the disease starts. For all patients, the virus concentration drops in the first week, but if you now imagine that the group being treated will be included a little later and the untreated group being included earlier in this study, it is in nature the thing that with this group that was later included - they are already further in eliminating the virus from the throat - that the virus then goes down in the throat, faster. This disappears faster because they have simply been in the course of the disease for a long time. Whether this is due to the fact that they are treated, cannot be said at all from this entire study. Perhaps it would have been so if the groups had been put together as here, but if they hadn't given them chloroquine, but some headache pill, the study would have been the same.
The authors of this study excluded one patient from the study because they died, and several other because they were admitted to ICU.
Assuming the dead patient did not get run over by a car, not considering death as relevant information for your study seems... bold.
They switched outcomes from what they pre-registered.
They did not even measure viral load, their primary outcome, in the control group. They looked at the patient and went like “she’s really sick, that’s a 23 at least”.
This, and the other problems mentioned, make this study suspect. And at the point where actual fraud is a possibility, the top line numbers stop being meaningful.
So in that sense your comment is like my Grandmother’s insistence on Pascal’s wager: “I know there’s no God, but paradise sound too good not to try”
By the same logic, you must stop eating carrots if I tell you that doing so will be infinitely rewarded after you die.
They are not counting the 6 patients that they lost in the treatment group (1 just leave, 1 had too much nausea, 3 where transfer to ICU, 1 died). It is more strange that they didn't lost any patient in the control group.
Toxicity is typically tied to dosage rates or drug interactions. The bigger concern from the french study was the additional use of Azithromycin which is more dangerous/toxic. The dosage rates and toxicity of HCQ by itself is well known.
The other big risk is panicky people ignoring the recommended guidelines. Fortunately in the US (and Canada) both drugs require a prescription where both a doctor and pharmacist will provide this information, and it will be printed on the pillcase. What's more worrying is people buying it in countries where it's over the counter then not reading the side of the box and taking far too much (or worse reading the correct dose and thinking 2x the drug = 2x more effective or some nonsense).
Check out this analysis: https://twitter.com/AppleHelix/status/1240495937522368512
the goal of studies like this are to strengthen the evidence base and remove those unknowns, so physicians can make evidence-based decisions. if the study is sufficiently poorly designed, it does not accomplish this goal, and can even lead to misinformation
Your above-statement, and then the quote suggests you have no idea how this actually works in the real world. The reality is that NO-ONE KNOWS whether there is great efficacy, no efficacy, or marginal efficacy. No one. And we will not until we have a properly designed trial. That link direct us to is horrifyingly badly designed (well, not designed at all). There are all sorts of confounding issues in their results.
and r/coronavirus discussion https://www.reddit.com/r/Coronavirus/comments/fncs5c/didier_...
Quote:
> With my team, we believe we have found a cure. And in terms of medical ethics, I believe that I have no right as a doctor not to use the only treatment that has so far proven successful. I am convinced that in the end everyone will use this treatment. It's just a matter of time before people agree to eat their hats and say, this is the thing to do.
And in the Irish times:
>“In my field, I am a star, worldwide,” he boasted to La Provence newspaper.
>“I don’t give a damn what others think. I am not an outsider. I’m streaks ahead of the others.” https://www.irishtimes.com/news/world/europe/coronavirus-fra...
Not the most modest of guys...
It's difficult to due true double blind random studies in these cases because doctors are there to give everyone the best chance at recovery, not to pick half of a group to potentially do worse.
Hopefully we can ethically do well design studies on controlled groups with moderate symptoms, but until then this imperfect clinical data is very interesting.
But that's not what these doctors were doing, is it? They weren't looking at whether the patient got better or not. They were looking at viral load only.
https://twitter.com/GaetanBurgio/status/1241201751916568576
> Outcome from the study is based on viral load only and not on clinical outcome and I can see a major flaw here as clinical outcome critical.
https://www.medrxiv.org/content/10.1101/2020.03.16.20037135v...
> The proportion of patients that had negative PCR results in nasopharyngeal samples significantly differed between treated patients and controls at days 3-4-5 and 6 post-inclusion (Table 2). At day6 post-inclusion, 70% of hydroxychloroquine-treated patients were virologicaly cured comparing with 12.5% in the control group (p= 0.001).
The effect size is huge, even considering the potential biases.