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This is not a typical drug trial. Typical trials are designed to have a large enough sample size that they will be able to detect any effect big enough to be c

This is not a typical drug trial. Typical trials are designed to have a large enough sample size that they will be able to detect any effect big enough to be clinically important. Here, they just went with the sample size they had available (understandably), which was so small that only a very large effect could be clearly established. It is completely wrong to interpret the lack of a statistically significant effect with this small sample size as showing that the drug doesn't work. Consider the result regarding transfer to ICU or death: 20.2% patients in the HCQ group were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group (16 vs 21 events, relative risk [RR] 0.91, 95% CI 0.47-1.80) The best estimate is for 9% less risk from using the drug, with the possibility of the drug cutting the risk by more than half not being excluded in the 95% confidence interval. Of course, the possibility that the drug actually makes things worse is also not excluded, but this can certainly not be characterized as proving that the drug doesn't work.

URSpider94 7y ago
I have no problems with the way this test was set up. It was a quick study that would have told us quickly if there was a huge benefit from HCQ. That wasn't the outcome. Larger tests with better statistical power will tell us if there is a smaller positive effect. My point is, the smaller the beneficial effect, the larger the test will have to be to find it, but also the lower the overall benefit to patients. Again, note also that more patients on HCQ were diagnosed with ARDS, so if you pick a different measure, you get the opposite result.
- jamesblonde 7y ago
  My immediate reaction was that I would not expect to see an effect if you are giving HCQ to patients after they have been hospitalized by the virus. You are now into the inflamation/cytokine storm phase of COVID-19. The best chance of HCQ working is very early, ideally before or directly after exposure. The jury is still out if you take HCQ after the onset of sympthoms if that is also too late. Based on this in-vitro study - https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0 - if I hypothetically had both Chloroquine (CQ) and Hydroxychloroquine (HCQ), I would prefer HCQ for prophylaxis/pre-sympthoms, but if I was sympthomatic, I would choose CQ. The loading time or HCQ is longer and it appears less effective at higher MOIs "the data suggest that the anti-SARS-CoV-2 activity of HCQ seems to be less potent compared to CQ, at least at certain MOIs."
  - tptacek 7y ago
    For pre-symptomatic C19 patients, we're already doing a large-scale natural experiment, because HCQ is part of widespread protocols for common ailments like RA, and the dosages those patients get are comparable. As I understand it: we're admitting lots of RA patients with C19; there doesn't seem to be a huge effect with early dosages either?
    - Gibbon1 7y ago
      Problem with that is people with RA and Lupus are typically hyper careful about their health and most likely to be serious about self isolating.
      - tptacek 7y ago
        I'll track down the source I read this from, but my claim was specifically that we are hospitalizing people with RA on HCQ already. So that doesn't really respond to what I said.
    - jamesblonde 7y ago
      Yeah, it's pretty clear there isn't a huge effect. But there may still be a big enough effect to move the needle. I have no knowledge of the RA/Lupus subgroup, so any anecdotes to share are welcome!
  - Reelin 7y ago
    > The best chance of HCQ working is very early, ideally before or directly after exposure. Adding to this, there are at least two reasonably sized ongoing trials of HCQ with appropriate randomization and blinding in North America alone (I believe there are a number of others elsewhere). I would encourage everyone to withhold judgement until either they post results, or a similarly reliable alternative data source appears. Target size of 3000 (https://clinicaltrials.gov/ct2/show/NCT04308668 https://clinicaltrials.gov/ct2/show/NCT04308668). Target size of 400 (https://clinicaltrials.gov/ct2/show/NCT04329923 https://clinicaltrials.gov/ct2/show/NCT04329923).

URSpider94 7y ago

I have no problems with the way this test was set up. It was a quick study that would have told us quickly if there was a huge benefit from HCQ. That wasn't the outcome. Larger tests with better statistical power will tell us if there is a smaller positive effect. My point is, the smaller the beneficial effect, the larger the test will have to be to find it, but also the lower the overall benefit to patients. Again, note also that more patients on HCQ were diagnosed with ARDS, so if you pick a different measure, you get the opposite result.

jamesblonde 7y ago
My immediate reaction was that I would not expect to see an effect if you are giving HCQ to patients after they have been hospitalized by the virus. You are now into the inflamation/cytokine storm phase of COVID-19. The best chance of HCQ working is very early, ideally before or directly after exposure. The jury is still out if you take HCQ after the onset of sympthoms if that is also too late. Based on this in-vitro study - https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0 - if I hypothetically had both Chloroquine (CQ) and Hydroxychloroquine (HCQ), I would prefer HCQ for prophylaxis/pre-sympthoms, but if I was sympthomatic, I would choose CQ. The loading time or HCQ is longer and it appears less effective at higher MOIs "the data suggest that the anti-SARS-CoV-2 activity of HCQ seems to be less potent compared to CQ, at least at certain MOIs."
- tptacek 7y ago
  For pre-symptomatic C19 patients, we're already doing a large-scale natural experiment, because HCQ is part of widespread protocols for common ailments like RA, and the dosages those patients get are comparable. As I understand it: we're admitting lots of RA patients with C19; there doesn't seem to be a huge effect with early dosages either?
  - Gibbon1 7y ago
    Problem with that is people with RA and Lupus are typically hyper careful about their health and most likely to be serious about self isolating.
    - tptacek 7y ago
      I'll track down the source I read this from, but my claim was specifically that we are hospitalizing people with RA on HCQ already. So that doesn't really respond to what I said.
  - jamesblonde 7y ago
    Yeah, it's pretty clear there isn't a huge effect. But there may still be a big enough effect to move the needle. I have no knowledge of the RA/Lupus subgroup, so any anecdotes to share are welcome!
- Reelin 7y ago
  > The best chance of HCQ working is very early, ideally before or directly after exposure. Adding to this, there are at least two reasonably sized ongoing trials of HCQ with appropriate randomization and blinding in North America alone (I believe there are a number of others elsewhere). I would encourage everyone to withhold judgement until either they post results, or a similarly reliable alternative data source appears. Target size of 3000 (https://clinicaltrials.gov/ct2/show/NCT04308668 https://clinicaltrials.gov/ct2/show/NCT04308668). Target size of 400 (https://clinicaltrials.gov/ct2/show/NCT04329923 https://clinicaltrials.gov/ct2/show/NCT04329923).