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Samuel Brown Profile picture
@DrSamuelBrown
Mar 23, 2020 • 3 tweets • 1 min read • Read on X
First randomized data about #Hydroxycloroquine for #COVID19. Too small to comment on anything except the fact that this IS NOT a miracle drug. kns.cnki.net/kcms/detail/33… (open in chrome and use translate function)
OK. Read it (G translate lets you use "file" for upload). N=30, hospitalized for COVID-19. 1/30 (in the HCQ group!) progressed to HFNC but not intubated. Not even the barest hint of a difference in any parameters. They used the virologically potent (Yao et al) dose of 400/d x5d.
So, you'll be surprised to hear that the appropriate next step is to perform real trials and in parallel look for other treatments.

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More from @DrSamuelBrown

Samuel Brown Profile picture
May 27, 2021
Just a couple thoughts from the realm of COVID-19 trials. 1. We are honestly very excited that fewer patients are afflicted by COVID-19. We will work as hard as we can to make sure trials are available to patients wherever they are in the world AND we will celebrate the fact that
this is becoming a rarer disease.

2. This really looks to be a disease of unvaccinated people now. It's striking how little ARDS we are seeing among vaccinated people. Not sure whether any specific line of evidence is helpful, but, wow. In the big COVID ARDS trial we're
running, about 90% of the patients are unvaccinated. There are the public health reasons to be vaccinated as well, but the clinical side of things -- preventing life-threatening disease -- is quite persuasive as well.
Read 4 tweets
Samuel Brown Profile picture
Feb 4, 2021
In case the story about full-dose anticoagulation in critically ill patients is confusing, a quick comment about the design and the reason what looks like harm is being called futility. Recall that in the prespecified Bayesian model, they used a threshold of 99% probability
that the OR was > 1 or < 1. This is an appropriate move. If you drop the probabilities lower, the Bayesian approach starts to look a lot more like an error-inflation machine. So if you're being rigorous, you want for 99% probability before you declare superiority or inferiority.
At the relevant interims, they met the 99% probability for superiority in the moderate (no organ failure) group, but they only had 98.5% probability of inferiority/harm in the organ failure/severe group. However, they had a futility bound that was clearly met, so they were able
Read 6 tweets
Samuel Brown Profile picture
Nov 11, 2020
I'm thinking more about the Pfizer vaccine (and grateful for those who have clarified some key points). First, I agree that early efficacy (right after the second injection) prevents infection in this patient population. That seems statistically certain.
Second, the population is those the investigator deems to be at high risk. I know that we've all wanted "wiggle room" in our inclusion criteria and that's not wrong. But for generalizability we want to know what "high risk" really means. In the event, it looks like "high-risk"
meant ~40/10,000 in the placebo group got COVID in the first month, versus ~4/10,000 (having to estimate because not enough detail in the news release). Note that (contra some bizarre innumeracy in Vox), this doesn't mean it fully protects 9 out of every 10 people who receive it
Read 10 tweets
Samuel Brown Profile picture
Nov 10, 2020
I've been hearing and thinking more about the Pfizer mRNA vaccine this morning. It does seem like this signal is likely to be real (there's not enough data in the news release to know, but most credible back calculations suggest that the efficacy signal is real). So I've been
trying to think what bothers me about it. And it's the ways that the culture of interim analyses seems to be shifting. Instead of the clear boundaries keeping the businesspeople from interfering with trials while they're being run, we're now seeing premature breaking of
that confidentiality for reasons that aren't entirely clear to me. I would hate for one of the legacies of the COVID pandemic to be that pharma gets to break the protections of interim analyses in order to beat their competitors in competition or sway the public. I can't wait
Read 4 tweets
Samuel Brown Profile picture
Nov 10, 2020
HAHPS trial also published--atsjournals.org/doi/abs/10.151…. I'm incredibly proud of @Research_Inter ability to run a pragmatic controlled trial in context of ORCHID to allow us to move more efficiently through candidate agents. There's an early suggestion that azithromycin may be
useful (looking forward to RECOVERY results in that regard). If anyone can remember back to March, there was a plan to provide HCQ with essentially no oversight, consent, or monitoring. With retrospect, HAHPS (and its sister trial HyAzOUT) were exactly the right response.
Based on the suggestion of a harm signal in trials and environments with minimal safety monitoring and open eligibility criteria and the entirely neutral effect seen in ORCHID, I believe that having HAHPS as a response to a public impulse to use unproven therapies outside of
Read 6 tweets
Samuel Brown Profile picture
Oct 18, 2020
Once a year I give a lecture to the 2d year medical students on humanizing intensive care. It's fun to be with these bright young people moving toward careers as physicians. One asked me an interesting and important question that seems like it's worth reflection.
Specifically, how do we engage people in positive and respectful ways if we don't have an authentic connection with the patient/family member? We know from RCTs that rote condolence letters after a death seem to raise and then disappoint expectations of intimacy, so how do we
support people without being ingenuine (and/or raising expectations we can't meet)? These questions resonate especially loudly in our modern cultural moment where authenticity is prized, and our radar is tuned to detect inauthenticity, especially among those with power.
Read 13 tweets

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