> there were 141 deaths in the control arm, a 47.6 percent mortality rate
That seems very high to me. I checked quickly for data, and I found a study[0] showing mortality rates for hospitalized covid patients in the U.S. between from 9% to 15%.
So where did they find a control group with 47.6% mortality? Is care that much worse in Brazil vs. the U.S? Are they only giving this to mortally ill patients? The claim of 92% efficacy depends on this very high control group mortality.
>So where did they find a control group with 47.6% mortality? Is care that much worse in Brazil vs. the U.S?
Yeah, unfortunately it is -- 38% according to this news piece, 80% for ICU patients[1]. It makes sense that it is even higher in Amazonas, the Brazilian state reported in the study. Over there they had a very serious health system collapse the last few months; even oxygen supplies were completely depleted statewide for a couple of weeks.
I think it's going to depend very much on the distribution of patients with the different WHO Covid Ordinal Scale categories within the cohorts.
If there were a lot more 5s (severely ill hospitalised patient on non-invasive ventilation or high-flow oxygen) vs. 3s (hospitalised patients not needing oxygen therapy), it would presumably make a large difference.
Summarizing, it looks like the TMPRSS2 protein is necessary for the virus to replicate, and the Androgen Receptor modulates its transcription.
But where I'm confused is why this drug in particular was studied, instead of an approved AR antagonist like bicalutamide or enzalutamide. Way easier to dispense those than some clinical trial drug, right? And is it important that the drug is a silent antagonist of AR rather than an inverse agonist?
Also, how does this affect women? Are we at less risk of mortality through this mechanism? My T levels are very low, but all of us have androgens and their receptors. Maybe TMPRSS2 gets transcribed even when T or DHT levels are low?
Generally with specialized papers we've found that it's best to link to the best third-party article and then have a link to the paper in the thread. Unfortunately the third party article often isn't great, but it's at least an easier place to get some context, and we can replace the URL when people point out a better one.
This is great news and an amazingly strong outcome! Proxalutamide is an antiandrogen, which reduces some of the effects of androgens including testosterone, so I wonder if this has a stronger effect in males than in females. Although the paper mentions the sex distribution of the patients, it doesn't seem to mention the details necessary to conclude this, but unless I'm mistaken over something trivial I'm unsure as to why. Anyone have any thoughts?
This is an antiandrogen. Androgens are thought to play a role in COVID, and apparently there is a "high prevalence of androgenic alopecia in hospitalized patients with COVID-19".
Also callled "male-pattern baldness" but affects both sexes.
What split is optimal depends on what effect size you expect. If you expect a very large effect, you get more statistical confidence from allocating more subjects to the treatment group.
On the other hand, if your treatment is very costly, adding subjects to the control group may be an effective way to increase study power without as much increase in study cost.
(Intuitively, I'm not an expert) Apart from the statistical reasons already mentioned, there is also an ethical one. If you expect the study to confirm the treatment to be highly beneficial, you prefer not to withhold it from your patients.
Here is an extreme example: suppose you are an HIV skeptic who believes that AIDS is not caused by the HIV virus but rather by drugs [1]. How large a study would you need to falsify your hypothesis?
Answer: one HIV-positive subject, left untreated, would be enough, if that person were otherwise healthy. If that person died of AIDS, that would leave one of two possibilities:
1. HIV causes AIDS, or
2. Something else causes AIDS and that person JUST HAPPENED to have that other causal factor AND a (harmless) HIV infection.
The odds of #2 are low (because AIDS and HIV infections are both uncommon) so that just leaves the first possibility.
As a side-note, that experiment was actually done by an HIV skeptic, on both herself and her unfortunate daughter [2]. Needless to say, both are now dead.
Medications for people with rare conditions tend to be astronomically priced (attempting to recover r&d costs from few buyers?). Covid doesn’t seem to be particularly rare
I guess the need is so much more at this point that the cost of producing the drug matters much more. Anyways, it can't be too expensive to produce to be practical, because the valuation of the company increased by billions of dollars.
That seems very high to me. I checked quickly for data, and I found a study[0] showing mortality rates for hospitalized covid patients in the U.S. between from 9% to 15%.
So where did they find a control group with 47.6% mortality? Is care that much worse in Brazil vs. the U.S? Are they only giving this to mortally ill patients? The claim of 92% efficacy depends on this very high control group mortality.
[0]: https://jamanetwork.com/journals/jamainternalmedicine/fullar...