As long as we're talking trials, a quick refresher on the single, solitary trial that bought remdesivir its EUA and eventual FULL APPROVAL might be fun.
The initial trial was to include 400 patients, and naturally they were looking for a reduction in mortality. Apparently, early on, it looked like there was a small reduction in mortality, but not enough to reach statistical significance. How do you turn a statistically insignificant reduction in mortality into a statistically significant one? SuperSize the trial!
https://www.fiercebi...rimary-endpoint
Gilead supersizes remdesivir trials, changes primary endpoint
Unfortunately, the minor reduction in mortality seen early on never reached statistical significance, no matter how much they expanded the trial. What to do? Change the primary end point (on the fly!).
Don't have evidence for this, but Del Bigtree said when they expanded the trial, they actually ran out of placebo. Apparently remdesivir is not crystal clear like saline, so they had a placebo sauce mixed up to look like remdesivir and loaded into identically shaped bottles, with both remdesivir and placebo masked and labeled with numbers. Though the trial is always called a "double blind & randomized placebo controlled trial" at some point this ceased to be. They couldn't get more of the placebo sauce made up quickly enough when they expanded the trial, & doctors & researchers now knew who was getting remdesivir, & who wasn't.
Here's where things get interesting. The trial was suddenly truncated! Fauci explained that they had suddenly seen an improvement in recovery demonstrated by shorter hospital stay, and for ethical reasons the trial was halted, as it was determined it would no longer be ethical to continue the placebo arm of the trial once the drug was found to be helpful.
Interestingly, time to hospital discharge can vary quite a bit from week to week, which would give a strong motive to truncate the trial when hospital discharge for the remdesivir arm was statistically positive. If you ran the trial to completion, there was a chance the hospital discharge numbers might not have reached statistical significance on the day the trial was to officially have ended. Since the trial was no longer blinded (after they ran out of placebo), anyone could have easily seen the perfect point to truncate and score a WIN!
Fauci got his remdesivir EUA, and came out looking like a saint for halting the trial to save the placebo arm with his magic potion.
The WHO announced the results of their own RCTs on October 15th, stating: "The evidence suggested no important effect on mortality, need for mechanical ventilation, time to clinical improvement, and other patient-important outcomes."
Just a week later (Oct 22), the FDA granted full approval to remdesivir, which remains the only COVID specific drug in the CDC guidelines. I found this rather peculiar, as the WHO opinion was based on 4 different RCTs, involving many more patients than the NIH/NIAID trial.
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Amazing how little evidence it takes to get a money making pharmaceutical an EUA, and even full approval, and just how difficult it is to even allow front line doctors working in the field to even prescribe existing generics off-label.
We live in interesting times!
Edited by Dorian Grey, 27 July 2021 - 09:16 PM.