Alexandros Marinos 🏴‍☠️ Profile picture
Wannabe practical philosopher. Founded https://t.co/RmDxQ7Ka0d, currently working on $NEWTHING #OCCUPYUNIVERSE

Jul 11, 2022, 21 tweets

Biber finally published! Israeli study was circulating as preprint for quite a while. ijidonline.com/article/S1201-…

Let's do a mini review to compare and contrast. 89 patients, so a fairly small study, done done between May 2020 and Jan 2021.

Therefore the patients would be dealing with the original strain of the virus, mostly. Maybe some Alpha towards the end.

We see that the weights are fairly concentrated with the top quartile starting at 90kg.

...which is why the fairly limited dosing, about half the dosing of TOGETHER, would have been more likely to have shown an effect.

Note that they straightforwardly tell us that the patients got pills of the same appearance. TOGETHER did not make such a statement, nor have the authors clarified despite repeated calls. (Cc @FlavioCadegiani)

In the all important "time to symptom onset" category they were aiming up to 3 in the beginning, but had to extend upto 7 days. Given the slower replication of early variants, this may have been less crucial? Still, would be good to get a median value here, I can't see it.

On to the results. 3 hospitalizations in placebo, only one in treatment, discharged after a day. Given the fairly small size of the trial, this wouldn't be able to reach "statistical significance" levels.

In terms of the study primary endpoint, even with such a small patient population, it reached "statistical significance". Ivm reduced time of shedding, affected viral viability, showing antiviral activity.

Importantly, and this is something I've said often, ivm, needs to be tested under the same conditions other antivirals are. It doesn't need magic conditions, only fair ones.

When tested similarly to molnupiravir or remdesivir, its antiviral activity comes through.

All in all, here we have a study from a "western" country (Israel), which is out of the "high strongyloides" zone. How are we to explain this one away?
semanticscholar.org/paper/The-Glob…

Update on time from symptom onset: it's there, I'm blind.

Median 4 days, with top quartile starting at 5. So as far as we've seen, fairly small time, given how long PCR tests needed early on, and lower than TOGETHER, even though this is an unfunded study.

So, what might the critical voices say? Let's start with @slatestarcodex. He says it's a.. ""negative"" study?

WHAT?

Ah, but you see, the person who destroyed his article, @GidMK is "not a fan" (this is my shocked face). 😐

Scott says that they excluded patients with high viral load.

This appears to be (yet another) misunderstanding of Scott, who misread the confused objection of @gidmk. Let's dive deeper.

You see, HN found that they excluded patients with PCT Ct > 35 in the first two tests. Scott reads this as "high viral load". In fact it is the EXACT OPPOSITE. It's LOW VIRAL LOAD. The more cycles PCR needs to find your positive result, the LESS virus you have for it to analyze.

And since the study was focused on analyzing the effect of ivermectin on viral load, they excluded patients with low viral load.

BUT BUT BUT the pre-registration!!

Many tried to explain to @GidMK that he was misunderstanding his HUGE DISCREPANCY.

And really, if we're throwing away studies for violating pre-registration, what about TOGETHER changing the primary endpoint and merging two endpoints into one?

What about activ-6 not even reporting its pre-registered primary endpoint?

Rigor for thee but not for me, as usual.

Concluding, here's a positive study that shows quite encouraging results for ivermectin, done with parameters that are not quite comparable, but closer than the big studies to the patented antivirals in terms of dosing, time since symptom onset, in relation to the variant tested.

PS. Excellent thread by @AOlavarria worth clicking "translate tweet" on, for every tweet:

Worth noting that the trial took place in Sheba medical center, one of the world's top hospitals, ranked higher than Stanford, Brigham & Women’s, and Mount Sinai, amongst others.
(Thank you, anonymous tipster)
newsweek.com/best-hospitals…

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