Thread by @GidMK

A large, well-done observational trial just found a big mortality benefit for ondansetron in the treatment of COVID-19

I think this is a fascinating case study in how we use observational research
academic.oup.com/ofid/article/8…

The authors used a huge database of people who'd been treated for COVID-19, and looked at the associations between mortality and 84 drugs or drug classes

They found that metformin, nicotine, fluticasone, SNRI, expectorants and ondasetron reduced the risk of death from COVID-19, but given the potential for residual confounding only focused on ondasetron

The main conclusion is that we should probably try ondasetron as a treatment for COVID-19 in RCTs, which I think is justifiable based on the study

But I think the really interesting part is the initial analysis. It looks like if you test 84 medications for benefit in COVID-19 mortality, 6 positive results will be found

Thing is, we've been using studies a LOT worse than this one to drive treatments for the whole pandemic. The initial use of ivermectin, HCQ etc in 2020 was based on much less robust evidence than this research

Why is this interesting?

I think it shows just how important RCTs of interventions for COVID-19 are

If you test a bunch of drugs, you'll see some positives

If 1,000 people run studies on their databases, and you only really see the positive results published, you'll get the false impression that these drugs work against coronavirus even when the evidence is not good at all

This is in no way a critique of this specific paper, whose authors appear to have done a fantastic job, but it is a pretty worrying note for the rest of us

Anyway, ondansetron is a cheap, low-side-effect drug available pretty much everywhere in the world, so if it works for COVID-19 it'd be a brilliant addition to the arsenal