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Comment by notfed | Hacker News Reader

If that's true, I'm confused how this is a "double-blind, randomized, controlled trial"?

Also, what's up with drug studies always having such a low sample size? Is it really that hard to find people who'd volunteer to get free drugs?

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> Also, what's up with drug studies always having such a low sample size? Is it really that hard to find people who'd volunteer to get free drugs?

They try to make for no comorbidities and and for MDD that is pretty rare. It also means that we’re often studying rare configurations compared to those commonly seen in actual practice. Statistics doesn’t like confounding elements and humans are very confounding. So either you get “bad” statistics, or you get “bad” data. And why you have front line drugs that only have a helpful effect for 33% of people.

Just to add one minor detail to this very good explanation: even if you could find 500 participants matching the criteria instead of 50, you wouldn’t want to “waste” all of them on your first study design.

> If that's true, I'm confused how this is a "double-blind, randomized, controlled trial"?

Those are design descriptions.

Double blind means that neither patient nor the one administering the treatment knows which is which. Randomized only means that each subject is assigned randomly a treatment group. Controlled trial just means that the study design made sure that other variables that are not under experiment are also under control. Nothing about this preclude actions done to the subjects nor sample sizes.

Its expensive. Statistically speaking its really not that small. You can always argue p hacking but these are always useful as a means to do further research

Often you’re not allowed on your medication for any of your other health issues.

We need a new approach to randomly controlled trials.

I propose a new approach: Rather than given treatment vs not given treatment, we instead vary the dose slightly, and we include the whole world in the trial.

Ie. instead of taking 100mg of Advil, instead you will receive somewhere between 95mg and 105mg of Advil. You won't be told how much you got - but the barcode on the box will encode that info. That already might be the case due to allowed inaccuracies, but now we're gonna measure and record it.

Later, the data of which box was dispensed is combined with any other relevant medical records, and across the hundreds of millions of people involved, any benefit/disadvantage of a small increase or decrease in dose will become apparent.

This doesn't sound very helpful

I mean it sounds like a way to trick people into letting a giant company build a surveillance system, and I imagine aliens observing humans in this moment in history might conclude that's what we want, but for science or the benefit of the people "surveyed" it's mostly downsides

That's not generally how drugs work. There's wide margins on how much dose is required for clinically significant results. Not only is the 110 pouns petite woman taking the same dose of aspirin as a 400lb elite powerlifter, but the effects can't be quantified in high resolution. The woman can't say her pain was 5% less than the powerlifter, and they can't say their pain was 5% more.

TBH there's no way to have a double blind trial of drugs like psilocybin (Scott Alexander has written a little bit about this [1] with respect to controlled trials for MDMA), for any reasonable dose size of psilocybin. Both the patient and the person administering the drug will become very aware, very quickly, if they're in the psilocybin group.

1: https://slatestarcodex.com/2017/06/05/is-pharma-research-wor...

This is wrong. You can absolutely dose psylocybin at levels that make a meaningful difference in experience (certainly enough to have an anti-depressant effect) without “tripping” or being in any way impaired. For many adults, this will be around 100-200mg of psilocybin.

Microgram, not milligram, of psilocybin. 100mg of psilocybin would be about 50-200 grams of dried cubensis mushroom.

There have been studies on microdosing, but it’s also valuable to know what happens at perceptible doses as well. It’s certainly a different experience.

It's not a question of impairment, it's a question of whether you come to some determination of whether you are in the control group or not.

Unsurprisingly, the way around it is to introduce a third treatment or fourth, with classical psychedelic 5-HT2 action. There are a few such choices and some are also registered antidepressants, one being DXM/bupropion, another being an ergoloid derivative or a psychedelic amphetamine like DOM.

But then you need to run a trial in a hundred or two hundred N.

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