How clinical trials work

Phase 1 asks whether a dose is tolerable, usually in a small number of healthy volunteers. Phase 2 asks whether it plausibly works in people who have the condition, and finds the dose. Phase 3 asks whether it works in a large population against a proper comparator, and it is the last step before a company can file for approval. Phase 4 happens after approval.

An early-phase result is a reason to run a bigger trial. It is not evidence that something works, and a great deal of psychedelic coverage treats it as though it were.

Every trial declares in advance the one measure it will be judged on. If a trial misses its primary endpoint it has failed, however encouraging the secondary measures look. Reporting that leads with a secondary outcome is usually reporting a failure politely.

A placebo-controlled trial works because neither side knows who got what. That is difficult with a substance whose effects are unmistakable: most participants correctly guess their assignment, which can inflate the apparent effect. Good trials use active comparators or low doses to blunt the problem, and honest ones discuss it.

Recruiting means the sponsor recorded it as accepting participants. Active, not recruiting means enrolment closed but the trial continues. Terminated means it stopped early, which is sometimes a safety signal and sometimes only funding. The registry does not always say which.