A trial’s primary endpoint is the single outcome it is built around, such as the change in a depression score at week 6. It sets the sample size and is named in advance, usually in a public registry. Other measures are secondary endpoints. Testing many of them raises the chance that one looks positive by luck.
Psilocybin trials show why the distinction matters. In a 59-person trial against escitalopram, the primary outcome showed no significant difference, while secondary outcomes favoured psilocybin but were not corrected for multiple comparisons (Carhart-Harris et al., 2021). The 2026 EPISODE trial missed its primary endpoint, so its secondary results were treated as exploratory (Mertens et al., 2026). In a 233-person trial, sustained response at 12 weeks was a secondary endpoint (Goodwin et al., 2022).
When reading a headline, check whether the reported result was the primary endpoint. A positive secondary result after a missed primary one is a lead for future trials, not a finding. Preregistration makes outcome switching easier to spot.
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