Placebo-adjusted

This is, in our opinion, the number most often misread in psychedelic coverage, and the misreading always runs the same way. A company reports how much patients on the drug improved, a reader hears a large figure, and the control arm never enters the sentence. Patients on placebo in depression trials improve too, sometimes substantially, so a big within-arm improvement can sit on top of an unimpressive drug effect. Only the distance between the two lines says anything about the compound. When we score our own published calls we score them on the placebo-adjusted difference for exactly this reason, and we say so before the number exists rather than after.

We glossed the term in Issue 11, while restating the scoring rule for a call made in Issue 10: "Placebo-adjusted is doing real work in that sentence. It means the gap between the two arms, not how far either arm improved on its own. Patients on placebo in these trials get better too, sometimes a lot better, and the only number that tells you anything about the drug is the distance between the two lines."

What does placebo-adjusted mean in practice? It means you need to know what the comparator was. Not every control arm is an inert placebo, and the difference matters more in this field than in most. In Issue 6 we separated Compass's two Phase 3 trials on precisely this point: COMP005 measured 3.6 points against an inert placebo, while COMP006's 3.8 points is 25mg against a 1mg dose of the same drug. Both are separations. They are not the same claim, and we wrote that COMP006 "does not, on its own, show the drug beats doing nothing."

The size of the gaps is the useful context. Across the readouts we have covered, the drug-versus-placebo differences on the depression scale used in these trials run from 3.6 points at the low end to 8.1 points at the high end. That narrow band is where the sector's arguments happen.