What does SOUL tell me about constipation at the 7 mg dose?

What I have: SOUL · constipation · 7 mg.

This is presented as though it settles something, and I am not convinced it does.

I have two documents that appear to disagree, which is what prompted this.

What is the correct interpretation, and what is the common misreading?

Only what the 7 mg arm reported, and the denominator is that arm rather than the trial. Adverse-event tables are published per arm, so the 7 mg incidence of constipation has its own numerator and its own denominator, and pooling it with the other arms produces a figure that describes nobody. Two further deductions before you use it. Subtract the placebo arm — constipation occurs in people who received nothing, and the difference is the part attributable to the drug. And check whether SOUL counted events or counted participants: one participant with six episodes is one row in a participant count and six in an event count, and the two get quoted interchangeably. Nothing here is medical advice.

Start with what the trial was powered for. Everything else in the publication is secondary, exploratory, or a subgroup, and those three words mean three different things.

Intention-to-treat and per-protocol analyses answer different questions. ITT asks what happens if you offer the treatment; per-protocol asks what happens if it is taken as directed. The gap between the two is a measure of how tolerable the protocol was.

On the detail: a composite endpoint is only as informative as its least serious component. Where a cardiovascular composite combines death, infarction and stroke, ask which component moved, because they are not interchangeable outcomes.

Read the protocol and the statistical analysis plan if the result matters to you. Both are usually published alongside.