Composite endpoints and the component doing the work

Composite endpoints and the component doing the work Writing it up because I had to work it out twice and would rather nobody else did.

I have seen SURPASS-4 (Lancet, 2021) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows.

My reading is that the trial is sound for its own question and is being stretched to answer a different one. I might be wrong about that, which is why this is a topic rather than a correction.

What I would like from this discussion: someone who disagrees with me to say why, with the section of the paper they are relying on.

Picking up the opening post: that is the part I would want checked first.

Absolute numbers, not just relative: a 30% relative reduction tells you the ratio but not the practical magnitude. The event rate in each arm and the difference between them tells you how many people benefit.

Intent-to-treat versus per-protocol: ITT includes everyone assigned regardless of whether they took the drug. Per-protocol includes only those who completed it as intended. The two can give substantially different results.

Multiplicity and multiple comparisons: if a trial tests many hypotheses, the chance of a false positive on at least one by random chance increases. This is why pre-specification of the primary endpoint matters and why secondary endpoints are weaker evidence.