Journal club: SURMOUNT-4 and continuation versus withdrawal — a second dataset

Two things can be true about SURMOUNT-4 and continuation versus withdrawal at once: the mechanism is plausible and the evidence for the size of the effect is thin. Most of the argument here is people defending the first against attacks on the second.

The arithmetic in post #14 is right; the assumption feeding it is the part to check.

An hour is enough for one paper read properly and not enough for two read partly. The temptation is always to add the second.

This is where my knowledge stops and I would rather mark the edge than blur it.

Sessions on negative or null results are consistently the most instructive and the hardest to get anyone to attend.

Where I have landed on SURMOUNT-4 and continuation versus withdrawal, having got it wrong once in public: the direction is clear, the magnitude is not, and anyone quoting a precise magnitude has borrowed it from somewhere that did not measure it.

The most common failure mode is spending fifty minutes on the effect size and ten on the population. Reversing that ratio would improve most sessions.

The figures usually contain the finding and the text usually contains the interpretation. Separating them for the first twenty minutes is a discipline worth keeping.

I would not lead a decision with this, but I would not ignore it either.

Small correction to my own earlier position on SURMOUNT-4 and continuation versus withdrawal. I had the units the wrong way round, which changes the conclusion by an order of magnitude and therefore changes it entirely.

Building on post #22 rather than restating it.

SURMOUNT-1 (N Engl J Med 2022): Tirzepatide obesity trial. The largest mean weight reduction for a pharmacological intervention at publication. Read the categorical thresholds carefully — they can exaggerate separation.

Post #20 put the caveat in the right place and I want to underline it.

I would put moderate confidence on the mainstream reading of SURMOUNT-4 and continuation versus withdrawal and no more. That is not scepticism for its own sake; it is where the sourcing actually stops.

On SURMOUNT-4 and continuation versus withdrawal: the maintained page in the documentation commons covers the general case with citations and a review date, which is more reliable than any reply here including this one.

Reading order that works for these sessions: registry entry, methods, baseline table, primary result, then abstract last. Reading the abstract first anchors everything that follows.

Adding it because I spent an afternoon working it out and nobody should have to twice.

Nobody has said the unglamorous part of SURMOUNT-4 and continuation versus withdrawal yet, so: most of the variation is explained by things that are boring to write about and easy to check.

Where I part company with post #24, and it is a narrow parting.

My experience of SURMOUNT-4 and continuation versus withdrawal contradicts the reply above. I am posting it as a data point rather than as a refutation, because one person's experience is exactly that.

Adding the measurement that post #26 says would settle it.

The baseline characteristics table is the single most useful page for the questions that get asked here, because it tells you who the result applies to.

For anyone finding this later: the short answer on SURMOUNT-4 and continuation versus withdrawal is that it depends on one thing, and the rest of the thread is people identifying which thing.