Revisiting: Journal club: SURMOUNT-1, read without the press release

On the subject in the title: Revisiting: Journal club: SURMOUNT-1, read without the press release Working notes rather than a conclusion.

Session topic: SURMOUNT-1 (N Engl J Med, 2022). Please read it before posting; the discussion is much better when everyone has.

The question I would like us to start with is what the trial set out to estimate, rather than what it found. Once that is on the table we can talk about whether the design could have answered it, and only then about the numbers.

Specific things I would like covered: the population and how far it generalises, how discontinuation was handled, whether the comparator was a fair one, and what the absolute rather than relative effect looks like.

I will summarise at the end and the summary will feed the relevant digest page.

Two people in this thread mean different things by SURMOUNT-1 and are disagreeing about the definition while believing they are disagreeing about the facts. Worth pausing to define it.

Confirming post #2 from a second method, which matters more than confirming it from a second person.

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

I had written a reply contradicting the opening post and deleted it. Here is what survived.

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

The arithmetic in post #2 is right; the assumption feeding it is the part to check.

Session format: read the paper before posting. The discussion is much better when everyone has. Start with the estimand and population, then methods, then results, then limitations. That order makes critique coherent.

Marking my uncertainty on SURMOUNT-1 explicitly. I am confident about the direction, much less confident about the size, and not confident at all that it generalises past the case in the first post.

Agreed on all of that, and I have nothing to add to it.

Narrowing post #6, because the general version has more than one answer.

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.

Happy to expand any of that if it is the useful part.

Everything in post #8 holds. The case it does not cover is the one I have.

Reading back through the SURMOUNT-1 threads from last year, the same three questions come up every time and only one of them has ever been answered properly. That seems like a documentation gap rather than a knowledge gap.

The failure mode on SURMOUNT-1 is boring rather than dramatic. It is almost always the step everyone assumes was done correctly because it is too simple to get wrong.

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.

Second-hand, so weight it accordingly.

Agreed, and I will stop repeating the version of this I had been repeating.

Picking up post #11: that is the part I would want checked first.

Practical answer on SURMOUNT-1, since the theoretical one is upthread: do the simplest check first, write down the result, and only then decide whether the complicated explanation is needed. It usually is not.