Journal club: how we handle discontinuation in obesity trials — what changed since

Journal club: how we handle discontinuation in obesity trials — what changed since — setting out what I have, and where I think it stops being reliable.

Session topic: STEP 4 (JAMA, 2021). 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.

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.

This has been discussed before and I could not find the thread, so, again.

The arithmetic in post #3 is right; the assumption feeding it is the part to check.

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.

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

I have left out the parts I could not verify.

Adding thanks rather than a view. I do not have a view worth the space.

Everything in post #3 holds. The case it does not cover is the one I have.

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.

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.

Second-hand, so weight it accordingly.

I had written a reply contradicting post #7 and deleted it. Here is what survived.

Where the group cannot agree, record the disagreement rather than resolving it by seniority. The recorded disagreement is more honest and more useful later.

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.

The arithmetic in post #8 is right; the assumption feeding it is the part to check.

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

Nothing above should be read as advice about what anyone else should do.

Following, with nothing to contribute beyond having asked the same thing elsewhere.

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.

That distinction has done more work for me than anything else in this category.

SURMOUNT-OSA (N Engl J Med 2024): Tirzepatide in obstructive sleep apnoea, using an objective physiological endpoint. Notable because soft endpoints are avoided. Two parallel trials addressed the confounder directly.