Journal club: STEP 1 and the treatment-policy estimand

Journal club: STEP 1 and the treatment-policy estimand Writing it up because I had to work it out twice and would rather nobody else did.

Session topic: STEP 1 (N Engl J Med, 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.

A methods point on STEP 1 rather than a substantive one: if the comparison is not like for like, the difference you are measuring is the difference in method.

Worth separating two things that the opening post runs together.

STEP 1 (N Engl J Med 2021): The pivotal obesity trial for semaglutide and the reference point for most subsequent comparison. Mean weight reduction was substantially larger than anything previously achieved pharmacologically.

The mechanism is plausible, which is not the same as established.

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.