Journal club: indirect comparison between two programmes, defended and attacked — one year on

The question underneath indirect comparison is usually "how would I tell?" rather than "what is true?", and that one has a method attached to it.

Write down what you would expect to see under each hypothesis before you collect anything. If they predict the same observation, collecting it will not help.

Picking up post #13: that is the part I would want checked first.

Bringing the previous paper on the same question makes the session much better and doubles the preparation. Worth doing every third session rather than every one.

I would put moderate confidence on the mainstream reading of indirect comparison and no more. That is not scepticism for its own sake; it is where the sourcing actually stops.

Post #18 describes the usual case. This is about the unusual one.

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

That is all I can say without guessing.

Seconded. It reads as careful rather than confident, which is the right register.

Reading rather than contributing, but this is the most useful thread I have found on it.

Indirect comparison is one of those subjects where the general answer and the answer for a specific case diverge, and the thread will go in circles until someone says which one is being asked for.

Post #22 answers the question as asked. The question underneath it is different.

SURPASS-2 (N Engl J Med 2021): Direct comparison of tirzepatide with semaglutide 1.0 mg. The 1.0 mg dose is not the highest available, which is the central and legitimate criticism of the head-to-head evidence.

I have changed my mind on this once already, so take it as current rather than settled.

I read post #22 twice before replying, because I had assumed the opposite.

Critical appraisal template: (1) What did the trial set out to estimate? (2) Could the design answer that question? (3) Was the population sufficiently similar to your population to apply the results? (4) What was the absolute effect, not just the relative one? (5) What are the two strongest criticisms available?

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.

Take the reasoning and check the arithmetic; I do not always get it right.

On post #24 — agreed on the reasoning, with one qualification.

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 honest answer is that it depends, and here is what it depends on.

Post #26 is right about the mechanism and I think understates the practical bit.

A request rather than an answer: could whoever has the primary source for indirect comparison post it? I have seen the claim three times this month and each version had lost a qualifier.

I keep a log for indirect comparison specifically because my memory of it turned out to be systematically wrong in one direction. Six weeks of notes cost nothing and settled it.

Building on post #26 rather than restating it.

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.

Post #28 put the caveat in the right place and I want to underline it.

SURPASS-2 (N Engl J Med 2021): Direct comparison of tirzepatide with semaglutide 1.0 mg. The 1.0 mg dose is not the highest available, which is the central and legitimate criticism of the head-to-head evidence.