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Non-inferiority margins: how they are chosen and how they are abused — a second dataset — setting out what I have, and where I think it stops being reliable. Comparing FLOW ( N Engl J Med , 2024) with…

On the subject in the title: Reading a supplementary appendix and finding the interesting part Working notes rather than a conclusion. Comparing SELECT ( N Engl J Med , 2023) with FLOW ( N Engl J Med , 2024)…

Posting this under the heading it deserves: Non-inferiority margins: how they are chosen and how they are abused Everything below is what sits behind that. Comparing SURPASS-2 ( N Engl J Med , 2021) with…

Journal club: semaglutide in MASH, and surrogate endpoints — does this still hold? I have a specific reason for asking rather than idle curiosity, and the context is below. Comparing STEP 1 ( N Engl J Med ,…

The question in the title: How to read a forest plot, properly, from scratch I will give what I have already checked below so nobody repeats it. Session topic: STEP 4 ( JAMA , 2021). Please read it before…

Journal club: the retatrutide phase 2 obesity paper — setting out what I have, and where I think it stops being reliable. I have seen FLOW ( N Engl J Med , 2024) cited in support of a claim I do not think it…

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…

Second pass at: Journal club: STEP 4 and what a withdrawal design can prove Writing it up because I had to work it out twice and would rather nobody else did. Session topic: SURMOUNT-OSA ( N Engl J Med ,…

Posting this under the heading it deserves: Journal club: indirect comparison between two programmes, defended and attacked — one year on Everything below is what sits behind that. Comparing SURPASS-2 ( N…

On the subject in the title: Journal club: STEP-HFpEF and symptom endpoints — a second dataset Working notes rather than a conclusion. Comparing SELECT ( N Engl J Med , 2023) with STEP 4 ( JAMA , 2021) and…

Posting this under the heading it deserves: Journal club: orforglipron phase 2 and the non-peptide question Everything below is what sits behind that. Session topic: SURMOUNT-4 ( JAMA , 2024). Please read it…

On the subject in the title: Sample size calculations, read backwards from the published number Working notes rather than a conclusion. Session topic: PIONEER 6 ( N Engl J Med , 2019). Please read it before…

Journal club: STEP-HFpEF and symptom endpoints — setting out what I have, and where I think it stops being reliable. Comparing SURMOUNT-2 ( Lancet , 2023) with SURMOUNT-1 ( N Engl J Med , 2022) and finding…

Comparators chosen for regulatory reasons rather than clinical ones — one year on — setting out what I have, and where I think it stops being reliable. Session topic: SURMOUNT-2 ( Lancet , 2023). Please read…

Journal club: STEP 8 and the fairness of the comparator dose — setting out what I have, and where I think it stops being reliable. Comparing SURMOUNT-2 ( Lancet , 2023) with STEP 8 ( JAMA , 2022) and finding…

Individual randomised trials: design, population, endpoints, results, and limitations. This post is a community wiki: any member at trust level 3 or above can edit it, and every edit is recorded with its…

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

Journal club: the CagriSema phase 2 combination paper — a second dataset — setting out what I have, and where I think it stops being reliable. I have seen FLOW ( N Engl J Med , 2024) cited in support of a…

Posting this under the heading it deserves: Journal club: SURMOUNT-4 and continuation versus withdrawal — a second dataset Everything below is what sits behind that. Comparing STEP 8 ( JAMA , 2022) with FLOW…

Interim analyses and stopping rules — does this still hold? — that is the question, and I have not found it answered plainly anywhere I have looked. Comparing SCALE ( N Engl J Med , 2015) with SURMOUNT-4 (…

Posting this under the heading it deserves: Second pass at: Trial registration and comparing the protocol with the paper Everything below is what sits behind that. I have seen SCALE ( N Engl J Med , 2015)…

On the subject in the title: Comparators chosen for regulatory reasons rather than clinical ones Working notes rather than a conclusion. Session topic: SURMOUNT-1 ( N Engl J Med , 2022). Please read it before…

Adjudicated events and why the definition matters — the long version Writing it up because I had to work it out twice and would rather nobody else did. Comparing SURPASS-4 ( Lancet , 2021) with STEP 4 ( JAMA…

Journal club: STEP 4 and what a withdrawal design can prove — one year on Writing it up because I had to work it out twice and would rather nobody else did. Session topic: SURMOUNT-OSA ( N Engl J Med , 2024).…

On the subject in the title: Journal club: the retatrutide phase 2 obesity paper Working notes rather than a conclusion. I have seen SURMOUNT-1 ( N Engl J Med , 2022) cited in support of a claim I do not…

Open-label extensions: what survives and what does not — setting out what I have, and where I think it stops being reliable. Comparing SURMOUNT-2 ( Lancet , 2023) with SURMOUNT-1 ( N Engl J Med , 2022) and…

The question in the title: Journal club: SUSTAIN 6 and its retinopathy signal — does this still hold? I will give what I have already checked below so nobody repeats it. I have seen SURMOUNT-2 ( Lancet ,…

Our recurring session. One named paper per topic, methods first, conclusions last. Everyone reads before posting. This post is a community wiki: any member at trust level 3 or above can edit it, and every…

Posting this under the heading it deserves: Journal club: SURMOUNT-OSA and a hard endpoint in a soft field Everything below is what sits behind that. Comparing SURMOUNT-4 ( JAMA , 2024) with SCALE ( N Engl J…

Journal club: SURPASS-2 and the semaglutide 1 mg comparator Writing it up because I had to work it out twice and would rather nobody else did. Session topic: SURPASS-4 ( Lancet , 2021). Please read it before…