Topic summary

Non-inferiority margins: how they are chosen and how they are abused — a second dataset

Evidence › Trials randomised trial discontinuation & dropout intention to treat estimand

This is a generated summary. It shows the 5 most-liked posts from a topic of 38, in their original order, with the accepted answer included where one exists. It is a reading aid and it will miss nuance — the full topic is the record.

j.ivaturiTL2 Moderator2 Jan 2026#2

Confounding in observational data: a third variable can explain an apparent association. In a randomised trial, randomisation balances unknown confounders. In observational data, observed confounders can be adjusted for but unknown ones cannot.

31 likes 7mo

y.eriksenTL2 Moderator11 Jan 2026#6

revision_history, post #3: Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing. The correction was fair and I had been repeating something I had not checked carefully enough. Go to post

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

23 likes in reply to #3 7mo

j.vandermolenTL3Regular15 Feb 2026#30

desiccant_notes, post #26: Multiplicity and multiple comparisons: if a trial tests many hypotheses, the chance of a false positive on at least one by random chance increases. This is why pre-specification of the primary endpoint matters and why secondary endpoints are weaker evidence. Go to post

Picking up post #27: that is the part I would want checked first.

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

20 likes in reply to #26 5mo

j.petrovTL2 Moderator19 Feb 2026#33

PSundberg, post #5: I read post #3 twice before replying, because I had assumed the opposite. Multiplicity and multiple comparisons: if a trial tests many hypotheses, the chance of a false positive on at least one by random chance increases. This is why pre-specification of the primary endpoint matters and why secondary endpoints are weaker evidence. Go to post

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

28 likes in reply to #5 5mo

id.almeidaTL2 Moderator24 Feb 2026 · edited#37

Surrogate endpoints: an endpoint that is not the outcome that matters but is measured as a stand-in. HbA1c is a surrogate for long-term glucose control and the short-term complications it prevents. Weight loss is a surrogate for metabolic health and long-term outcomes. Surrogates are useful but not identical to the endpoint that matters.

21 likes 5mo

Read the full topic (38 posts)

Promoted into the documentation commons. The content of this topic is maintained at SURPASS-4 — trial digest, with named maintainers and a review date. The promotion was discussed in doc review. Corrections are best raised against the document, which is the version that gets kept current.

Suggested topics

Topic	Participants	Replies	Views	Activity
Comparators chosen for regulatory reasons rather than clinical ones Evidence › Trials surrogate endpoints open label estimand randomised trial Pinned Closed 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…		2	27k	14mo
Run-in periods and the population they select Evidence › Trials surrogate endpoints discontinuation & dropout estimand randomised trial On the subject in the title: Run-in periods and the population they select Working notes rather than a conclusion. Session topic: PIONEER 6 ( N Engl J Med , 2019). Please read it before posting; the…	+130	142	7.3k	1mo
Follow-up: Open-label extensions: what survives and what does not Evidence › Trials open label intention to treat surrogate endpoints estimand Solved 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…	+22	26	397	16mo
Second pass at: Reading a trial's population section before its results Evidence › Trials open label intention to treat estimand surrogate endpoints Solved Second pass at: Reading a trial's population section before its results Writing it up because I had to work it out twice and would rather nobody else did. I have seen STEP 1 ( N Engl J Med , 2021) cited in…		4	9.5k	10h
Interim analyses and stopping rules Evidence › Trials intention to treat surrogate endpoints open label discontinuation & dropout Interim analyses and stopping rules Writing it up because I had to work it out twice and would rather nobody else did. I have seen SUSTAIN 6 ( N Engl J Med , 2016) cited in support of a claim I do not think…	+25	29	35k	16d

Related topics — sharing the tags randomised trial, discontinuation & dropout, intention to treat

Topic	Participants	Replies	Views	Activity
Coming back to: What the published dose-response for semaglutide actually looks like above 2.4 mg Compounds › Semaglutide effect size type 2 diabetes semaglutide STEP programme Solved The question in the title: What the published dose-response for semaglutide actually looks like above 2.4 mg I will give what I have already checked below so nobody repeats it. I have seen LEADER ( N Engl J…	+23	27	9.9k	1mo
Reading SURMOUNT-1 without the press release Compounds › Tirzepatide SURMOUNT programme effect size randomised trial SURPASS programme Posting this under the heading it deserves: Reading SURMOUNT-1 without the press release Everything below is what sits behind that. I have seen SURMOUNT-4 ( JAMA , 2024) cited in support of a claim I do not…	+103	121	7k	7mo
Subgroup analyses: pre-specified versus discovered — a second dataset Evidence › Trials open label discontinuation & dropout estimand randomised trial On the subject in the title: Subgroup analyses: pre-specified versus discovered — a second dataset Working notes rather than a conclusion. Comparing SURMOUNT-1 ( N Engl J Med , 2022) with SURPASS-4 ( Lancet ,…	+71	79	906	3mo
Coming back to: The SOUL trial and oral semaglutide cardiovascular outcomes Compounds › Oral incretins randomised trial SOUL trial oral semaglutide orforglipron Solved The SOUL trial and oral semaglutide cardiovascular outcomes — setting out what I have, and where I think it stops being reliable. I have seen LEADER ( N Engl J Med , 2016) cited in support of a claim I do not…	+100	104	4.2k	5mo
Revisiting: Primary endpoint hierarchies and why order matters Evidence › Trials estimand surrogate endpoints discontinuation & dropout intention to treat Posting this under the heading it deserves: Revisiting: Primary endpoint hierarchies and why order matters Everything below is what sits behind that. Comparing SURMOUNT-4 ( JAMA , 2024) with SURPASS-2 ( N…	+21	25	46k	3mo