Evidence · Trials · continued

Primary endpoint hierarchies and why order matters — one year on posts 61–62

Evidence › Trials surrogate endpoints discontinuation & dropout estimand randomised trial Solved

This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1 · go to the accepted answer.

baseline_peakTL227 Jul 2026#61

Collapsed as off-topic by two members at trust level 3 or above

post #60 is right about the mechanism and I think understates the practical bit.

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.

b.nwosuTL2 Moderator27 Jul 2026#62

Worth separating two things that post #58 runs together.

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.

22 likes 11h

Promoted into the documentation commons. The content of this topic is maintained at Retatrutide phase 2 (type 2 diabetes) — 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
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
Reading a supplementary appendix and finding the interesting part Evidence › Trials open label discontinuation & dropout intention to treat estimand Reading a supplementary appendix and finding the interesting part — 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…	+87	92	1.1k	17mo
Open-label extensions: what survives and what does not Evidence › Trials discontinuation & dropout randomised trial estimand Closed Posting this under the heading it deserves: Open-label extensions: what survives and what does not Everything below is what sits behind that. Comparing STEP 8 ( JAMA , 2022) with PIONEER 6 ( N Engl J Med ,…		4	22k	3mo
Second pass at: Trial registration and comparing the protocol with the paper Evidence › Trials estimand discontinuation & dropout randomised trial open label 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)…	+30	34	33k	13mo
Adjudicated events and why the definition matters Evidence › Trials estimand intention to treat discontinuation & dropout surrogate endpoints Under review On the subject in the title: Adjudicated events and why the definition matters Working notes rather than a conclusion. Session topic: SURMOUNT-1 ( N Engl J Med , 2022). Please read it before posting; the…		2	4.5k	2mo

Related topics — sharing the tags surrogate endpoints, discontinuation & dropout, estimand

Topic	Participants	Replies	Views	Activity
Journal club: LEADER as the historical anchor Evidence › Journal club estimand number needed to treat journal club effect size Pinned Journal club: LEADER as the historical anchor Writing it up because I had to work it out twice and would rather nobody else did. Comparing STEP 1 ( N Engl J Med , 2021) with SURMOUNT-4 ( JAMA , 2024) and…	+103	110	8.1k	2h
Why retatrutide discussion here is more cautious than elsewhere — one year on Compounds › Retatrutide TRIUMPH programme effect size preprint retatrutide Asking directly, because I could not find a straight answer: Why retatrutide discussion here is more cautious than elsewhere — one year on Session topic: PIONEER 6 ( N Engl J Med , 2019). Please read it…	+92	97	3.6k	20h
Coming back to: Amylin analogue mechanism: satiety signalling separate from GLP-1 Compounds › Cagrilintide & amylin analogues cagrisema effect size randomised trial cagrilintide On the subject in the title: Amylin analogue mechanism: satiety signalling separate from GLP-1 Working notes rather than a conclusion. I have seen SELECT ( N Engl J Med , 2023) cited in support of a claim I…	+27	31	671	12mo
Coming back to: Nausea profile of amylin analogues compared with GLP-1 agonists Compounds › Cagrilintide & amylin analogues effect size cagrilintide cagrisema amylin analogues Posting this under the heading it deserves: Nausea profile of amylin analogues compared with GLP-1 agonists Everything below is what sits behind that. Comparing SCALE ( N Engl J Med , 2015) with FLOW ( N Engl…	+48	53	31k	13mo
Reading SURMOUNT-1 without the press release — one year on Compounds › Tirzepatide effect size SURPASS programme randomised trial Solved Closed Reading SURMOUNT-1 without the press release — one year on — 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…	+45	50	7.6k	5mo