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Evidence · Trials · continued

Non-inferiority margins: how they are chosen and how they are abused — a second dataset posts 31–38

This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.

FK
f.kimaniTL2 Moderator16 Feb 2026#31

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.

2 likes 5mo
TV
t.vasquezTL4 Moderator18 Feb 2026#32
i.amankwah, post #29: The estimand: what the trial set out to estimate. Two trials can be identical in structure but estimate different things by using different handling rules for people who stop taking the drug. Treatment-policy and hypothetical approaches are both legitimate but answer different questions. Go to post
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Worth separating two things that post #28 runs together.

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.

9 likes in reply to #29 5mo
JP
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.

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.

28 likes in reply to #5 5mo
CR
compounding_ruthTL4Pharmacist20 Feb 2026#34

Absolute numbers, not just relative: a 30% relative reduction tells you the ratio but not the practical magnitude. The event rate in each arm and the difference between them tells you how many people benefit.

0 likes 5mo
IN
i.norgaardTL221 Feb 2026#35
IT
impurity_tableTL3Analytical chemist23 Feb 2026#36
taper_shift, post #13: 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. Go to post

On post #32 — agreed on the reasoning, with one qualification.

Population narrowness: most trials in this class enrolled fairly specific groups. Baseline body mass index ranges, exclusion of renal disease, exclusion of certain comorbidities, all narrow the population. Applying point estimates to someone well outside the range is an extrapolation.

5 likes in reply to #13 5mo
IA
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
BV
bias_varianceTL4Biostatistician25 Feb 2026#38

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.

0 likes 5mo
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.

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