Topic summary

Revisiting: Primary endpoint hierarchies and why order matters

Evidence › Trials estimand surrogate endpoints discontinuation & dropout intention to treat open label

This is a generated summary. It shows the 5 most-liked posts from a topic of 26, 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.

a.hartmannTL23 May 2026#1

Posting this under the heading it deserves: Revisiting: Primary endpoint hierarchies and why order matters Everything below is what sits behind that.

I was wrong about Primary endpoint hierarchies in a thread last spring and I would like to correct it publicly rather than quietly.

The error was in the units, which changed the conclusion by an order of magnitude. Setting out the corrected version, and the way I now check for that class of mistake.

43 likes 3mo

v.salgadoTL26 May 2026 · edited#6

a.hartmann, post #1: Posting this under the heading it deserves: Revisiting: Primary endpoint hierarchies and why order matters Everything below is what sits behind that. I was wrong about Primary endpoint hierarchies in a thread last spring and I would like to correct it publicly rather than quietly. The error was in the units, which changed the conclusion… Go to post

Where I part company with post #3, and it is a narrow parting.

A treatment-policy estimand asks what happens to people assigned to a strategy, including those who abandon it. A hypothetical estimand asks what would have happened had everyone continued. Both are legitimate and they give different numbers.

I would be interested in a counterexample if anyone has one.

32 likes in reply to #1 3mo

a.stephanopoulosTL3Regular7 May 2026#10

Worth separating two things that post #6 runs together.

Pre-specification is the property that makes a primary endpoint trustworthy. An endpoint chosen after seeing the data can be the best endpoint in the world and it no longer carries the same guarantee.

Marking that as an opinion rather than a finding.

24 likes 3mo

y.adebayoTL28 May 2026#12

I read the earlier replies on Primary endpoint hierarchies twice before writing this, because I had assumed the opposite and wanted to be sure I was disagreeing with what was said rather than what I expected.

32 likes 3mo

SHermansenTL2Member11 May 2026#21

Adding a small correction to the Primary endpoint hierarchies summary above rather than a disagreement with it. The substance holds; one of the figures is out by a factor that matters.

29 likes 3mo

Read the full topic (26 posts)

Promoted into the documentation commons. The content of this topic is maintained at PIONEER 6 — 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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