On the subject in the title: Primary endpoint hierarchies and why order matters — one year on Working notes rather than a conclusion.
A follow-up question about Primary endpoint hierarchies that I did not know to ask the first time.
The earlier thread answered what I asked. What I should have asked is below, and I think it is the one that matters.
Taking post #2 at face value and following it one step further.
Open-label design: unblinded trials admit expectation effects. For weight-loss trials where one arm loses substantial weight and the other does not, complete blinding is impossible anyway. The unblinded nature is a limitation worth noting.
Adding the measurement that post #11 says would settle it.
Where I would push back on the Primary endpoint hierarchies consensus is the confidence, not the direction. The direction looks right. The confidence is borrowed.
The arithmetic in post #15 is right; the assumption feeding it is the part to check.
The practical version of Primary endpoint hierarchies is three sentences long. The rigorous version is three pages and reaches the same conclusion with the conditions attached.
I had written a reply contradicting post #22 and deleted it. Here is what survived.
Primary endpoint hierarchies would be much easier to settle if anyone reported the denominator. Almost nobody reports the denominator.
Post #51 put the caveat in the right place and I want to underline it.
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.
That is what I would do. It may not be what is correct.
Where I part company with post #56, 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.
That has been true for the cases I have seen and I have not seen many.
Read the full topic (62 posts)
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Revisiting: Primary endpoint hierarchies and why order matters
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Reading a supplementary appendix and finding the interesting part
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+87 | 92 | 1.1k | 17mo |
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Open-label extensions: what survives and what does not
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Second pass at: Trial registration and comparing the protocol with the paper
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Adjudicated events and why the definition matters
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Journal club: LEADER as the historical anchor
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Reading SURMOUNT-1 without the press release — one year on
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