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Follow-up: Open-label extensions: what survives and what does not

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

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Solved by Isaksen in post #8

Absolute and relative effects answer different questions. Write down the event rate in each arm and the difference between them; everything quotable is derived from those two numbers. Genuinely open to being wrong about this one.

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mi.almeidaTL221 Feb 2025#1

Open-label extensions: what survives and what does not — setting out what I have, and where I think it stops being reliable.

I have spent a fortnight trying to pin Open-label extensions down and I want to set out where I have got to, because I suspect the honest answer is duller than the thread this will produce.

What I have: a consistent observation across a small number of cases, collected the same way each time. What I do not have: any controlled comparison, or any reason to think my cases are representative.

The specific question is whether the pattern survives once the obvious confounder is removed. I cannot remove it with what I have.

4 likes 17mo

TavaresTL1Member24 Feb 2025#2

Reporting rather than recommending, on Open-label extensions. What happened is above. Whether it should have is a different question and not one I am qualified to answer.

0 likes 17mo

p.boatengTL227 Feb 2025#3

The opening post and I disagree about the size of the effect, not about the direction.

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.

26 likes 17mo

l.chevalierTL3Regular1 Mar 2025#4

mi.almeida, post #1: Open-label extensions: what survives and what does not — setting out what I have, and where I think it stops being reliable. I have spent a fortnight trying to pin Open-label extensions down and I want to set out where I have got to, because I suspect the honest answer is duller than the thread this will produce. What I have: a… Go to post

That is a fair summary of where the discussion has got to.

12 likes in reply to #1 17mo

m.adebayoTL23 Mar 2025#5

The most useful reply I ever got about Open-label extensions was a request to state my units. It sounds like pedantry and it has saved me twice.

4 likes 17mo

bench_peakTL3Regular5 Mar 2025#6

Post #3 is right about the mechanism and I think understates the practical bit.

Since Open-label extensions keeps coming up, it should probably be a maintained page rather than a recurring thread. I am happy to draft it if someone with more direct experience will review it.

0 likes 17mo

t.batistaTL27 Mar 2025#7

Tavares, post #2: Reporting rather than recommending, on Open-label extensions. What happened is above. Whether it should have is a different question and not one I am qualified to answer. Go to post

Worth separating two things that post #3 runs together.

Risk of bias: structured appraisal of internal validity. Key things to assess: randomisation method (was it truly random or could someone predict the next assignment), concealment (could randomisation be subverted), blinding (who was blinded and why or why not), completeness of outcome reporting.

0 likes in reply to #2 17mo

IsaksenTL3Regular Solution9 Mar 2025#8

Absolute and relative effects answer different questions. Write down the event rate in each arm and the difference between them; everything quotable is derived from those two numbers.

Genuinely open to being wrong about this one.

18 likes in reply to #1 17mo

t.ibarraTL210 Mar 2025#9

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

I had written a reply contradicting post #7 and deleted it. Here is what survived.

One more thing on Open-label extensions that took me far too long to see: the two figures people quote are not measuring the same quantity. Once you notice that, the apparent contradiction disappears.

t.nardoneTL3Regular12 Mar 2025 · edited#10

Confirming post #7 from a second method, which matters more than confirming it from a second person.

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.

The number is defensible. The precision I gave it is not.

27 likes 17mo

s.leclercTL4 Moderator14 Mar 2025#11

p.boateng, post #3: The opening post and I disagree about the size of the effect, not about the direction. 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. Go to post

The arithmetic in post #8 is right; the assumption feeding it is the part to check.

The version of Open-label extensions that I was taught turned out to be a teaching simplification. Useful, and not true in the way I had assumed it was.

15 likes in reply to #3 16mo

n.silvaTL215 Mar 2025#12

30 likes 16mo

a.reyesTL4 Admin17 Mar 2025#13

On Open-label extensions, I would rather understate and be corrected upward than overstate and be quoted. That is a house style here and it is a good one.

0 likes 16mo

l.salinasTL219 Mar 2025 · edited#14

Whatever the answer on Open-label extensions turns out to be, the method for getting there is the same: state the assumption, do the arithmetic in public, invite the correction.

3 likes 16mo

dr.villanuevaTL3Physician20 Mar 2025#15

Narrowing post #12, because the general version has more than one answer.

Absolute and relative effects answer different questions. Write down the event rate in each arm and the difference between them; everything quotable is derived from those two numbers.

I would hold that lightly until someone with a larger sample weighs in.

21 likes in reply to #3 16mo

ch.correiaTL222 Mar 2025#16

Everything in post #14 holds. The case it does not cover is the one I have.

What I want from this Open-label extensions thread is the list of things that would need to be true for the claim to hold. If we can write that list, we can check it.

0 likes 16mo

ms_hollowayTL4Mass spectrometrist23 Mar 2025#17

I have been on both sides of the Open-label extensions argument in this category within eighteen months, which should tell you how strong the evidence for either side is.

1 like 16mo

e.iyerTL225 Mar 2025#18

ms_holloway, post #17: I have been on both sides of the Open-label extensions argument in this category within eighteen months, which should tell you how strong the evidence for either side is. Go to post

This is the sort of thing that ought to be settled and apparently is not.

6 likes in reply to #17 16mo

b.vestergaardTL226 Mar 2025#19

t.ibarra, post #9: I had written a reply contradicting post #7 and deleted it. Here is what survived. One more thing on Open-label extensions that took me far too long to see: the two figures people quote are not measuring the same quantity. Once you notice that, the apparent contradiction disappears. Go to post

A definition problem is doing most of the work in this Open-label extensions discussion. Once the term is pinned down I suspect the disagreement mostly goes away and what is left is small.

6 likes in reply to #9 16mo

m.coelhoTL227 Mar 2025#20

What I would check first on Open-label extensions is whether the thing being measured moved or whether the way of measuring it moved. Those look identical in a graph.

16 likes 16mo

r.torrenceTL2Member29 Mar 2025 · edited#21

Everything in post #19 holds. The case it does not cover is the one I have.

23 likes 16mo

c.kuuselaTL230 Mar 2025#22

Bookmarking this. I will come back when I have something worth adding.

10 likes 16mo

taper_fileTL3Regular1 Apr 2025#23

r.torrence, post #21: Everything in post #19 holds. The case it does not cover is the one I have. 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. Go to post

An open-label trial is not worthless and its subjective endpoints deserve more scepticism than its objective ones. That is a graded judgement rather than a verdict.

That is one dataset and I would not build a rule on it.

1 like in reply to #21 16mo

m.yildizTL22 Apr 2025#24

Building on post #23 rather than restating it.

The most useful thing anyone has posted about Open-label extensions in this category was a table of what had been measured and by whom. That is what I would want again.

0 likes 16mo

lyophil_marginTL3Regular3 Apr 2025#25

I read post #23 twice before replying, because I had assumed the opposite.

Open-label extensions has been discussed here with more heat than it deserves, mostly because two definitions have been in play the whole time.

16 likes 16mo

e.kuipersTL25 Apr 2025#26

Post #23 answers the question as asked. The question underneath it is different.

Absolute and relative effects answer different questions. Write down the event rate in each arm and the difference between them; everything quotable is derived from those two numbers.

6 likes in reply to #2 16mo

NorringtonTL3Regular6 Apr 2025#27

c.kuusela, post #22: Bookmarking this. I will come back when I have something worth adding. Go to post

Where the Open-label extensions reasoning breaks down for me is the step from the group result to the individual case. That step is almost never argued for.

0 likes in reply to #22 16mo

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Follow-up: Open-label extensions: what survives and what does not

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