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Evidence · Journal club · continued

Journal club: STEP 1 and the treatment-policy estimand — does this still hold? posts 31–60

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

SO
s.okaforTL218 Apr 2025#31

A definition problem is doing most of the work in this STEP 1 discussion. Once the term is pinned down I suspect the disagreement mostly goes away and what is left is small.

23 likes 15mo
RA
r.aldana_pharmdTL4Pharmacist18 Apr 2025#32

Sessions on negative or null results are consistently the most instructive and the hardest to get anyone to attend.

The literature is thinner on this than the confidence in the thread implies.

11 likes 15mo
EV
e.vargaTL218 Apr 2025#33
y.mensah, post #19: STEP 1 was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread. Go to post

Post #30 describes the usual case. This is about the unusual one.

What I would check first on STEP 1 is whether the thing being measured moved or whether the way of measuring it moved. Those look identical in a graph.

3 likes in reply to #19 15mo
BN
bench_notesTL4 Moderator18 Apr 2025#34

Sensible. I would want the same detail before I acted on it either.

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a.novakTL218 Apr 2025#35

The most common failure mode is spending fifty minutes on the effect size and ten on the population. Reversing that ratio would improve most sessions.

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a.batistaTL218 Apr 2025#36

Reading this STEP 1 thread as someone who came in with a fixed view: the third and seventh replies moved me and the confident ones did not.

6 likes 15mo
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a.nwosuTL218 Apr 2025 · edited#37
l.chevalier, post #25: Adding the measurement that post #23 says would settle it. Where I would push back on the STEP 1 consensus is the confidence, not the direction. The direction looks right. The confidence is borrowed. Go to post

On post #33 — agreed on the reasoning, with one qualification.

On STEP 1, 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.

1 like in reply to #25 15mo
DT
d.tammTL218 Apr 2025#38

Reading order that works for these sessions: registry entry, methods, baseline table, primary result, then abstract last. Reading the abstract first anchors everything that follows.

Filing this under things that are true until someone shows me otherwise.

0 likes 15mo
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a.zamoraTL219 Apr 2025#39

Right, and stated more narrowly than I would have dared to state it.

0 likes 15mo
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c.silvaTL219 Apr 2025#40
m.dalgaard, post #1: Asking directly, because I could not find a straight answer: Journal club: STEP 1 and the treatment-policy estimand — does this still hold? Working notes on STEP 1 rather than a conclusion. I would rather post the reasoning while it can still be corrected than post the answer once I am committed to it. Everything below is checkable.… Go to post

Post #37 is right about the mechanism and I think understates the practical bit.

Second-hand on STEP 1, so weight it accordingly — someone whose method I trust told me this and I have not verified it myself.

22 likes in reply to #1 15mo
FH
f.haddadTL219 Apr 2025 · edited#41

This follows post #38 rather than contradicting it.

I have no financial interest in anything named in this thread and I want to say so before I comment on STEP 1, because it is the sort of subject where it matters.

0 likes 15mo
ER
eire_readerTL2Regional · IE19 Apr 2025#42

Worth separating two things that post #40 runs together.

STEP 1 (N Engl J Med 2021): The pivotal obesity trial for semaglutide and the reference point for most subsequent comparison. Mean weight reduction was substantially larger than anything previously achieved pharmacologically.

1 like 15mo
MB
m.balogunTL219 Apr 2025#43

The baseline characteristics table is the single most useful page for the questions that get asked here, because it tells you who the result applies to.

9 likes 15mo
PN
p.novotnyTL2Regular19 Apr 2025#44
a.zamora, post #39: Right, and stated more narrowly than I would have dared to state it. Go to post

Adding a reference point for STEP 1. Mine is a single case, collected without controls, and I am posting the method alongside it so it can be discounted appropriately.

21 likes in reply to #39 15mo
RV
r.vukovicTL219 Apr 2025#45

Agreed on STEP 1, with one qualification that I think matters. The reasoning holds for the case as described. Change the starting assumption and it does not, and the starting assumption is the part nobody states.

0 likes 15mo
UC
unit_conversionTL3Regular19 Apr 2025#46

On post #44 — agreed on the reasoning, with one qualification.

Reading order that works for these sessions: registry entry, methods, baseline table, primary result, then abstract last. Reading the abstract first anchors everything that follows.

I would want a second opinion before relying on that.

2 likes 15mo
ES
e.steinerTL219 Apr 2025#47
p.boateng, post #26: Having read the whole STEP 1 thread before replying: the question in the first post has not actually been answered yet, and three of us have answered a nearby one instead. Go to post

Post #46 is right about the mechanism and I think understates the practical bit.

Two people in this thread mean different things by STEP 1 and are disagreeing about the definition while believing they are disagreeing about the facts. Worth pausing to define it.

14 likes in reply to #26 15mo
TP
tracked_parcelTL219 Apr 2025#48
NH
n.hartmannTL219 Apr 2025#49
j.fonseca, post #16: Post #14 is the version of this I will quote in future. One addition. Two sentences on STEP 1 and then I will stop, because the rest is speculation and the thread is better without mine. What is documented is narrow. What is inferred from it is broad. The gap between them is where every argument here lives. Go to post

The reason STEP 1 keeps being re-asked is that the answer is conditional and people quote it without the condition. It is not that the answer is unknown.

0 likes in reply to #16 15mo
VS
vial_slopeTL3Regular19 Apr 2025 · edited#50

Where the group cannot agree, record the disagreement rather than resolving it by seniority. The recorded disagreement is more honest and more useful later.

This is where my knowledge stops and I would rather mark the edge than blur it.

5 likes 15mo
MM
methods_marginTL3Regular19 Apr 2025#51

I changed my mind about STEP 1 after someone here asked me for the source and I could not produce one. That is worth saying out loud because it is the ordinary way it happens.

17 likes 15mo
KB
k.batistaTL219 Apr 2025#52
a.zamora, post #39: Right, and stated more narrowly than I would have dared to state it. Go to post

Session format: read the paper before posting. The discussion is much better when everyone has. Start with the estimand and population, then methods, then results, then limitations. That order makes critique coherent.

7 likes in reply to #39 15mo
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IRenaudinTL2Member19 Apr 2025#53

On STEP 1, the part that usually goes wrong is that the question is asked as though it has one answer. It has a range, and the width of the range is the interesting bit.

If you can post the two or three numbers you are working from, several people here will check the arithmetic rather than argue about the conclusion.

0 likes 15mo
SC
s.chowdhuryTL3Regular19 Apr 2025#54

Narrowing post #51, because the general version has more than one answer.

I would rather this thread reach "we do not know" about STEP 1 than reach a confident answer that nobody can support when asked.

33 likes 15mo
AK
a.kwiatkowskiTL2Member19 Apr 2025#55

STEP 1 (N Engl J Med 2021): The pivotal obesity trial for semaglutide and the reference point for most subsequent comparison. Mean weight reduction was substantially larger than anything previously achieved pharmacologically.

12 likes 15mo
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n.kaufmannTL219 Apr 2025#56
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NardoneTL2Member19 Apr 2025#57
s.okafor, post #31: A definition problem is doing most of the work in this STEP 1 discussion. Once the term is pinned down I suspect the disagreement mostly goes away and what is left is small. Go to post

I read post #55 twice before replying, because I had assumed the opposite.

A note on scope: what I am saying about STEP 1 applies to the case in the first post and I would not extend it further without checking.

0 likes in reply to #31 15mo
MA
m.amankwahTL220 Apr 2025 · edited#58

Post #55 answers the question as asked. The question underneath it is different.

The figures usually contain the finding and the text usually contains the interpretation. Separating them for the first twenty minutes is a discipline worth keeping.

That is the version I use. It may not be the version that is correct.

25 likes 15mo
RM
r.mcalisterTL3Regular20 Apr 2025#59
p.mwangi, post #12: My understanding of STEP 1 is a few years old and may have been superseded. If it has been, I would genuinely like to know rather than keep repeating it. Go to post

This is the answer, and the reason it is the answer is the more useful part.

7 likes in reply to #12 15mo
AI
a.iyerTL220 Apr 2025#60

Confirming post #58 from a second method, which matters more than confirming it from a second person.

The most common failure mode is spending fifty minutes on the effect size and ten on the population. Reversing that ratio would improve most sessions.

The mechanism is plausible, which is not the same as established.

1 like 15mo