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Evidence · Study critique

A claim built entirely on a subgroup analysis

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Solved by va.baptista in post #9
Worth separating two things that post #5 runs together. Multiple comparisons: if a paper reports many outcomes, the chance of a spurious association by random chance is real. Pre-specification of primary outcomes matters and secondary analyses are weaker evidence.

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AS
a.salcedoTL3Regular20 Apr 2025#1

A claim built entirely on a subgroup analysis Writing it up because I had to work it out twice and would rather nobody else did.

I have seen SUSTAIN 6 (N Engl J Med, 2016) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows.

My reading is that the trial is sound for its own question and is being stretched to answer a different one. I might be wrong about that, which is why this is a topic rather than a correction.

What I would like from this discussion: someone who disagrees with me to say why, with the section of the paper they are relying on.

26 likes 15mo
KH
k.haddadTL2 Moderator22 Apr 2025#2

Defending a paper against criticism: if the authors respond, they might clarify something the paper explained poorly. Their response might also miss your point. Either way, the exchange in public is more useful than quiet disagreement.

5 likes 15mo
MI
m.ivaturiTL2 Moderator23 Apr 2025#3

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

Publication bias: a single published positive trial is weaker evidence than multiple published trials with consistent results. Asking whether there are unpublished negative trials is a fair critical question.

0 likes 15mo
AS
a.silvaTL2 Moderator24 Apr 2025#4

This follows the opening post rather than contradicting it.

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 15mo
NP
n.petrovTL2 Moderator25 Apr 2025#5
k.haddad, post #2: Defending a paper against criticism: if the authors respond, they might clarify something the paper explained poorly. Their response might also miss your point. Either way, the exchange in public is more useful than quiet disagreement. Go to post

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

What makes a methodological criticism substantive: it identifies a specific feature of the design that materially affects what the paper can conclude. "Small sample size" alone is weak. "Small sample size for a rare outcome, so the confidence interval is wide" is stronger.

9 likes in reply to #2 15mo
DB
d.barrosTL2 Moderator25 Apr 2025#6
a.salcedo, post #1: A claim built entirely on a subgroup analysis Writing it up because I had to work it out twice and would rather nobody else did. I have seen SUSTAIN 6 ( N Engl J Med , 2016) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows. My reading is that the trial is… Go to post

Generalisability: do the inclusion/exclusion criteria narrow the population so much that results do not apply to real people asking about it? This is a fair criticism but requires specificity about which real people and why the difference matters.

2 likes in reply to #1 15mo
SD
s.dziedzicTL226 Apr 2025#7
BN
b.nilsenTL2 Moderator27 Apr 2025 · edited#8

Picking up post #5: that is the part I would want checked first.

Criticise the method, not the author: a paper with a weak design is not a bad paper by someone with bad intentions. It is a paper that answers a limited question. Sometimes that is what the sponsor wanted, sometimes the researchers did the best they could with constraints.

21 likes 15mo
VB
va.baptistaTL2 Moderator Solution28 Apr 2025#9

Worth separating two things that post #5 runs together.

Multiple comparisons: if a paper reports many outcomes, the chance of a spurious association by random chance is real. Pre-specification of primary outcomes matters and secondary analyses are weaker evidence.

27 likes 15mo
SC
so.cardosoTL2 Moderator29 Apr 2025#10

post #9 is right about the mechanism and I think understates the practical bit.

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

13 likes 15mo
VK
v.klausenTL3Regular29 Apr 2025 · edited#11

post #10 answers the question as asked. The question underneath it is different.

Choosing the worst interpretation: "The confidence interval includes a harmful effect" is true if the CI goes from -1 to +5. But assuming the worst-case scenario is not how you use the evidence. The point estimate and the precision both matter.

12 likes 15mo
CH
ca.haddadTL2 Moderator30 Apr 2025#12
d.barros, post #6: Generalisability: do the inclusion/exclusion criteria narrow the population so much that results do not apply to real people asking about it? This is a fair criticism but requires specificity about which real people and why the difference matters. Go to post

On post #8 — agreed on the reasoning, with one qualification.

Bias towards the null and bias away from the null: different criticisms have different directions. Differential dropout might bias away from null; conservative statistical analysis might bias toward null.

25 likes in reply to #6 15mo
G
GDashwoodTL3Regular1 May 2025#13

Building consensus on which criticisms matter: if everyone agrees that the sample size is small but only you think that affects the conclusion, maybe your criticism is more idiosyncratic. That does not make it wrong but it is worth noticing.

0 likes 15mo
JT
j.teixeiraTL2 Moderator2 May 2025#14

Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.

The correction was fair and I had been repeating something I had not checked carefully enough.

4 likes 15mo
GI
g.ibarraTL2 Moderator2 May 2025#15

post #14 is right about the mechanism and I think understates the practical bit.

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

7 likes 15mo
SC
s.cardosoTL2 Moderator3 May 2025#16
va.baptista, post #9: Worth separating two things that post #5 runs together. Multiple comparisons: if a paper reports many outcomes, the chance of a spurious association by random chance is real. Pre-specification of primary outcomes matters and secondary analyses are weaker evidence. Go to post

Confounding: in observational data, is there a third variable that explains the apparent association? In randomised data, randomisation should balance unknown confounders, though known confounders can be adjusted for.

18 likes in reply to #9 15mo
BP
b.petrovTL2 Moderator4 May 2025#17
GDashwood, post #13: Building consensus on which criticisms matter: if everyone agrees that the sample size is small but only you think that affects the conclusion, maybe your criticism is more idiosyncratic. That does not make it wrong but it is worth noticing. Go to post

Criticise the method, not the author: a paper with a weak design is not a bad paper by someone with bad intentions. It is a paper that answers a limited question. Sometimes that is what the sponsor wanted, sometimes the researchers did the best they could with constraints.

0 likes in reply to #13 15mo
JN
j.nwosuTL2 Moderator4 May 2025#18

I read post #16 twice before replying, because I had assumed the opposite.

Building consensus on which criticisms matter: if everyone agrees that the sample size is small but only you think that affects the conclusion, maybe your criticism is more idiosyncratic. That does not make it wrong but it is worth noticing.

1 like 15mo
NS
n.stanescuTL2 Moderator5 May 2025#19
va.baptista, post #9: Worth separating two things that post #5 runs together. Multiple comparisons: if a paper reports many outcomes, the chance of a spurious association by random chance is real. Pre-specification of primary outcomes matters and secondary analyses are weaker evidence. Go to post

When you change your mind: if a reply convinces you that your criticism was not well-founded, say so plainly. The critique might still be real but smaller than you originally thought. That is not a failure — it is how discussion works.

24 likes in reply to #9 15mo
NH
n.haddadTL2 Moderator6 May 2025 · edited#20

Choosing the worst interpretation: "The confidence interval includes a harmful effect" is true if the CI goes from -1 to +5. But assuming the worst-case scenario is not how you use the evidence. The point estimate and the precision both matter.

0 likes 15mo
TN
t.ndiayeTL2 Moderator6 May 2025#21
g.ibarra, post #15: post #14 is right about the mechanism and I think understates the practical bit. Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up. Go to post

Bias towards the null and bias away from the null: different criticisms have different directions. Differential dropout might bias away from null; conservative statistical analysis might bias toward null.

17 likes in reply to #15 15mo
SB
s.bergstromTL2 Moderator7 May 2025#22

post #21 is right about the mechanism and I think understates the practical bit.

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.

7 likes 15mo
PM
p.mbekiTL2 Moderator7 May 2025#23

I read post #21 twice before replying, because I had assumed the opposite.

Publication bias: a single published positive trial is weaker evidence than multiple published trials with consistent results. Asking whether there are unpublished negative trials is a fair critical question.

1 like 15mo
AF
a.friskTL2 Moderator8 May 2025#24
s.bergstrom, post #22: post #21 is right about the mechanism and I think understates the practical bit. 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,… Go to post

Defending a paper against criticism: if the authors respond, they might clarify something the paper explained poorly. Their response might also miss your point. Either way, the exchange in public is more useful than quiet disagreement.

0 likes in reply to #22 15mo
JS
j.steinerTL2 Moderator9 May 2025#25

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.

11 likes 15mo
NM
n.moreauTL2 Moderator9 May 2025#26

What makes a methodological criticism substantive: it identifies a specific feature of the design that materially affects what the paper can conclude. "Small sample size" alone is weak. "Small sample size for a rare outcome, so the confidence interval is wide" is stronger.

3 likes 15mo
MB
m.brobergTL2 Moderator10 May 2025 · edited#27

Coming back to post #25, because the follow-up matters more than the original answer.

Generalisability: do the inclusion/exclusion criteria narrow the population so much that results do not apply to real people asking about it? This is a fair criticism but requires specificity about which real people and why the difference matters.

0 likes 15mo
AR
a.reyesTL4 Admin11 May 2025#28
p.mbeki, post #23: I read post #21 twice before replying, because I had assumed the opposite. Publication bias: a single published positive trial is weaker evidence than multiple published trials with consistent results. Asking whether there are unpublished negative trials is a fair critical question. Go to post

Picking up post #25: that is the part I would want checked first.

Confounding: in observational data, is there a third variable that explains the apparent association? In randomised data, randomisation should balance unknown confounders, though known confounders can be adjusted for.

33 likes in reply to #23 15mo
L
LJankowiakTL3Regular11 May 2025#29

Multiple comparisons: if a paper reports many outcomes, the chance of a spurious association by random chance is real. Pre-specification of primary outcomes matters and secondary analyses are weaker evidence.

0 likes 15mo
MA
mi.amankwahTL212 May 2025#30