Selection into a registry and what it does to the estimate — a second dataset

Posting this under the heading it deserves: Selection into a registry and what it does to the estimate — a second dataset Everything below is what sits behind that.

Session topic: SURMOUNT-4 (JAMA, 2024). Please read it before posting; the discussion is much better when everyone has.

The question I would like us to start with is what the trial set out to estimate, rather than what it found. Once that is on the table we can talk about whether the design could have answered it, and only then about the numbers.

Specific things I would like covered: the population and how far it generalises, how discontinuation was handled, whether the comparator was a fair one, and what the absolute rather than relative effect looks like.

I will summarise at the end and the summary will feed the relevant digest page.

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

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.

Coming back to post #2, because the follow-up matters more than the original answer.

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.

post #4 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.

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.

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.

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.

On post #6 — agreed on the reasoning, with one qualification.

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.

Coming back to post #9, because the follow-up matters more than the original answer.

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.

Picking up post #9: that is the part I would want checked first.

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.

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.

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.