Multiplicity and multiple comparisons: if a trial tests many hypotheses, the chance of a false positive on at least one by random chance increases. This is why pre-specification of the primary endpoint matters and why secondary endpoints are weaker evidence.
Topic summary
[2026 update] How to read a forest plot, properly, from scratch
This is a generated summary. It shows the 8 most-liked posts from a topic of 54, in their original order, with the accepted answer included where one exists. It is a reading aid and it will miss nuance — the full topic is the record.
post #8 answers the question as asked. The question underneath it is different.
The estimand: what the trial set out to estimate. Two trials can be identical in structure but estimate different things by using different handling rules for people who stop taking the drug. Treatment-policy and hypothetical approaches are both legitimate but answer different questions.
20 likes 20mo
an.zamora, post #1: How to read a forest plot, properly, from scratch — that is the question, and I have not found it answered plainly anywhere I have looked. 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… Go to post
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.
m.rasmussen, post #14: post #13 answers the question as asked. The question underneath it is different. 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. Go to post
This follows post #13 rather than contradicting it.
Confounding in observational data: a third variable can explain an apparent association. In a randomised trial, randomisation balances unknown confounders. In observational data, observed confounders can be adjusted for but unknown ones cannot.
n.laurent, post #18: Intent-to-treat versus per-protocol: ITT includes everyone assigned regardless of whether they took the drug. Per-protocol includes only those who completed it as intended. The two can give substantially different results. Go to post
Intent-to-treat versus per-protocol: ITT includes everyone assigned regardless of whether they took the drug. Per-protocol includes only those who completed it as intended. The two can give substantially different results.
m.mwangi, post #26: I read post #24 twice before replying, because I had assumed the opposite. Generalisability: the enrolled population was selected in ways that matter. Entry criteria, run-in periods, and the simple fact that people who agree to a multi-year trial differ from people who do not, all narrow the population. That is how internal validity is… Go to post
Dropout is information: high dropout rates can indicate tolerability problems or lower efficacy than the summary suggests. Where the analysis handled dropouts matters. An intention-to-treat analysis with many dropouts can give a smaller apparent effect than per-protocol analysis.
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.
25 likes 19mo
Coming back to post #42, because the follow-up matters more than the original answer.
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.
29 likes 19mo
Read the full topic (54 posts)
Promoted into the documentation commons. The content of this topic is maintained at STEP-HFpEF — trial digest, with named maintainers and a review date. The promotion was discussed in doc review. Corrections are best raised against the document, which is the version that gets kept current.
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