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What did the placebo arm of SURMOUNT-5 report for reflux?

Asked 27 Aug 2024Modified 19 months agoViewed 15k times
5

Setup, so nobody has to ask: SURMOUNT-5 · reflux.

I would like help reading this properly rather than being told what conclusion to reach.

I have the full report including the method section, so I can quote specifics if that helps.

What can I legitimately conclude from this figure?

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clinical-trials

Reading the primary literature properly: estimands, intention-to-treat versus per-protocol, confidence intervals, absolute versus relative…

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gi-side-effects
gi-side-effects

The gastrointestinal cluster as a whole - nausea, vomiting, diarrhoea, constipation, reflux, early satiety - with trial incidence rates, dropout…

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askedpierce_count24k3827 Aug 2024

5 Answers

Accepted answer first, then by votes
8

Accepted answer

The SURMOUNT-5 placebo arm is the only thing that makes its treatment arm interpretable, and it is the row nobody quotes. Symptoms reported under placebo in these programmes are not rare, because the population is being asked about them weekly and would have had some of them regardless. The attributable figure is the treated rate minus the placebo rate, and that difference is routinely a fraction of the headline. Two cautions on the subtraction: the arms must have been assessed the same way, and a discontinuation for an event removes that participant from later time points in both arms, which flatters whichever arm loses more people.

The short version: the effect is real, the magnitude depends on the population, and the population is usually the part that gets dropped when a result is quoted second-hand.

Placebo arms in this class are not nothing. Lifestyle-intervention placebo arms in the major obesity trials commonly lose two to three per cent of body weight, so an active-arm figure quoted without its comparator overstates the drug effect by roughly that much.

Non-inferiority and superiority designs are not interchangeable. A non-inferiority result says the new agent is not meaningfully worse against a pre-specified margin — it does not say it is as good, and it certainly does not say it is better.

Where a result is quoted from a conference abstract rather than a peer-reviewed publication, the numbers routinely move between the two. It is worth checking which one you are reading.

I am not a clinician and this is not medical advice; it is a reading of a published protocol.

The short version: check the endpoint, check the comparator, check who was excluded, then look at the number.

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DV
answered · acceptedDr_Ilse_Vandenberg113k24829 Aug 2024
Absolute risk reduction rather than relative would make this much more useful. – forty_units 6 months ago
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7

Before comparing two trials, check whether they share an endpoint definition. Frequently they do not, and the numbers then are not comparable in any sense.

Intention-to-treat and per-protocol analyses answer different questions. ITT asks what happens if you offer the treatment; per-protocol asks what happens if it is taken as directed. The gap between the two is a measure of how tolerable the protocol was.

Open-label extensions are not the same evidence as the randomised phase. Once everyone knows what they are taking, the reported outcomes acquire a bias that no analysis fully removes.

If a claim cannot be traced to a named trial with a named endpoint, treat it as a claim rather than as evidence.

edited 19 Dec 2024 by Dr_Hanne_Solberg — expanded the table to cover the lower concentration

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DS
answeredDr_Hanne_Solberg36k2716 Dec 2024
3Is the open-label extension included in that figure, or just the randomised phase? – Dr_Nadia_Farsi 9 months ago
4Which population was that figure from? It moves a lot between the trials. – zeynep_arslan 36 days ago
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5

More usefully, the trial answers a narrower question than the headline suggests, and the narrowing is where the useful information is.

Confidence intervals matter more than point estimates when two trials disagree. Two studies reporting fifteen and twenty per cent whose intervals overlap heavily have not disagreed about anything.

Trial populations are selected. Exclusion criteria in this class routinely remove people with significant renal impairment, prior pancreatitis and unstable psychiatric illness, which is exactly the population the results are then quoted for.

Registry entries at ClinicalTrials.gov carry the pre-specified primary endpoint with a timestamp, which is the cheapest available check on whether an endpoint was changed after the data were seen.

The caveat is that trial evidence is about licensed product administered under supervision. None of it transfers automatically to research-grade material of unverified content.

Quote the interval alongside the estimate and half the disagreements on this site would not start.

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C3
answeredcharge_state_316k389 Sept 2024
4

Answer first: read the primary endpoint, the comparator and the population before you read the effect size. Almost every argument on this site about a trial is really an argument about one of those three.

A composite endpoint is only as informative as its least serious component. Where a cardiovascular composite combines death, infarction and stroke, ask which component moved, because they are not interchangeable outcomes.

Read the protocol and the statistical analysis plan if the result matters to you. Both are usually published alongside.

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DV
answeredDr_Bram_Verhoeven84k24821 Sept 2024
-3

The honest answer here is that the published evidence supports part of the claim and is silent on the rest, and it is worth being precise about which part is which.

Duration decides what can be seen. A 68-week trial can measure weight and glycaemia; it cannot measure anything whose event rate is one per cent per year without enrolling tens of thousands.

Meta-analyses in this area are dominated by whichever trial contributed the most participants, so read the forest plot rather than the summary estimate.

When two sources disagree, the answer is almost always in the methods section of the one you have not read.

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DF
answeredDr_Nadia_Farsi104k2472 Oct 2024
4Thank you for separating the surrogate from the outcome. That distinction gets lost constantly. – Dr_Otto_Lindqvist 5 months ago
3Do you have a reference for the last claim? Not disputing it, just want to read it. – kelvin_lam 4 months ago
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Your answer

Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.

Not medical advice. Research-use-only compounds are not approved for human use.