What did the placebo arm of SUSTAIN-6 report for reflux?

What I am working with: SUSTAIN-6 · reflux.

I have read the primary source rather than the summary, which has left me with more questions.

I understand the headline. I do not understand the footnotes, and the footnotes look important.

What would I need in addition before this supported a decision?

The underlying point is that this is answerable from the published record, but only if you take the placebo arm seriously rather than reading the active arm alone.

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.

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.

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

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

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.

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.

It helps to be literal here: 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.

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

edited 7 Feb 2025 by sunniva_dahl — fixed an arithmetic slip in the third paragraph

Look at the discontinuation rate alongside the efficacy figure. A large effect in the two thirds who stayed is a different result from a large effect in everyone.

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.

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

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.

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.

One qualification: absence of a signal in a trial of this size is not evidence of absence for a rare event. It is evidence that the event is rarer than the trial could detect.

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