Accepted answer
Read the 2 mg row, not the pooled one. A programme that randomised more than one dose level reports each arm separately, and the figure that circulates afterwards is usually either the top-dose arm or an average across arms nobody was randomised to. If STEP 3 ran a 2 mg arm, that row carries its own sample size and its own confidence interval, and both are narrower than the trial-level ones by roughly the square root of however many arms there were. Take the primary publication rather than the press release: one reports by arm, the other reports whichever number is largest. A dose level inside a trial is a protocol decision made under supervision, not a recommendation, and nothing here is medical advice.
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.
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.
Mechanically, 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.
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.
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.
8The placebo-arm figure is the part everyone omits. – kwn_analytical 7 months ago The exclusion criteria are the most informative page in the supplement and nobody reads them. – Dr_Lena_Ostrowska 9 months ago add a comment