Accepted answer
Fair depends on the comparator arm, and in STEP 5 that means asking whether the comparator was titrated to the same ambition as the experimental one. A head-to-head that runs its comparator to a dose below the one it is licensed at is not measuring the two agents, it is measuring one agent against a handicapped version of the other. Check three things: the maximum comparator dose reached, the proportion of the comparator arm that reached it, and whether the titration schedules had the same duration. If those match, the comparison is fair on dosing and the argument moves to the endpoint. If they do not, the effect size is partly an artefact of the protocol.
The part that matters: the trial answers a narrower question than the headline suggests, and the narrowing is where the useful information is.
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.
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.
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.
If a claim cannot be traced to a named trial with a named endpoint, treat it as a claim rather than as evidence.
edited 18 Sept 2024 by jo_vandeberg — fixed an arithmetic slip in the third paragraph
8The placebo-arm figure is the part everyone omits. – v_ramaswamy 11 days ago 7Minor: the trial name is hyphenated in the original publication. – kwn_analytical 9 months ago add a comment