intent-to-treat vs per-protocol explains half the arguments on this site
intent-to-treat vs per-protocol explains half the arguments on this site. Change my mind, genuinely — I have no stake in being right about this.
On means, which this board treats as targets and which are nothing of the sort.
A reported mean body weight change is the centre of a distribution that in these trials is very wide. Substantial numbers of participants did much better, and substantial numbers did considerably worse while remaining on the drug and in the analysis.
Quoting the mean as an expectation therefore misleads in both directions: it makes ordinary results look like failures and it makes exceptional results look normal. If a paper publishes the distribution — and several do, in the appendix — look at that instead. It is far more informative than the number in the abstract.
Argued for a week about a result and then read the limitations section, which conceded most of my opponent’s point.
How to read one of these papers in fifteen minutes, in the order that actually helps.
Start with the registered protocol and check the primary endpoint against what is reported. Then the methods: who was included, what the comparator was, how long the randomised phase ran. Then the discontinuation numbers, which are a tolerability result and are usually in a supplementary table.
Only then the efficacy figure, and read the interval rather than the point estimate. Finish with the limitations section, which is where the authors say what they actually think.
Fifteen minutes, and you will know more than any thread summarising it.
That is everything I have. The rest is opinion and I have tried to keep it out.
best — the order this archive was captured in
Cardiovascular outcome trials are powered for events, not for weight, and are typically run in a different population with different inclusion criteria. Reading a weight number out of one is reading a secondary endpoint.
Went looking for the registered protocol to see whether the endpoint had changed. It had not, which was reassuring and worth checking.
That is a relative risk reduction. Quoting it without the absolute numbers overstates the case considerably.
registry entry, protocol, publication — three different documents
Push back: an open-label extension tells you about the people who stayed. That is a different question.
This. Intention-to-treat versus completer analysis routinely moves the headline by several points.
Which trial, and which arm?
FLOW was kidney outcomes and it is the one nobody quotes
Cosigning on discontinuation. It is a result about tolerability and it gets buried every time.
the confidence interval is the finding, the point estimate is the headline
That is the 68-week readout, not the 72-week one. Different trial, different duration.
STEP is semaglutide obesity, SURMOUNT is tirzepatide obesity, they are not interchangeable
How long was the randomised phase before any extension?
Retitled: the original quoted a diabetes endpoint as an obesity result.
Is that intention-to-treat or completers?
- 1Push back: an open-label extension tells you about the people who stayed.…11 comments in this branch · started by u/joaquin_trevino