[Discussion] the endpoint advice in here is 3 years out of date
The title is the argument: the endpoint advice in here is 3 years out of date. Here is the rest of it.
To save the first four comments: 3 years.
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.
Why comparing across trials almost never works, with the specific failure modes.
Different populations: an obesity programme and a diabetes programme enrol different people with different baseline characteristics. Different endpoints: body weight change, glycaemic control and cardiovascular events are not convertible. Different durations: 68 weeks and 72 weeks are not the same, and the curves have not flattened by either.
Different analysis populations: one paper reports intention-to-treat, another emphasises completers. Different support: some trial designs include structured lifestyle contact that no member of this board receives.
Stack those and the "X beats Y" tables that circulate here are comparing five things at once and attributing the difference to the molecule.
Not medical advice, obviously, and nothing here is approved for human use. One person with a spreadsheet.
best — the order this archive was captured in
The registered protocol is public. Comparing the registered primary endpoint with the reported one is a two-minute check and it is how outcome switching gets caught.
read the endpoint before you read the headline
That is the 68-week readout, not the 72-week one. Different trial, different duration.
registry entry, protocol, publication — three different documents
Agreed. Half the arguments on this site are two people quoting different trials at each other without noticing.
Small fix — that was the cardiovascular outcomes trial, so weight was a secondary endpoint and the population was different.
Read a press release and the publication three months apart. The hedging in the second one was substantial.
the appendix is where the interesting tables live
discontinuation rate is a result, not a footnote
SURPASS is the diabetes programme and reports glycaemic endpoints
Same. A press release is a claim about a result; the publication is the result.
Is that intention-to-treat or completers?
Yes. The appendix tables are where the subgroup and the adverse event detail actually live.
Yes.
Agreed. And the interval, not the point estimate, is what the trial actually established.
open-label extensions are not the same evidence as the randomised phase
How long was the randomised phase before any extension?
Yes — the interval is the finding. A point estimate with a wide interval is a hypothesis in a nice font.