SURPASS — 4 things I got wrong before I got it right
SURPASS — 4 things I got wrong before I got it right. Change my mind, genuinely — I have no stake in being right about this.
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.
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.
Open-label extensions lose their randomisation. Anybody still enrolled at week 104 is a selected group and the numbers describe that group.
Sceptical readings welcome. The confident ones are the ones I distrust.
best — the order this archive was captured in
A confidence interval is the range of effects compatible with the data. Two trials with overlapping intervals have not disagreed, whatever their point estimates look like next to each other.
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.
How long was the randomised phase before any extension?
Intention-to-treat analyses everybody randomised regardless of what they did afterwards. Completer analyses only those who finished. The second is systematically more flattering and both are legitimate if labelled.