SURPASS — 15 things I got wrong before I got it right
The title is the argument: SURPASS — 15 things I got wrong before I got it right. Here is the rest of it.
Discontinuation rates are a tolerability result. A trial with a strong efficacy number and heavy discontinuation is telling you two things and people only quote one.
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.
Relative risk reduction without the baseline rate is uninterpretable. A large relative reduction on a small absolute risk is a small absolute benefit.
Corrections welcome, especially the pedantic ones. Pedantry is how this board earns its reputation.
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.
Open-label extensions lose their randomisation. Anybody still enrolled at week 104 is a selected group and the numbers describe that group.
Open-label extensions lose their randomisation.
This is the distinction that would end about half the arguments on this board.
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.
check who the comparator was before you compare anything
Argued for a week about a result and then read the limitations section, which conceded most of my opponent’s point.
Push back: an open-label extension tells you about the people who stayed. That is a different question.
Quoted a figure here confidently, got asked whether it was ITT, went and checked, and it was not. Learned something.
Agreed on comparators. "Superior" means nothing until you know superior to what and at what dose.
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.
intention to treat versus completers changes the number substantially
That is a relative risk reduction. Quoting it without the absolute numbers overstates the case considerably.
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.
STEP is semaglutide obesity, SURMOUNT is tirzepatide obesity, they are not interchangeable
STEP is semaglutide obesity, SURMOUNT is tirzepatide obesity, they are not interchangeable
Agreed. And the interval, not the point estimate, is what the trial actually established.
Agreed.
Adding the check nobody runs — the registered protocol is public and takes two minutes to compare.
phase 2 finds a dose, phase 3 measures the effect
the appendix is where the interesting tables live
registry entry, protocol, publication — three different documents
Spent an evening with the appendix tables and found the subgroup detail that the entire thread had been speculating about.
Spent an evening with the appendix tables and found the subgroup detail that the entire thread had been speculating about.
careful_gradient_again is right about the programme names. They are different populations with different endpoints.
Read a press release and the publication three months apart. The hedging in the second one was substantial.
read the endpoint before you read the headline
read the endpoint before you read the headline
Disagreeing with this line: that is a relative reduction and the absolute numbers are considerably less dramatic.
Careful with that mean. The distribution around it was wide enough that it describes very few individual participants.
Disagree — that figure is from the diabetes programme and you are quoting it as an obesity endpoint.
- 1Read a press release and the publication three months apart. The hedging in…7 comments in this branch · started by u/hamza_zielinski
- 2Intention-to-treat analyses everybody randomised regardless of what they did…6 comments in this branch · started by u/hub_ops