how much of what we believe about endpoint actually comes from STEP threads
how much of what we believe about endpoint actually comes from STEP threads. I would rather ask a basic question now than get this wrong quietly for two months. Spent an evening with the appendix tables and found the subgroup detail that the entire thread had been speculating about. Quoted a figure here confidently,…
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.
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.
open-label extensions are not the same evidence as the randomised phase
Went looking for the registered protocol to see whether the endpoint had changed. It had not, which was reassuring and worth checking.
The discontinuation numbers were the most useful thing in the paper for me and they were in a supplementary table.
Started keeping the trial identifiers straight in a note file because I kept mixing up two programmes in the same sentence.