how much of what we believe about endpoint actually comes from hazard ratio threads
Asking properly rather than in a comment on somebody else’s thread: how much of what we believe about endpoint actually comes from hazard ratio threads.
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.
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 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.
Ask me anything specific. Anything general I will probably get wrong.
best — the order this archive was captured in
Retitled: the original quoted a diabetes endpoint as an obesity result.
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open-label extensions are not the same evidence as the randomised phase
the confidence interval is the finding, the point estimate is the headline
phase 2 finds a dose, phase 3 measures the effect
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.
Small fix — that was the cardiovascular outcomes trial, so weight was a secondary endpoint and the population was different.
SURPASS is the diabetes programme and reports glycaemic endpoints
What did the confidence interval look like?
Yes. The appendix tables are where the subgroup and the adverse event detail actually live.