[Meta] proposal — a flair for FLOW posts
proposal — a flair for FLOW posts. Nothing about this affects the ranking maths, before anyone asks.
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.
I will update this if the picture changes rather than quietly leaving it up.
best — the order this archive was captured in
Relative risk reduction without the baseline rate is uninterpretable. A large relative reduction on a small absolute risk is a small absolute benefit.
Quoted a figure here confidently, got asked whether it was ITT, went and checked, and it was not. Learned something.
Do you have the publication or the press release?
How long was the randomised phase before any extension?
phase 2 finds a dose, phase 3 measures the effect
Not convinced. Cross-trial comparison between two programmes with different populations and designs is not a comparison.
Push back: an open-label extension tells you about the people who stayed. That is a different question.
Left up and flaired Trial Data. The publication is linked rather than the coverage, which is what we ask for.
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.
Spent an evening with the appendix tables and found the subgroup detail that the entire thread had been speculating about.
Agreed on comparators. "Superior" means nothing until you know superior to what and at what dose.
What was the discontinuation rate?
Absolute or relative risk reduction?
Cosigning on discontinuation. It is a result about tolerability and it gets buried every time.
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.
That is a relative risk reduction. Quoting it without the absolute numbers overstates the case considerably.
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.
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.
FLOW was kidney outcomes and it is the one nobody quotes
Yes — the interval is the finding. A point estimate with a wide interval is a hypothesis in a nice font.
STEP is semaglutide obesity, SURMOUNT is tirzepatide obesity, they are not interchangeable
Yes — the interval is the finding.
Adding the check nobody runs — the registered protocol is public and takes two minutes to compare.
Argued for a week about a result and then read the limitations section, which conceded most of my opponent’s point.
- 1Left up and flaired Trial Data. The publication is linked rather than the…6 comments in this branch · started by u/forest_plot_fiona