[Meta] the FLOW rule is doing its job and people should stop complaining
the FLOW rule is doing its job and people should stop complaining. Nothing about this affects the ranking maths, before anyone asks.
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.
Argued for a week about a result and then read the limitations section, which conceded most of my opponent’s point.
How to read one of these papers in fifteen minutes, in the order that actually helps.
Start with the registered protocol and check the primary endpoint against what is reported. Then the methods: who was included, what the comparator was, how long the randomised phase ran. Then the discontinuation numbers, which are a tolerability result and are usually in a supplementary table.
Only then the efficacy figure, and read the interval rather than the point estimate. Finish with the limitations section, which is where the authors say what they actually think.
Fifteen minutes, and you will know more than any thread summarising it.
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.
Spent an evening with the appendix tables and found the subgroup detail that the entire thread had been speculating about.
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.
Cosigning on discontinuation. It is a result about tolerability and it gets buried every time.
open-label extensions are not the same evidence as the randomised phase
What did the confidence interval look like?
That is a relative risk reduction. Quoting it without the absolute numbers overstates the case considerably.
intention to treat versus completers changes the number substantially
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STEP is semaglutide obesity, SURMOUNT is tirzepatide obesity, they are not interchangeable
The press release said that; the publication says something more hedged. Worth reading both.
Is that intention-to-treat or completers?
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.
- 1open-label extensions are not the same evidence as the randomised phase6 comments in this branch · started by u/tove_ogunleye