how much of what we believe about endpoint actually comes from FLOW threads
Question in the title, detail here: how much of what we believe about endpoint actually comes from FLOW threads.
Went looking for the registered protocol to see whether the endpoint had changed. It had not, which was reassuring and worth checking.
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.
Argued for a week about a result and then read the limitations section, which conceded most of my opponent’s point.
If somebody has the same thing measured a different way, post it next to mine and we will see whether they agree.
best — the order this archive was captured in
Retitled: the original quoted a diabetes endpoint as an obesity result.
read the endpoint before you read the headline
intention to treat versus completers changes the number substantially
SURPASS is the diabetes programme and reports glycaemic endpoints
Small fix — that was the cardiovascular outcomes trial, so weight was a secondary endpoint and the population was different.
Cosigning on discontinuation. It is a result about tolerability and it gets buried every time.
discontinuation rate is a result, not a footnote
How long was the randomised phase before any extension?
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.
Correction: SURMOUNT is the obesity programme and SURPASS is the diabetes one. The figure you quoted belongs to the other one.
Absolute or relative risk reduction?
Do you have the publication or the press release?
Do you have the publication or the press release?
Agreed. And the interval, not the point estimate, is what the trial actually established.
Is that intention-to-treat or completers?
Agreed.
Disagreeing with this line: that is a relative reduction and the absolute numbers are considerably less dramatic.
[deleted]
What did the confidence interval look like?
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.
That is the 68-week readout, not the 72-week one. Different trial, different duration.
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.
SELECT was cardiovascular outcomes, not weight
Disagree — that figure is from the diabetes programme and you are quoting it as an obesity endpoint.
- 1Retitled: the original quoted a diabetes endpoint as an obesity result.9 comments in this branch · started by u/forest_plot_fiona
- 2Absolute or relative risk reduction?7 comments in this branch · started by u/milos_trevino