the STEP thing finally clicked for me and I want to write it down
the STEP thing finally clicked for me and I want to write it down. Not a hot take, just something I have not seen said plainly here.
Spent an evening with the appendix tables and found the subgroup detail that the entire thread had been speculating about.
Relative risk reduction without the baseline rate is uninterpretable. A large relative reduction on a small absolute risk is a small absolute benefit.
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.
Please do not ask me what dose you should be on. I genuinely do not know and neither does anyone else here.
best — the order this archive was captured in
Open-label extensions lose their randomisation. Anybody still enrolled at week 104 is a selected group and the numbers describe that group.
Left up and flaired Trial Data. The publication is linked rather than the coverage, which is what we ask for.
Yes. The appendix tables are where the subgroup and the adverse event detail actually live.
Compared myself to a trial mean for about six months before realising the trial arm had dietitian contact every fortnight.
discontinuation rate is a result, not a footnote
What was the comparator?
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.
Went looking for the registered protocol to see whether the endpoint had changed. It had not, which was reassuring and worth checking.
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.
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.
trial populations get support that nobody on this board gets
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.
[deleted]
the confidence interval is the finding, the point estimate is the headline
SELECT was cardiovascular outcomes, not weight
open-label extensions are not the same evidence as the randomised phase
How long was the randomised phase before any extension?
read the endpoint before you read the headline
That is the 68-week readout, not the 72-week one. Different trial, different duration.
- 1Why comparing across trials almost never works, with the specific failure…8 comments in this branch · started by u/cloudy_vial_carol