SELECT: what the trials say vs what this community says
SELECT: what the trials say vs what this community says — a position I have arrived at slowly and would like tested.
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
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.
Yes — the interval is the finding. A point estimate with a wide interval is a hypothesis in a nice font.
Yes — the interval is the finding.
This is the distinction that would end about half the arguments on this board.
Went looking for the registered protocol to see whether the endpoint had changed. It had not, which was reassuring and worth checking.
Spent an evening with the appendix tables and found the subgroup detail that the entire thread had been speculating about.
Cosigning on discontinuation. It is a result about tolerability and it gets buried every time.
The discontinuation numbers were the most useful thing in the paper for me and they were in a supplementary table.
Careful with that mean. The distribution around it was wide enough that it describes very few individual participants.
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.
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.
Which trial, and which arm?
Quoted a figure here confidently, got asked whether it was ITT, went and checked, and it was not. Learned something.
Which trial, and which arm?
Agreed. And the interval, not the point estimate, is what the trial actually established.
discontinuation rate is a result, not a footnote
the appendix is where the interesting tables live
Added the trial identifier to the title so this thread is findable in two years.
Correction: SURMOUNT is the obesity programme and SURPASS is the diabetes one. The figure you quoted belongs to the other one.
SELECT was cardiovascular outcomes, not weight
Argued for a week about a result and then read the limitations section, which conceded most of my opponent’s point.
Open-label extensions lose their randomisation. Anybody still enrolled at week 104 is a selected group and the numbers describe that group.
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