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c/trialwatch·posted 2 years ago by u/joaquin_trevino

genuine question about TRIUMPH that I am slightly embarrassed to ask

Trial Data Clean Column ×2 Cold Box ×1 Long Haul ×1

Trying to get a straight answer on this: genuine question about TRIUMPH that I am slightly embarrassed to ask.

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.

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.

Not medical advice, obviously, and nothing here is approved for human use. One person with a spreadsheet.

4,330 up / 1,087 down80% upvoted48 commentsid 4edlwr24 Apr 2024

48 comments

30 in this archive, depth 5

best — the order this archive was captured in

u/anders_karlsen387 points·2 years ago

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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u/cold_chromatogram31120 points·2 years ago

What did the confidence interval look like?

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u/tove_ogunleye56 points·2 years ago

the confidence interval is the finding, the point estimate is the headline

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u/joaquin_trevinoOP-8 points·2 years ago

the confidence interval is the finding, the point estimate is the headline

Agreed. And the interval, not the point estimate, is what the trial actually established.

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u/joaquin_trevinoOP0 points·2 years ago

Correcting myself upthread: I gave the completer figure and labelled it intention-to-treat.

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u/whois_wanda36 points·2 years ago

a mean is not a promise

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u/renal_outcomes_rnephro-curious8 points·2 years ago

trial populations get support that nobody on this board gets

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u/ferran_dahlberg202 points·2 years ago

Careful with that mean. The distribution around it was wide enough that it describes very few individual participants.

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u/milan_villalobos161 points·2 years ago

Disagree — that figure is from the diabetes programme and you are quoting it as an obesity endpoint.

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u/renal_outcomes_rnephro-curious189 points·2 years ago

Spent an evening with the appendix tables and found the subgroup detail that the entire thread had been speculating about.

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u/yara_mensah65 points·2 years ago

Not convinced. Cross-trial comparison between two programmes with different populations and designs is not a comparison.

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u/ms_fragmenter47 points·2 years ago

Compared myself to a trial mean for about six months before realising the trial arm had dietitian contact every fortnight.

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u/joaquin_trevinoOP29 points·2 years ago

STEP is semaglutide obesity, SURMOUNT is tirzepatide obesity, they are not interchangeable

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u/tove_ogunleye6 points·2 years ago

discontinuation rate is a result, not a footnote

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u/rina_bergstrom131 points·2 years ago

Push back: an open-label extension tells you about the people who stayed. That is a different question.

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u/adaeze_cabrera123 points·2 years ago

Quoted a figure here confidently, got asked whether it was ITT, went and checked, and it was not. Learned something.

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u/joaquin_stanescu77 points·2 years ago

Quoted a figure here confidently, got asked whether it was ITT, went and checked, and it was not.

Adding the check nobody runs — the registered protocol is public and takes two minutes to compare.

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u/iman_castellanos92 points·2 years ago

FLOW was kidney outcomes and it is the one nobody quotes

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u/naomi_ekstrom40 points·2 years ago

Small fix — that was the cardiovascular outcomes trial, so weight was a secondary endpoint and the population was different.

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u/week_one_wanda58 points·2 years ago·edited

Went looking for the registered protocol to see whether the endpoint had changed. It had not, which was reassuring and worth checking.

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u/yara_mensah16 points·2 years ago

Same. A press release is a claim about a result; the publication is the result.

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u/ms_fragmenter10 points·2 years ago

That is a relative risk reduction. Quoting it without the absolute numbers overstates the case considerably.

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u/joaquin_trevino16 points·2 years ago

This. Intention-to-treat versus completer analysis routinely moves the headline by several points.

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[removed]40 points·2 years ago

[removed by moderator]

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u/marit_laurent26 points·2 years ago

That is the 68-week readout, not the 72-week one. Different trial, different duration.

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u/pancreatitis_scare56 points·2 years ago

Is that intention-to-treat or completers?

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u/emil_agyeman41 points·2 years ago

The discontinuation numbers were the most useful thing in the paper for me and they were in a supplementary table.

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