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[Meta] the FLOW rule is doing its job and people should stop complaining

Trial Data Receipts ×6 Long Haul ×1

Putting this to the board: the FLOW rule is doing its job and people should stop complaining.

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.

Corrections welcome, especially the pedantic ones. Pedantry is how this board earns its reputation.

1,733 up / 297 down85% upvoted44 commentsid 10byhs22 Jun 2026

44 comments

30 in this archive, depth 5

best — the order this archive was captured in

u/aurel_mwangi123 points·1 months ago

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.

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u/week_four_wall43 points·1 months ago

Agreed. Half the arguments on this site are two people quoting different trials at each other without noticing.

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u/eu_apotheke_a-7 points·1 months ago

Yes. The appendix tables are where the subgroup and the adverse event detail actually live.

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u/ferran_dahlberg1 point·1 months ago

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

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u/cold_chromatogram31-10 points·1 months ago

a press release is not a publication

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u/yusuf_ramos81 points·1 months 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/careful_gradient_againOP35 points·1 months 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/receipts_or_nothingvetting18 points·1 months ago

Relative risk reduction without the baseline rate is uninterpretable. A large relative reduction on a small absolute risk is a small absolute benefit.

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u/gastric_emptying_g0 points·1 months ago

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

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u/eu_apotheke_a1 point·1 months ago

Right — trial participants get structured support. Comparing yourself to a trial mean is comparing across two different interventions.

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u/ahmed_iyer26 points·1 months 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/nordic_pricing38 points·1 months 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/ewan_tulloch10 points·1 months ago

a mean is not a promise

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u/blunt_coldbox_notes3 points·1 months ago

intention to treat versus completers changes the number substantially

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u/careful_gradient_againOP2 points·1 months ago

trial populations get support that nobody on this board gets

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u/careful_gradient_againOP2 points·1 months ago

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

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u/britta_boateng25 points·1 months ago

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.

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u/camila_vasquez11 points·1 months ago

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

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u/rohan_steiner7 points·1 months ago

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

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u/valeria_karlsen16 points·1 months ago

Absolute or relative risk reduction?

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u/ines_boateng20 points·1 months ago

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

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u/hazard_ratio_halMOD15 points·1 months ago

Press-release posts get their own flair here. Nothing wrong with them, they are just a different kind of claim.

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u/nightowl_injector9 points·1 months ago

Do you have the publication or the press release?

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u/joaquin_trevino10 points·1 months ago

Agreed on comparators. "Superior" means nothing until you know superior to what and at what dose.

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u/yara_mensah6 points·1 months ago

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

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u/anders_karlsen5 points·1 months ago

Correction: SURMOUNT is the obesity programme and SURPASS is the diabetes one. The figure you quoted belongs to the other one.

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u/formulary_fighterappeals1 point·1 months 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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u/week_one_wanda1 point·1 months ago

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

formulary_fighter is right about the programme names. They are different populations with different endpoints.

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u/emil_agyeman2 points·1 months ago

open-label extensions are not the same evidence as the randomised phase

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