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c/trialwatch·posted 12 months ago by u/milan_villalobos

[Discussion] the endpoint advice in here is 3 years out of date

Discussion Clean Column ×5 Well Actually ×1

the endpoint advice in here is 3 years out of date. It is the sort of thing everyone half-believes and nobody writes down.

3 years. Those are measured, not estimated, and not rounded up in my favour.

Argued for a week about a result and then read the limitations section, which conceded most of my opponent’s point.

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.

That is everything I have. The rest is opinion and I have tried to keep it out.

2,545 up / 389 down87% upvoted49 commentsid 5itzsa31 Jul 2025

49 comments

30 in this archive, depth 5

best — the order this archive was captured in

u/cold_chromatogram31429 points·12 months ago

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.

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u/nightowl_injector338 points·12 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/nayeli_fonseca355 points·12 months ago

Discontinuation rates are a tolerability result.

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

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u/milan_villalobosOP194 points·12 months ago·edited

SELECT was cardiovascular outcomes, not weight

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u/trialwatch_theotrial nerd151 points·12 months ago·edited

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

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u/adaeze_cabrera228 points·12 months ago

SURPASS is the diabetes programme and reports glycaemic endpoints

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u/milan_villalobosOP154 points·12 months ago

registry entry, protocol, publication — three different documents

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u/ines_boateng128 points·12 months ago·edited

FLOW was kidney outcomes and it is the one nobody quotes

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u/yara_mensah43 points·12 months ago

read the endpoint before you read the headline

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u/nightowl_injector188 points·12 months ago

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

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u/hsa_math59 points·12 months ago

How long was the randomised phase before any extension?

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u/cesar_ivaturi48 points·12 months ago·edited

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

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u/naomi_ekstrom15 points·12 months ago

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

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u/renal_outcomes_rMOD111 points·12 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/rohan_steiner131 points·12 months ago

discontinuation rate is a result, not a footnote

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u/anders_vermeulen29 points·12 months ago

Absolute or relative risk reduction?

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u/gastric_emptying_g53 points·12 months ago

Is that intention-to-treat or completers?

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[deleted]122 points·12 months ago

[deleted]

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u/marit_laurent84 points·12 months ago

Yes — the interval is the finding. A point estimate with a wide interval is a hypothesis in a nice font.

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u/injection_site_iris161 points·12 months ago

phase 2 finds a dose, phase 3 measures the effect

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u/sten_palacios45 points·12 months ago·edited

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

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u/forest_plot_fionastats53 points·12 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/careful_gradient_again-16 points·12 months ago

Started keeping the trial identifiers straight in a note file because I kept mixing up two programmes in the same sentence.

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u/rina_bergstrom43 points·12 months ago

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

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u/rania_salinas24 points·12 months ago·edited

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

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u/milan_villalobosOP18 points·12 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/anders_kuusela7 points·12 months ago

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

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u/joaquin_trevino2 points·12 months ago

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

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u/yara_mensah2 points·12 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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Clinical trial reading group. New readouts, protocol amendments, endpoint definitions, dropout handling, and the difference between a press release and a publication. Absolute risk reduction and number-needed-to-treat are house dialect here.

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