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

unpopular opinion: most of what gets said here about hazard ratio is guesswork

Trial Data Cold Box ×1 Clean Column ×2 Receipts ×2

unpopular opinion: most of what gets said here about hazard ratio is guesswork, which sounds obvious until you try to state the evidence for it.

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

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.

9,123 up / 920 down91% upvoted40 commentsid 16eybf21 Jan 2024

40 comments

30 in this archive, depth 5

best — the order this archive was captured in

u/milan_villalobos798 points·2 years 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/enzo_ferrari367 points·2 years ago

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

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u/hugo_bergstrom198 points·2 years ago

Cosigning on discontinuation. It is a result about tolerability and it gets buried every time.

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u/nightowl_injector497 points·2 years 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/pancreatitis_scareOP238 points·2 years ago

What did the confidence interval look like?

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u/ferran_dahlberg341 points·2 years ago

The press release said that; the publication says something more hedged. Worth reading both.

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u/injection_site_iris76 points·2 years ago·edited

Do you have the publication or the press release?

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u/tomas_kimani273 points·2 years ago

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.

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u/heart_rate_bump139 points·2 years ago

FLOW was kidney outcomes and it is the one nobody quotes

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u/cold_chromatogram31-12 points·2 years ago

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

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u/ms_fragmenter1 point·2 years ago

read the endpoint before you read the headline

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u/alcohol_aversion1 point·2 years 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/foam_head_fred1 point·2 years 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/pancreatitis_scare1 point·2 years ago

SURPASS is the diabetes programme and reports glycaemic endpoints

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u/customs_seizure_sid1 point·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/rulebook_rachaelmod · c/meta159 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/ines_castellanos69 points·2 years ago

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

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u/nhs_waitlist_nUK16 points·2 years ago

discontinuation rate is a result, not a footnote

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u/zaid_roos105 points·2 years ago

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

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[removed]75 points·2 years ago

[removed by moderator]

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u/yusuf_ramos129 points·2 years ago

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

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u/hazard_ratio_halMOD95 points·2 years ago

Retitled: the original quoted a diabetes endpoint as an obesity result.

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u/cesar_ivaturi35 points·2 years ago

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

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u/pancreatitis_scareOP39 points·2 years ago

Is that intention-to-treat or completers?

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u/tb500_tangent0 points·2 years ago

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

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u/anders_kuusela1 point·2 years ago

phase 2 finds a dose, phase 3 measures the effect

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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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