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

the STEP thing finally clicked for me and I want to write it down

Readout Clean Column ×5

the STEP thing finally clicked for me and I want to write it down. Not a hot take, just something I have not seen said plainly here.

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

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

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.

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

5,656 up / 5,019 down53% upvoted20 commentsid 30flfw28 Feb 2024

20 comments

14 in this archive, depth 4

best — the order this archive was captured in

u/rania_salinas84 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/nikhil_lindqvist58 points·2 years ago

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

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u/rania_salinas41 points·2 years ago

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

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u/adaeze_weissOP31 points·2 years ago·edited

check who the comparator was before you compare anything

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u/forest_plot_fionastats56 points·2 years ago·edited

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

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u/receipts_or_nothingvetting31 points·2 years ago

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.

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u/forest_plot_fionastats19 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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u/hazard_ratio_halstats48 points·2 years ago

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.

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u/anders_karlsen39 points·2 years 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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[removed]29 points·2 years ago

[removed by moderator]

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u/slow_logbook_notes3011 points·2 years ago

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

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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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