FLOW got published and nobody in here is talking about eGFR slope
The title is the argument: FLOW got published and nobody in here is talking about eGFR slope. Here is the rest of it.
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.
On means, which this board treats as targets and which are nothing of the sort.
A reported mean body weight change is the centre of a distribution that in these trials is very wide. Substantial numbers of participants did much better, and substantial numbers did considerably worse while remaining on the drug and in the analysis.
Quoting the mean as an expectation therefore misleads in both directions: it makes ordinary results look like failures and it makes exceptional results look normal. If a paper publishes the distribution — and several do, in the appendix — look at that instead. It is far more informative than the number in the abstract.
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.
If somebody has the same thing measured a different way, post it next to mine and we will see whether they agree.
best — the order this archive was captured in
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.
This. Intention-to-treat versus completer analysis routinely moves the headline by several points.
discontinuation rate is a result, not a footnote
the confidence interval is the finding, the point estimate is the headline
FLOW was kidney outcomes and it is the one nobody quotes
Careful with that mean. The distribution around it was wide enough that it describes very few individual participants.
Careful with that mean.
Disagreeing with this line: that is a relative reduction and the absolute numbers are considerably less dramatic.
Agreed on comparators. "Superior" means nothing until you know superior to what and at what dose.
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.
Cardiovascular outcome trials are powered for events, not for weight, and are typically run in a different population with different inclusion criteria. Reading a weight number out of one is reading a secondary endpoint.
Open-label extensions lose their randomisation. Anybody still enrolled at week 104 is a selected group and the numbers describe that group.
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.
check who the comparator was before you compare anything
Argued for a week about a result and then read the limitations section, which conceded most of my opponent’s point.
Press-release posts get their own flair here. Nothing wrong with them, they are just a different kind of claim.
SURPASS is the diabetes programme and reports glycaemic endpoints
- 1The registered protocol is public. Comparing the registered primary endpoint…7 comments in this branch · started by u/ines_castellanos