Journal club: SUSTAIN 6 and its retinopathy signal — does this still hold?

The question in the title: Journal club: SUSTAIN 6 and its retinopathy signal — does this still hold? I will give what I have already checked below so nobody repeats it.

Reading SUSTAIN 6 (N Engl J Med, 2016) for the population rather than the effect, which I have not done properly before.

The baseline table is more restrictive than the way the trial gets discussed here. Several of the questions in this category come from people who would not have been enrolled.

What is the honest way to describe what the trial says to somebody outside its population?

The opening post is right about the mechanism and I think understates the practical bit.

The confident answers on SUSTAIN 6 and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category.

Worth separating two things that the opening post runs together.

Reading order that works for these sessions: registry entry, methods, baseline table, primary result, then abstract last. Reading the abstract first anchors everything that follows.

That distinction has done more work for me than anything else in this category.

The most common failure mode is spending fifty minutes on the effect size and ten on the population. Reversing that ratio would improve most sessions.

The disagreement above is smaller than it looks once the terms are fixed.

I had written a reply contradicting post #3 and deleted it. Here is what survived.

Two things can be true about SUSTAIN 6 at once: the mechanism is plausible and the evidence for the size of the effect is thin. Most of the argument here is people defending the first against attacks on the second.

Confirming post #3 from a second method, which matters more than confirming it from a second person.

I keep a log for SUSTAIN 6 specifically because my memory of it turned out to be systematically wrong in one direction. Six weeks of notes cost nothing and settled it.

Noted, and I have changed what I was going to do on the strength of it.

The figures usually contain the finding and the text usually contains the interpretation. Separating them for the first twenty minutes is a discipline worth keeping.

Where I part company with post #8, and it is a narrow parting.

Practical note on SUSTAIN 6: write down what you expect before you look. The number of times I have found what I went looking for is higher than chance would allow.

Sessions on negative or null results are consistently the most instructive and the hardest to get anyone to attend.

Picking up post #8: that is the part I would want checked first.

A definition problem is doing most of the work in this SUSTAIN 6 discussion. Once the term is pinned down I suspect the disagreement mostly goes away and what is left is small.

On post #10 — agreed on the reasoning, with one qualification.

Where the group cannot agree, record the disagreement rather than resolving it by seniority. The recorded disagreement is more honest and more useful later.

Acknowledging rather than arguing. The reasoning holds as far as I can follow it.

I would be cautious about generalising from the SUSTAIN 6 example above. It is a good example. It is one example.