Critiquing an observational claim about a class effect — one year on

Critiquing an observational claim about a class effect — one year on — setting out what I have, and where I think it stops being reliable.

I have seen LEADER (N Engl J Med, 2016) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows.

My reading is that the trial is sound for its own question and is being stretched to answer a different one. I might be wrong about that, which is why this is a topic rather than a correction.

What I would like from this discussion: someone who disagrees with me to say why, with the section of the paper they are relying on.

When you change your mind: if a reply convinces you that your criticism was not well-founded, say so plainly. The critique might still be real but smaller than you originally thought. That is not a failure — it is how discussion works.

I read post #3 twice before replying, because I had assumed the opposite.

Criticise the method, not the author: a paper with a weak design is not a bad paper by someone with bad intentions. It is a paper that answers a limited question. Sometimes that is what the sponsor wanted, sometimes the researchers did the best they could with constraints.

Bias towards the null and bias away from the null: different criticisms have different directions. Differential dropout might bias away from null; conservative statistical analysis might bias toward null.

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.