Thanks, very useful and interesting article.

From the outset I was a little confused at Don’s optimism about a bolt-on trial.

If we assume repeating BETonMACE with greater numbers is not on the cards, what are we left with to develop ABL for a cardiovascular outcome under BT status?

A new study in patients on SGLT2/DPP4 inhibitors is certainly possible, but without more information about the ABL and placebo groups on the inhibitors we don’t know how strong that evidence is. It’s theoretically quite possible that the patients who were given ABL were slimmer, had lower LDL cholesterol kevels, had lower blood pressure, had fewer smokers, etc than the placebo group. I know I’ve mention this sort of thing before, but it’s frustrating that Don never addresses this fundamental issue whenever he describes subgroup analyses. It’s the first thing a statistician would want to look at.

In my opinion, the reduction in CHF readmissions is the most promising result in BETonMACE when it comes getting approval. The fact it was a secondary endpoint is not such a big deal. It was statistically significant and was in the total sample, not a subgroup.

If I were the driving seat, this is what I would focus on for the BT designation for CVD. But of course I’m not! And the FDA has no doubt seen more data than we have.