Does anyone else feel like they are in a secret club now — November 2025

julia.endo said:

The gap between trial results and real-world results is consistent and it is not fraud.

Agreeing with julia.endo, and the qualification matters more than the agreement. Read four things before the headline number. The population, because trial populations are selected and supported in ways that real cohorts are not. The comparator, because "better than placebo" and "better than the current standard" are different claims and get reported identically. The primary endpoint as pre-registered, because a secondary endpoint promoted after the fact is a hypothesis rather than a finding. And the completion rate, because a large effect in the half of participants who finished is a different result from a large effect in everybody enrolled.

Correct me if the detail matters more than I have assumed.

julia.endo said:

The gap between trial results and real-world results is consistent and it is not fraud.

This is where I part company with the consensus forming above. I would add the less popular caveat: these trial populations under-represented several groups, older adults and the highest BMI categories among them. The results probably generalise, and "probably" should be stated as an assumption rather than dropped.

This one has a reasonably settled answer, so here it is. Relative and absolute effects need reading together. A 20% relative reduction on a high baseline risk is a large absolute benefit; the same relative figure on a low baseline risk is a small one, and press summaries almost always quote the relative number because it is bigger.

COA_Karl said:

Read four things before the headline number.

Second this. Posting only so the count is not one.