Weekly check-in thread — need advice

pete_manc_UK said:

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

Pushing back on pete_manc_UK here. 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.

Happy to go further on any of that.

greg_boulder said:

My own curve sits about four points below the published mean and I spent two months assuming that meant something was wrong with me or with my…

greg_boulder said:

...regarding the trial evidence...

I think this is an underappreciated point. To expand on it with some data:

A recent meta-analysis of 15 RCTs (n=12,300) found that the trial evidence was associated with a clinically meaningful effect size across diverse patient populations[1].

The NNT was 12, which is comparable to antihypertensives for stroke reduction. That's a strong clinical argument for this approach.

Dr.AddMedPHL said:

I would add the less popular caveat: these trial populations under-represented several groups, older adults and the highest BMI categories among them.

Bayesian meta-analysis perspective on the trial evidence: traditional frequentist meta-analyses report point estimates and confidence intervals. Bayesian approaches provide probability distributions that are more intuitive for clinical decision-making.

For example: "There is a 98.5% probability that semaglutide 2.4mg produces >10% weight loss vs placebo" is more actionable than "RR 3.4, 95% CI 2.8-4.1, p<0.001."

The the trial evidence evidence is strong under both frameworks, but Bayesian analysis better communicates the degree of certainty for individual patient counseling.

One thing that is still open after tom_AK’s answer:

What would you measure differently if you were starting again?

Reporting back.

Update — my curve sits below the published mean and the explanation is that the trial arm had support I do not have. That was reassuring rather than otherwise.