mike_nyc said:

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

mike_nyc 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 statins for secondary prevention. That's a strong clinical argument for this approach.

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

What did you change at the same time, and can you separate the two now?

labquiet_amy said:

mike_nyc said: ...regarding the trial evidence...

Forest plot interpretation for the the trial evidence meta-analysis: when reading the pooled estimate, pay attention to:

1. Point estimate (HR/RR/OR) — center of the diamond
2. Confidence interval width — precision of the estimate
3. I² statistic — heterogeneity across studies
4. Individual study weights — are results driven by one large trial?
5. Prediction interval — range of plausible true effects in future settings

The the trial evidence meta-analysis shows a pooled RR of 0.75 (95% CI 0.68-0.85), I²=33%. This is a robust and consistent effect.

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.

PedsEndoPhilly said:

Forest plot interpretation for the the trial evidence meta-analysis: when reading the pooled estimate, pay attention to: Point estimate (HR/RR/OR) —…

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.