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Journal of Antibodies
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Vessel Plus
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Research in Ecology
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Annals of Urology

How then did T attain its overwhelming supremacy? As I was once offered $750 by the T sponsor to attend a dinner extolling PLATO’s benefits by a leading writer of the Canadian guidelines (I declined), one must wonder about the role of marketing in overcoming any scientific shortcomings.

Thus even ignoring questionable data integrity, T superiority in PLATO attributed to the choice of statistical model. While one may choose to reject the proposed hierarchical model as better, should be a consensus if conclusions vary drastically according to model choice, data not considered robust.

2nd US study not done. Later RCTs not kind to T. Asian trial, genetic reasons to expect T superiority, showed not the expected improved but worse outcomes with T (HR, 1.47; 95% CI: 0.88-2.44). RCT elderly Dutch pts also worse T outcomes (RD -4%, 95% CI -10.0 to 1.4; p=0.03 for NI).

Ignoring this uncertainty lead to publications and guidelines proclaiming T superiority, when a more reasonable interpretation is that while there appears to be a positive T signal this needs confirmation in further studies, especially for US patients.

IOW, even accepting the PLATO data as is, choosing a more realistic statistical model with a better estimate of the underlying the uncertainty we see that conventional statistical significance for T is no longer met.

But the overall summary mean will have wider confidence intervals (HRmean 0.90 95% CIs 0.72-1.10) as this now includes both within and between region sampling variations. The next, as yet unperformed, study is predicted to fall in the 95% CI 0.46 – 1.37 interval.

This model gives a US HR 1.05 95% CIs 0.79-1.35. As predicted, the regional US estimate is shrunk towards the global mean with improved precision due to this borrowing of information.

Hierarchical modeling, a compromise btw no & complete pooling, provides optimal statistical properties & offers a sortie from this quandary. Individual country / region effects are shrunken towards the global mean and their variance is improved by this borrowing of information from other regions.

Ignoring clustering within regions underestimates the sampling errors resulting in falsely precise confidence intervals. OTOH, examining only the US subgroup is wasteful as it excludes 90% of available data.

Apparently corporate reassurance prevailed and instead of looking at subgroups, the FDA accepted the pooled results. Implies strong assumption that all ancillary post MI care is identical whether the patient was randomized in Bulgaria, South Africa or any of the other 41 participating countries.