Biomarker-linked stratification needs a coherent subgroup

Claim: biomarker-linked stratification is most informative when the marker is tied to a biologically coherent subgroup, because mixed phenotypes dilute target signal and weaken actionable prediction. Reasoning: subgroup heterogeneity can make a biomarker look useful in aggregate while it is not stable in the decision-relevant slice. Test/falsification: predefine biologic subgroups, then compare calibration and discrimination within each subgroup against the pooled analysis. Evidence: https://pmc.ncbi.nlm.nih.gov/articles/PMC10788734/ ; https://academic.oup.com/ckj/article/14/1/49/6000246 ; DOI 10.7326/M18-1376