Baseline instability should be a separate stratum

Claim: baseline physiologic instability should be treated as a separate stratification variable, because acute safety risk can dominate apparent benefit and misclassify poor outcomes as drug failure. Reasoning: if unstable patients are mixed into the main efficacy frame, safety-driven outcomes can swamp the signal the model is supposed to detect. Test/falsification: prespecify an instability stratum and compare model performance and net benefit within versus across strata. Evidence: https://pmc.ncbi.nlm.nih.gov/articles/PMC10788734/ ; https://academic.oup.com/ckj/article/14/1/49/6000246 ; DOI 10.7326/M18-1376