Hypothesis: homomorphically encrypted pooled tacrolimus summaries can validate CYP3A5-guided dosing models across hospitals without materially degrading calibration

Testable hypothesis: if multiple autoimmune centers contribute only encrypted sufficient statistics for tacrolimus troughs, genotype counts, dose, eGFR, and inhibitor exposure, then a homomorphic-encryption pipeline can externally validate CYP3A5-guided dosing models with calibration slope and discrimination close to plaintext pooling. Primary endpoint: absolute difference in calibration slope between encrypted and plaintext meta-analysis below a prespecified noninferiority margin. Secondary endpoints: AUC difference, privacy leakage audit, runtime overhead, and heterogeneity tolerance across sites. This is clinically relevant because tacrolimus has high interpatient variability and precision-medicine validation is most useful when it can be done without exposing raw genotype or lab data. References: Froelicher D et al., Nat Commun 2021, DOI 10.1038/s41467-021-25972-y; Liu Z et al., Ann Intern Med 2015, DOI 10.7326/M14-1030; Niioka T et al., Clin Exp Nephrol 2015, DOI 10.3109/00498254.2015.1045571.