I hypothesize that homomorphically encrypted or privacy-preserving sufficient-statistic pooling can preserve clinically useful external validation of TMP-SMX hyperkalemia models across decentralized autoimmune cohorts, without exposing patient-level potassium or medication histories.

Claim

If each site shares encrypted aggregates or sufficient statistics for:

• baseline potassium distribution,
• eGFR strata,
• ACEi/ARB exposure,
• spironolactone/eplerenone exposure,
• treatment-dose versus prophylaxis-only TMP-SMX,
• and observed hyperkalemia events,

then a pooled validation workflow can recover transportability signals close to those from centralized analysis for calibration slope, calibration-in-the-large, and subgroup performance.

Why this matters

Autoimmune cohorts are fragmented across hospitals, private clinics, and research networks. Raw laboratory sharing is often blocked by privacy, governance, and cross-border constraints. If encrypted aggregation preserves model validation quality, decentralized drug-safety science becomes much more feasible.

Testable design

• Multicenter retrospective or prospective validation network.
• Compare centralized raw-data validation versus encrypted pooled sufficient-statistic validation.
• Primary outcomes: difference in calibration slope, Brier score, and subgroup AUROC across CKD, RAAS-blocker, and spironolactone strata.
• Acceptability margin: predefine clinically acceptable non-inferiority bounds for calibration loss.

Falsification

The hypothesis fails if encrypted pooling produces clinically unacceptable degradation in calibration or subgroup performance compared with centralized validation.

References

1. Fralick M, et al. BMJ. 2014;349:g6196. DOI: 10.1136/bmj.g6196
2. Antoniou T, et al. Arch Intern Med. 2010;170(12):1045-1049. DOI: 10.1001/archinternmed.2010.271
3. Velázquez H, et al. Ann Intern Med. 1993;119(4):296-301. DOI: 10.7326/0003-4819-119-4-199308150-00003

Topics: FHE, DeSci, biostatistics, decentralized clinical validation.