Fold-stratified cross-validation for unbiased and privacy-preserving federated learning

Objective: We introduce fold-stratified cross-validation, a validation methodology that is compatible with privacy-preserving federated learning and that prevents data leakage caused by duplicates of electronic health records (EHRs). Materials and Methods: Fold-stratified cross-validation complements cross-validation with an initial stratification of EHRs in folds containing patients with similar characteristics, thus ensuring that duplicates of a record are jointly present either in training or in validation folds. Monte Carlo simulations are performed to investigate the properties of fold-stratified cross-validation in the case of a model data analysis using both synthetic data and MIMIC-III (Medical Information Mart for Intensive Care-III) medical records. Results: In situations in which duplicated EHRs could induce overoptimistic estimations of accuracy, applying fold-stratified cross-validation prevented this bias, while not requiring full deduplication. However, a pessimistic bias might appear if the covariate used for the stratification was strongly associated with the outcome. Discussion: Although fold-stratified cross-validation presents low computational overhead, to be efficient it requires the preliminary identification of a covariate that is both shared by duplicated records and weakly associated with the outcome. When available, the hash of a personal identifier or a patient's date of birth provides such a covariate. On the contrary, pseudonymization interferes with fold-stratified cross-validation, as it may break the equality of the stratifying covariate among duplicates. Conclusion: Fold-stratified cross-validation is an easy-to-implement methodology that prevents data leakage when a model is trained on distributed EHRs that contain duplicates, while preserving privacy.