Validated Synthetic Patient Generation for Small Longitudinal Cohorts: Coagulation Dynamics Across Pregnancy

Abstract

Small longitudinal cohorts, common in maternal health, rare diseases, and early-phase trials, limit computational modeling because enrollment is slow and the data are too sparse to train reliable models. We present multiplicity-weighted Stochastic Attention (SA), a generative framework based on modern Hopfield networks. Stochastic attention stores real patient profiles as memory patterns in a continuous energy landscape. The resulting distribution is a finite mixture with one component centered on each stored profile. We generated the reported cohort with Langevin dynamics; direct sampling from the same distribution reproduced its fidelity and membership-inference results. Multiplicity weights amplify selected subgroups at inference time without retraining. We applied the method to longitudinal coagulation data from 23 patients, with 72 features measured before pregnancy and during the first and third trimesters. The cohort included three patients with polycystic ovary syndrome and five who developed preeclampsia. Across statistical, structural, and mechanistic tests, including a separately specified coagulation model that was blind to the generator but calibrated on the same cohort, the synthetic profiles closely matched the real profiles under the measures applied at this sample size. A model calibrated on synthetic profiles predicted held-out real-patient TGA measurements as well as one calibrated on real profiles. These results provide proof of concept for using SA in the tested modeling tasks, including mechanistic calibration and hypothesis generation, with very small longitudinal cohorts.