Uniformization and bounded Taylor series in Newton–Raphson method improves computational performance for a multistate transition model estimation and inference

Multistate transition models (MSTMs) are valuable tools depicting disease progression. However, due to the complexity of MSTMs, larger sample size and longer follow-up time in real-world data, the computation of statistical estimation and inference for MSTMs becomes challenging. A bounded Taylor series in Newton-Raphson procedure is proposed which leverages the uniformization technique to derive maximum likelihood estimates and corresponding covariance matrix. The proposed method, namely uniformization Taylor-bounded Newton-Raphson, is validated in three simulation studies, which demonstrate the accuracy in parameter estimation, the efficiency in computation time and robustness in terms of different situations. This method is also illustrated using a large electronic medical record data related to statin-induced side effects and discontinuation.