State space model multiple imputation for missing data in non-stationary multivariate time series with application in digital Psychiatry

Mobile technology enables unprecedented continuous monitoring of an individual's behavior, social interactions, symptoms, and other health conditions, presenting an enormous opportunity for therapeutic advancements and scientific discoveries regarding the etiology of psychiatric illness. Continuous collection of mobile data results in the generation of a new type of data: entangled multivariate time series of outcome, exposure, and covariates. Missing data is a pervasive problem in biomedical and social science research, and the Ecological Momentary Assessment (EMA) using mobile devices in psychiatric research is no exception. However, the complex structure of multivariate time series introduces new challenges in handling missing data for proper causal inference. Data imputation is commonly recommended to enhance data utility and estimation efficiency. The majority of available imputation methods are either designed for longitudinal data with limited follow-up times or for stationary time series, which are incompatible with potentially non-stationary time series. In the field of psychiatry, non-stationary data are frequently encountered as symptoms and treatment regimens may experience dramatic changes over time. To address missing data in possibly non-stationary multivariate time series, we propose a novel multiple imputation strategy based on the state space model (SSMmp) and a more computationally efficient variant (SSMimpute). We demonstrate their advantages over other widely used missing data strategies by evaluating their theoretical properties and empirical performance in simulations of both stationary and non-stationary time series, subject to various missing mechanisms. We apply the SSMimpute to investigate the association between social network size and negative mood using a multi-year observational smartphone study of bipolar patients, controlling for confounding variables.