Clinical prediction models in children that use repeated measurements with time-varying covariates: a scoping review

BACKGROUND: Emerging evidence suggests that clinical prediction models that use repeated (time-varying) measurements within each patient may have higher predictive accuracy than models that use patient information from a single measurement. OBJECTIVE: To determine the breadth of the published literature reporting the development of clinical prediction models in children that use time-varying predictors. DATA SOURCES: MEDLINE, EMBASE and Cochrane databases. ELIGIBILITY CRITERIA: We included studies reporting the development of a multivariable clinical prediction model in children, with or without validation, to predict a repeatedly measured binary or time-to-event outcome and utilizing at least one repeatedly measured predictor. SYNTHESIS METHODS: We categorized included studies by the method used to model time-varying predictors. RESULTS: Of 99 clinical prediction model studies that had a repeated measurements data structure, only 27 (27%) used methods that incorporated the repeated measurements as time-varying predictors in a single model. Among these 27 time-varying prediction model studies, we grouped model types into nine categories: time-dependent Cox regression, generalized estimating equations, random effects model, landmark model, joint model, neural network, K-nearest neighbor, support vector machine and tree-based algorithms. Where there was comparison of time-varying models to single measurement models, using time-varying predictors improved predictive accuracy. CONCLUSIONS: Various methods have been used to develop time-varying prediction models in children, but there is a paucity of pediatric time-varying models in the literature. Incorporating time-varying covariates in pediatric prediction models may improve predictive accuracy. Future research in pediatric prediction model development should further investigate whether incorporation of time-varying covariates improves predictive accuracy.