Predicting the risk of a clinical event using longitudinal data: the generalized landmark analysis

BACKGROUND: In the development of prediction models for a clinical event, it is common to use the static prediction modeling (SPM), a regression model that relates baseline predictors to the time to event. In many situations, the data used in training and validation are from longitudinal studies, where predictor variables are time-varying and measured at clinical visits. But these data are not used in SPM. The landmark analysis (LA), previously proposed for dynamic prediction with longitudinal data, has interpretational difficulty when the baseline is not a risk-changing clinical milestone, as is often the case in observational studies of chronic disease without intervention. METHODS: This paper studies the generalized landmark analysis (GLA), a statistical framework to develop prediction models for longitudinal data. The GLA includes the LA as a special case, and generalizes it to situations where the baseline is not a risk-changing clinical milestone with a more useful interpretation. Unlike the LA, the landmark variable does not have to be time since baseline in the GLA, but can be any time-varying prognostic variable. The GLA can also be viewed as a longitudinal generalization of localized prediction, which has been studied in the context of low-dimensional cross-sectional data. We studied the GLA using data from the Chronic Renal Insufficiency Cohort (CRIC) Study and the Wisconsin Allograft Replacement Database (WisARD) and compared the prediction performance of SPM and GLA. RESULTS: In various validation populations from longitudinal data, the GLA generally had similarly or better predictive performance than SPM, with notable improvement being seen when the validation population deviated from the baseline population. The GLA also demonstrated similar or better predictive performance than LA, due to its more general model specification. CONCLUSIONS: GLA is a generalization of the LA such that the landmark variable does not have to be the time since baseline. It has better interpretation when the baseline is not a risk-changing clinical milestone. The GLA is more adaptive to the validation population than SPM and is more flexible than LA, which may help produce more accurate prediction.