Marginal mark regression analysis of recurrent marked point process data

Longitudinal studies typically collect information on the timing of key clinical events and on specific characteristics that describe those events. Random variables that measure qualitative or quantitative aspects associated with the occurrence of an event are known as marks. Recurrent marked point process data consist of possibly recurrent events, with the mark (and possibly exposure) measured if and only if an event occurs. Analysis choices depend on which aspect of the data is of primary scientific interest. First, factors that influence the occurrence or timing of the event may be characterized using recurrent event analysis methods. Second, if there is more than one event per subject, then the association between exposure and the mark may be quantified using repeated measures regression methods. We detail assumptions required of any time-dependent exposure process and the event time process to ensure that linear or generalized linear mixed models and generalized estimating equations provide valid estimates. We provide theoretical and empirical evidence that if these conditions are not satisfied, then an independence estimating equation should be used for consistent estimation of association. We conclude with the recommendation that analysts carefully explore both the exposure and event time processes prior to implementing a repeated measures analysis of recurrent marked point process data.