Ways of measuring rates of recurrent events

Abstract

Recurrent events are common in medical research, yet the best ways to measure their occurrence remain controversial. Moreover, the correct statistical techniques to compare the occurrence of such events across populations or treatment groups are not widely known. In both observational studies and randomised clinical trials one natural and intuitive measure of occurrence is the event rate, defined as the number of events (possibly including multiple events per person) divided by the total person-years of experience. This is often a more relevant and clinically interpretable measure of disease burden in a population than considering only the first event that occurs. Appropriate statistical tests to compare such event rates among treatment groups or populations require the recognition that some individuals may be especially likely to experience recurrent events. Straightforward approaches are available to account for this tendency in crude and stratified analyses. Recently developed regression models can appropriately examine the association of several variables with rates of recurrent events. Many diseases and other clinical outcomes may recur in the same patient. Examples include asthma attacks, skin cancers, myocardial infarctions, injuries, migraines, seizures in epileptics, and admissions to hospital. Another type of repeated event occurs when a disease can affect paired or multiple organs separately, such as cataract affecting a second eye or cavities in multiple teeth. What measures to use to quantify the occurrence of such conditions remains controversial in both clinical trials and observational studies.1 2 3 4 5 6 Inappropriate statistical approaches are often used to compare rates of recurrent events.6 Although statistical approaches based on sound principles exist, the methodological issues surrounding the study of recurrent events have received insufficient attention in the clinical and epidemiological literature.4 5 Windeler and Lange presented several examples of clinical trials in which multiple events in the same participant …