title: Sensitivity analyses for partially observed recurrent event data.
abstract: Recurrent events involve the occurrences of the same type of event repeatedly over time and are commonly encountered in longitudinal studies. Examples include seizures in epileptic studies or occurrence of cancer tumors. In such studies, interest lies in the number of events that occur over a fixed period of time. One considerable challenge in analyzing such data arises when a large proportion of patients discontinues before the end of the study, for example, because of adverse events, leading to partially observed data. In this situation, data are often modeled using a negative binomial distribution with time-in-study as offset. Such an analysis assumes that data are missing at random (MAR). As we cannot test the adequacy of MAR, sensitivity analyses that assess the robustness of conclusions across a range of different assumptions need to be performed. Sophisticated sensitivity analyses for continuous data are being frequently performed. However, this is less the case for recurrent event or count data. We will present a flexible approach to perform clinically interpretable sensitivity analyses for recurrent event data. Our approach fits into the framework of reference-based imputations, where information from reference arms can be borrowed to impute post-discontinuation data. Different assumptions about the future behavior of dropouts dependent on reasons for dropout and received treatment can be made. The imputation model is based on a flexible model that allows for time-varying baseline intensities. We assess the performance in a simulation study and provide an illustration with a clinical trial in patients who suffer from bladder cancer.
authors.affiliation: Novartis Pharma AG, Statistical Methods & Consulting Group, Basel, Switzerland.
authors.forename: Mouna
authors.initials: M
authors.lastname: Akacha
authors.affiliation: Centre for Statistics in Medicine, University of Oxford, Oxford, UK.
authors.forename: Emmanuel O
authors.initials: EO
authors.lastname: Ogundimu
mesh_terms: D002986:Clinical Trials as Topic / Q000592:standards / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D006801:Humans; D010352:Patient Dropouts / Q000706:statistics & numerical data; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology
keywords: count data; missing data; pattern-mixture models; recurrent event data; sensitivity analyses