title: The design and analysis of randomized trials with recurrent events.
abstract: This paper describes a method for planning the duration of a randomized parallel group study in which the response of interest is a potentially recurrent event. At the design stage we assume patients accrue at a constant rate, we model events via a homogeneous Poisson process, and we utilize an independent exponential censoring mechanism to reflect loss to follow-up. We derive the appropriate study duration to ensure satisfaction of power requirements for the effect size of interest under a Poisson regression model. An application to a kidney transplant study illustrates the potential savings of the Poisson-based design relative to a design based on the time to the first event. Revised design criteria are also derived to accommodate overdispersed Poisson count data. We examine the frequency properties of two non-parametric tests recently proposed by Lawless and Nadeau for trials based on the above design criteria. In simulation studies involving homogeneous and non-homogeneous Poisson processes they performed well with respect to their type I error rate and power. Results from supplementary simulation studies indicate that these tests are also robust to extra-Poisson variation and to clustering in the event times, making these tests attractive in their generality. We illustrate both tests by application to data from a completed kidney transplant study.
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, Canada.
authors.forename: R J
authors.initials: RJ
authors.lastname: Cook
mesh_terms: D000465:Algorithms; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D015987:Effect Modifier, Epidemiologic; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology; D016853:Muromonab-CD3 / Q000627:therapeutic use; D016012:Poisson Distribution; D011817:Rabbits; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012008:Recurrence; D015203:Reproducibility of Results; D012107:Research Design; D018401:Sample Size; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3