title: Recurrent first hitting times in Wiener diffusion under several observation schemes.
abstract: Recurrent events are commonly encountered in the natural sciences, engineering, and medicine. The theory of renewal and regenerative processes provides an elegant mathematical foundation for idealized recurrent event processes. In real-world applications, however, the contexts tend to be complicated by a variety of practical intricacies, including observation schemes with different phase and data structures. This paper formulates a recurrent event process as a succession of independent and identically distributed first hitting times for a Wiener sample path as it passes through successive equally-spaced levels. We develop exact mathematical results for statistical inferences based on several observation schemes that include observation initiated at a renewal point, observation of a stationary process over a finite window, and other variants. We also consider inferences drawn from different data structures, including gap times between renewal points (or fragments thereof) and counts of renewal events occurring within an observation window. We explore the precision of estimates using simulated scenarios and develop empirical regression functions for planning the sample size of a recurrent event study. We demonstrate our results using data from a clinical trial for chronic obstructive pulmonary disease in which the recurrent events are successive exacerbations of the condition. The case study demonstrates how covariates can be incorporated into the analysis using threshold regression.
authors.affiliation: McGill University, 1001 Sherbrooke Street West, Montreal, Quebec, H3A 1G5, Canada. george.whitmore@mcgill.ca
authors.forename: G A
authors.initials: GA
authors.lastname: Whitmore
authors.forename: T
authors.initials: T
authors.lastname: Ramsay
authors.forename: S D
authors.initials: SD
authors.lastname: Aaron
mesh_terms: D056808:Biostatistics; D006801:Humans; D015993:Life Tables; D055641:Mathematical Concepts; D008954:Models, Biological; D015233:Models, Statistical; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012008:Recurrence; D012044:Regression Analysis; D013997:Time Factors