Design of clinical trials for recurrent events with periodic monitoring.
This paper presents a design for randomized clinical trials in which incomplete data are collected on the occurrence of potentially recurrent events through periodic monitoring. In particular, events are assumed to arise according to a point process, but information is available at the times of monitoring only if one or more events has occurred since the preceding monitoring point. The event process is modelled via a piecewise Poisson process, and a proportional rates model is introduced to represent the difference in event rates between treatment groups. The design was developed on the basis of a Wald-type test derived from the generalized estimating equations of Liang and Zeger (Biometrika 73, 13-22 (1986)). Robustification of the variance of the estimator of the treatment effect was considered under a random effects model with a semi-parametric mixture distribution. The design was adopted to address issues which arose in an osteoporosis trial conducted in Japan.
Matsui
S
S
Department of Industrial Management and Engineering, Faculty of Engineering, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162, Japan. matui@oita.nhs.ac.jp
Miyagishi
H
H
D002118:Calcium / Q000627:therapeutic use; D003198:Computer Simulation; D006490:Hemostatics / Q000627:therapeutic use; D006801:Humans; D010024:Osteoporosis / Q000175:diagnosis / Q000188:drug therapy / Q000517:prevention & control; D016012:Poisson Distribution; D016016:Proportional Hazards Models; D011859:Radiography; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design / Q000592:standards*; D013124:Spinal Injuries / Q000175:diagnosis / Q000517:prevention & control; D013131:Spine / Q000000981:diagnostic imaging; D014812:Vitamin K / Q000031:analogs & derivatives / Q000627:therapeutic use; D024482:Vitamin K 2 / Q000031:analogs & derivatives
D006490:Hemostatics; D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D002118:Calcium