Analysis of recurrent events: application to a clinical trial of colony stimulating factor with the endpoint of febrile neutropenia.
This paper discusses the analysis of randomized clinical trials where the primary endpoint is a recurrent event observed during a time period which can vary among patients. In particular it describes a method of estimating robust confidence limits for clinically relevant parameters. As an illustrative example, a clinical trial of a macrophage colony stimulating factor (M-CSF) for patients with acute myeloblastic leukaemia (AML) is introduced where the endpoint is the incidence and duration of febrile neutropenia. The causal effects in the framework of Rubin's deterministic model are defined as estimands. A non-parametric method based on the permutation test, using an accelerated search procedure proposed by Garthwaite, is compared with other standard methods by simulation and by application to the AML trial data.
Matsui
S
S
Division of Health Informatics and Biostatistics, Department of Health Sciences, Oita University of Nursing and Health Sciences, 2944-9 Megusuno, Notsuharu-machi, Oita 870-1201, Japan. matui@oita-nhs.ac.jp
Ohashi
Y
Y
D003198:Computer Simulation; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D005334:Fever / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D016173:Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D015337:Multicenter Studies as Topic; D009503:Neutropenia / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012008:Recurrence; D018709:Statistics, Nonparametric; D013269:Stochastic Processes
D016173:Macrophage Colony-Stimulating Factor