Identifying methodologies in the assessment of treatment effects on the repeated occurrences of hot flashes in postmenopausal womenClinical Biostatistics, Merck Research Labs, Merck & Co., Inc., Rahway, NJ, USA
Department of Statistics, George Washington University, Washington DC, USA Background Two methods that are commonly used in most clinical trials for evaluating the effect of treatment on hot flashes are frequency only and severity score methods. However, in these crude methods, composite recurrent hot flash data on a patient are reduced to a one-dimensional summary measure, an approach which may not be optimal. In addition, the duration of a hot flash event provides additional information, which is not accounted for in the two methods mentioned above. Purpose We propose two new methods in the analysis of hot flash data in this paper. Methods The first method utilizes a generalization of the continuation ratio model to model the severity of a hot flash event. The model accounts for individual random effects and dependence of recurrent events within an individual. The other method that accounts for the duration of a hot flash event is a 3-Dimensional (3D) score method, which incorporates hot flash information on frequency, severity, and duration. Results Simulation studies were conducted to evaluate the properties of our proposed methods. The results indicate that our proposed generalized continuation ratio model has appreciably high power in detecting small treatment effects on severity compared with the two commonly used methods. The proposed 3D score, on the other hand, is sensitive in detecting treatment effects on both frequency and duration, but has low power in detecting treatment effects on severity alone. Conclusions Our proposed generalized continuation ratio model approach provides a valuable and powerful alternative to the two commonly used methods in the analysis of treatment effects on hot flash severity. Our proposed 3D score method incorporates the additional information hot flash duration provides, and is another analysis option for the practitioners to employ.
Clinical Trials, Vol. 2, No. 6,
497-508 (2005) |
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