title: ANCOVA approach for shelf life analysis of stability study of multiple factor designs.
abstract: For a traditional multiple batch stability design with no other factor, the conventional analysis is analysis of covariance (ANCOVA) modeling using F-tests based on type I sum of squares to determine whether the batches may be pooled for a common estimate of the linear regression line(s). In the last decade, many multiple factor designs were proposed in stability studies. With the objective of model selection, the generalization of the conventional ANCOVA model using type I sum of squares to designs with multiple factors requires a prespecified hierarchical pooling test ordering to determine whether any of the factors may be eliminated. Different shelf life estimates may be derived using different hierarchical pooling test orderings. On the other hand, setting the hierarchical ordering can be subjective and controversial. The stepwise modeling based on F-tests using type III sum of squares for model determination and factor elimination is proposed to eliminate such difficulties.
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, FDA, Rockville, Maryland 20857, USA. tsong@cder.fda.gov
authors.forename: Yi
authors.initials: Y
authors.lastname: Tsong
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Chen
authors.forename: Chi Wan
authors.initials: CW
authors.lastname: Chen
mesh_terms: D004355:Drug Stability; D004356:Drug Storage / Q000592:standards / Q000706:statistics & numerical data; D015233:Models, Statistical; D015999:Multivariate Analysis; D013997:Time Factors