Ancova Approach For Shelf Life Analysis Of Stability Study Of Multiple Factor Designs

• Published in: Journal of biopharmaceutical statistics Vol. 13; no. 3; pp. 375 - 393
• Main Authors: Tsong, Yi, Chen, Wen-Jen, Chen, Chi Wan
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 01.08.2003
• Subjects: ANCOVA; Drug Stability; Drug Storage - standards; Drug Storage - statistics & numerical data; Models, Statistical; Multiple factor design; Multivariate Analysis; Shelf life; Stability study; Time Factors
• ISSN: 1054-3406; 1520-5711
• DOI: 10.1081/BIP-120022761

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. # This paper represents the authors' professional opinion but it does not represent the official position of the Food and Drug Administration.