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- Harry Yang, Steven J Novick, and David LeBlond.
- a MedImmune, LLC , Gaithersburg , Maryland , USA.
- J Biopharm Stat. 2015 Jan 1; 25 (2): 339-50.
AbstractValidation of linearity is a regulatory requirement. Although many methods are proposed, they suffer from several deficiencies including difficulties of setting fit-for-purpose acceptable limits, dependency on concentration levels used in linearity experiment, and challenges in implementation for statistically lay users. In this article, a statistical procedure for testing linearity is proposed. The method uses a two one-sided test (TOST) of equivalence to evaluate the bias that can result from approximating a higher-order polynomial response with a linear function. By using orthogonal polynomials and generalized pivotal quantity analysis, the method provides a closed-form solution, thus making linearity testing easy to implement.
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