title: Testing assay linearity over a pre-specified range.
abstract: Validation 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.
authors.affiliation: a MedImmune, LLC , Gaithersburg , Maryland , USA.
authors.forename: Harry
authors.initials: H
authors.lastname: Yang
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Novick
authors.forename: David
authors.initials: D
authors.lastname: LeBlond
mesh_terms: D015982:Bias; D001702:Biopharmaceutics / Q000592:standards / Q000706:statistics & numerical data*; D002626:Chemistry, Pharmaceutical; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D017408:Guidelines as Topic; D016014:Linear Models; D015233:Models, Statistical; D011786:Quality Control; D012016:Reference Values; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data*
keywords: Equivalence test; Fieller’s exact confidence interval; Generalized pivotal quantity; Linearity testing; Orthogonal regression