Response to criticisms of the USFDA parametric approach for withdrawal time estimation: rebuttal and comparison to the nonparametric method proposed by Concordet and Toutain

The benefits and drawbacks of using nonparametric methods for estimating pr oduct withdrawal times have been debated for many years. This issue was rec ently revived by Concordet & Toutain (1997a, b) when they described a nonpa rametric method for withdrawal time estimation. The authors urged the inter national adoption of this approach, basing their recommendation on three fu ndamental concerns: (1) the lack of a consistent official procedure for det ermining a withdrawal time within the European Union (EU); (2) the need to identify a statistical method for improving the international harmonization of withdrawal times for new chemical entities; and (3) a lack of confidenc e in the robustness of the US Food and Drug Administration/Center for Veter inary Medicine (US FDA) procedure, particularly with respect to minor viola tions in the underlying parametric assumptions. Due to the critical nature of these issues, the US FDA considers it vital t o respond to these concerns. This paper provides a description of the US FD A parametric procedure. We also examine the statistical concerns expressed by Concordet and Toutain, identifying the reasons for our confidence in the US FDA parametric approach. Finally, using their Monte Carlo simulation mo dels, we generate additional datasets to explore the behaviour of their non parametric procedure and evaluate its ability to support US FDA regulatory activities.