On the use of historical control information for trend test in carcinogenesis.

Abstract

In this article a new non-model-based significance test for detecting dose-response relationship with the incorporation of historical control data is proposed. This non-model-based test is considered simpler from a regulatory perspective because it does not require validating any modeling assumptions. Moreover, our test is especially appropriate to those studies in which the intravenous doses for the investigational chemical are labeled as, e.g., low, medium and high or the dose labels do not suggest any obvious choices of dose scores. This test can be easily adopted for detecting general dose-response shape, such as an umbrella pattern. Simple adjustments will be proposed for better control of the actual Type I error. Data sets from two carcinogenesis studies will be used to illustrate our method. We also evaluate the performance of the proposed test and the famous model-based Tarone's trend test with respect to size and power.