CONDITIONAL AND UNCONDITIONAL TESTS WITH HISTORICAL CONTROLS

Score statistics utilizing historical control data have been proposed to test for increasing trend in tumour occurrence rates in laboratory carcinogenicity studies. Novel invariance arguments are used to confirm, under slightly weaker conditions, previously established asymptotic distributions (mixtures of normal distributions) of tests unconditional on the tumor response rate in the concurrent control group. Conditioning on the control response rate, an ancillary statistic, leads to a new conditional limit theorem in which the test statistic converges to an unknown random variable. Because of this, a subasymptotic approximation to the conditional limiting distribution is also considered. The adequacy of these large-sample approximations in finite samples is evaluated using computer simulation. Bootstrap methods for use in finite samples are also proposed. The application of the conditional and unconditional tests is illustrated using bioassay data taken from the literature. The results presented in this paper are used to formulate recommendations for the use of tests for trend with historical controls in practice.