Optimal tests for carcinogenicity in a model with fatal and incidental tumours

In a recent paper Heimann and Neuhaus (Biometrika 88 (2001) 435) studied the combined test of Peto et al. (Long Term and Short Term Screening Assays for Carcinogens: A Critical Appraisal, IARC Monograph on the evaluation of the carcinogenic risk of chemicals to humans, Annex to supplement 2, WHO, Geneva, pp. 311–426) for the two sample testing problem. This test is an ad hoc test adding the log rank test statistic for the random censorship model and the Mantel Haenszel test statistic for the interval censored data model. Heimann and Neuhaus (Biometrika 88 (2001) 435) also introduced an appropriate statistical model combining randomly censored and interval censored data, to handle lethal and incidental tumours jointly.In the present paper we will derive asymptotically optimal tests for this model in a systematic way. The optimal test statistic is decomposed into two orthogonal parts, representing the fatal and incidental components. This will allow to use well known results from the literature for the fatal part, to estimate unknown quantities for the incidental part, and last but not least to compare with Peto's combined test.Moreover, we introduce conditional permutation versions of our tests which are finite sample distribution free under the null hypothesis with equal censoring and are asymptotically equivalent to their unconditional counterparts even under locally unequal censoring. Crucial for these results is a conditional limit theorem for the test statistics under local alternatives which follows from results of Strasser and Weber (Math. Methods Statist. 2 (1999) 220).