A likelihood ratio test for cancer screening trials

In randomized cancer screening trials, mortality rates for the screened group relative to those of the control group are not likely to be constant as a function of years from randomization due to the inherent lag between initiation of screening and any putative effects of screening on mortality. In this situation, a log rank test for differences in mortality between the randomization groups will not be optimal. Although optimality could potentially be recovered by use of a weighted log rank statistic, the optimal weights are difficult to specify a priori and the potential loss of power by use of poorly specified weights is great. We describe a likelihood ratio test with two degrees of freedom for use in this situation which is based on a fit of a weakly structured full model. Computation of an approximate significance level for this test is described and a large sample justification for this approximation is given. Size and power properties of the proposed statistic are compared to that of several other statistics in a small simulation study and the statistic is applied to data from the HIP Breast Cancer Screening Trial.