Discussion on statistical analysis of carcinogenicity studies with an early terminated treated group

SUMMARY High rates of mortality on long term carcinogenicity studies can often result in challenges when it comes to the statistical analysis of tumor incidence. The current regulatory advice often results in treated groups being terminated earlier than the control group. However, this advice rarely considers the impact of this action on the statistical analyses. The nature of these analyses means that groups terminated at different times may not be directly comparable due to age differences of the animals. Here we discuss the issues related to this and investigate several approaches of how to incorporate these groups within the statistical analyses. Although no single method appears to resolve these issues consistently, inclusion of the early terminated group is still informative. Depending on the timing of the early termination, either pooling of the groups into a single terminal kill (TK) interval or reassignment of intervals based purely on time of death (ie, no separate TK interval) appear preferable. However, to draw meaningful conclusions the time of onset of a given tumor must also be considered alongside incident rates and any statistical findings.