Abstract
The Historical Control Data Working Group, under the direction of the Scientific and Regulatory Policy Committee (SRPC) of the Society of Toxicologic Pathology (STP) was tasked with reviewing the current scientific practices, regulatory guidance, and relevant literature pertaining to rodent microscopic historical control data (HCD) of proliferative lesions to provide best practice recommendations for locating, generating, and applying such data. The Working Group focused exclusively on HCD of proliferative lesions from nonclinical rodent carcinogenicity studies. The HCD Working Group recommends the following consensus principles to guide the use of HCD of proliferative lesions from chronic rodent (rats/mice) bioassays: The concurrent control group is the most relevant comparator for determining treatment-related effects in a study. HCD may be useful in the interpretation of rare tumors, marginally greater incidences and/or severity of proliferative changes in treated animals compared to controls, and unexpected increases or decreases of tumor incidences in study control animals. HCD can be used as a tool to provide scientific perspective of disparate findings in dual concurrent control groups and review trends in tumor biology and behavior that may evolve over time in these rodent models. Study design–related parameters such as laboratory, species/strain, route of administration, vehicle, feed, feeding practices, study duration, and housing have a potential to impact study outcomes and control findings. These parameters should be considered when selecting the appropriate studies for the HCD. Pathology practices, including necropsy and trimming procedures and application of diagnostic criteria, can impact study data and HCD. HCD are best if these factors are standardized. HCD from the laboratory that conducted the study under review will likely be more comparable than HCD compiled from several laboratories. Similarly, HCD that underwent a peer-review process are generally more reliable than those that did not. Published HCD should be evaluated carefully. It may provide guidance in evaluating data associated with particular effects, but difficulties in assessing the quality of published data should be considered along with the “weight of evidence” for determining its relevance to study findings. HCD may be presented as a range of incidences or percentages, mean, and standard deviation for a given change. Reporting of incidences per study will allow both presentation and use of a broad range of observations and provide transparency of potential influences of outlier populations. Although a limited time span of two to seven years for collection of HCD is proposed in the guidance documents of several agencies, wider intervals may be appropriate if tumor types are stable over a longer period. HCD should be considered as one of many sources of information that add to the “weight of evidence” approach when assessing the potential carcinogenic effect of a compound.