TY - JOUR

T1 - The calculation of historical control limits in toxicology

T2 - Do's, don'ts and open issues from a statistical perspective

AU - Menssen, Max

N1 - Funding Information: I greatly have to thank Frank Schaarschmidt, Markus Schulz and Christina Ziemann for helpful comments and discussions. Furthermore, I have to thank all the members of the statistics working group of the German Society for Environmental Mutation Research (GUM) for all the discussions on HCD and for their encouragement without which this manuscript would never have been written. Many thanks to the reviewers for their time they spent on this manuscript, as well as for their helpful comments.

PY - 2023/11

Y1 - 2023/11

N2 - For reporting toxicology studies, the presentation of historical control data and the validation of the concurrent control group with respect to historical control limits have become requirements. However, many regulatory guidelines fail to define how such limits should be calculated and what kind of target value(s) they should cover. Hence, this manuscript is aimed to give a brief review on the methods for the calculation of historical control limits that are in use as well as on their theoretical background. Furthermore, this manuscript is aimed to identify open issues for the use of historical control limits that need to be discussed by the community. It seems that, even after 40 years of discussion, more issues remain open than solved, both, with regard to the available methodology as well as its implementation in user-friendly software. Since several of these topics equally apply to several research fields, this manuscript is addressed to all relevant stakeholders who deal with historical control data obtained from toxicological studies, regardless of their background or field of research.

AB - For reporting toxicology studies, the presentation of historical control data and the validation of the concurrent control group with respect to historical control limits have become requirements. However, many regulatory guidelines fail to define how such limits should be calculated and what kind of target value(s) they should cover. Hence, this manuscript is aimed to give a brief review on the methods for the calculation of historical control limits that are in use as well as on their theoretical background. Furthermore, this manuscript is aimed to identify open issues for the use of historical control limits that need to be discussed by the community. It seems that, even after 40 years of discussion, more issues remain open than solved, both, with regard to the available methodology as well as its implementation in user-friendly software. Since several of these topics equally apply to several research fields, this manuscript is addressed to all relevant stakeholders who deal with historical control data obtained from toxicological studies, regardless of their background or field of research.

KW - Assay validation

KW - Bioassay

KW - Historical control data

KW - OECD guidelines

KW - Prediction interval

KW - Tolerance interval

UR - http://www.scopus.com/inward/record.url?scp=85172000107&partnerID=8YFLogxK

U2 - 10.1016/j.mrgentox.2023.503695

DO - 10.1016/j.mrgentox.2023.503695

M3 - Article

VL - 892

JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

SN - 1383-5718

M1 - 503695

ER -