Guidance for statistical design and analysis of toxicological dose–response experiments, based on a comprehensive literature review

Abstract

The analysis of dose–response, concentration–response, and time–response relationships is a central component of toxicological research. A major decision with respect to the statistical analysis is whether to consider only the actually measured concentrations or to assume an underlying (parametric) model that allows extrapolation. Recent research suggests the application of modelling approaches for various types of toxicological assays. However, there is a discrepancy between the state of the art in statistical methodological research and published analyses in the toxicological literature. The extent of this gap is quantified in this work using an extensive literature review that considered all dose–response analyses published in three major toxicological journals in 2021. The aspects of the review include biological considerations (type of assay and of exposure), statistical design considerations (number of measured conditions, design, and sample sizes), and statistical analysis considerations (display, analysis goal, statistical testing or modelling method, and alert concentration). Based on the results of this review and the critical assessment of three selected issues in the context of statistical research, concrete guidance for planning, execution, and analysis of dose–response studies from a statistical viewpoint is proposed.