Probabilistic assessment method of the non-monotonic dose-responses-Part I: Methodological approach

- A method was established to assess a probabilistic characterization of NMDRCs.
- The methodology is based on a sampling principle and a statistical comparison.
- Characterization is performed according to the definition of the non-monotonicity.
- It is applicable to all data and can be used to characterize all types of curves.
- This study presents the general principle of the method and some results.

More and more studies aim to characterize non-monotonic dose response curves (NMDRCs). The greatest difficulty is to assess the statistical plausibility of NMDRCs from previously conducted dose response studies. This difficulty is linked to the fact that these studies present (i) few doses tested, (ii) a low sample size per dose, and (iii) the absence of any raw data.In this study, we propose a new methodological approach to probabilistically characterize NMDRCs. The methodology is composed of three main steps: (i) sampling from summary data to cover all the possibilities that may be presented by the responses measured by dose and to obtain a new raw database, (ii) statistical analysis of each sampled dose-response curve to characterize the slopes and their signs, and (iii) characterization of these dose-response curves according to the variation of the sign in the slope.This method allows characterizing all types of dose-response curves and can be applied both to continuous data and to discrete data.The aim of this study is to present the general principle of this probabilistic method which allows to assess the non-monotonic dose responses curves, and to present some results.