Optimal design theory of dose-response experiments in toxicology
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Date
2025
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Abstract
New research approaches of sciences like statistics and toxicology have been coming up through rapid development in the last years. However, those research approaches often refer to only one of the two sciences, not considering important aspects of the other discipline. Especially in the crucial part of planning an experiment, the laboratory routine in toxicology does not consider optimal design theory of statistics, although there is already much research present, which could help to improve the research results. This demonstrates a huge gap between practical applications in toxicological research and existing statistical theory. On the one hand, this gap exists due to the missing statistical methods specifically tailored to toxicological applications, and on the other hand, if those statistical methods exist, they are not reported in a clear manner for non-statisticians. The consequences for toxicological experiments are a waste of observations, or even worse animals, and non-optimal results in terms of precision. Therefore, this is an important aspect in the field of statistics and toxicology, which needs to be addressed. Optimal design approaches specifically tailored to toxicology must be developed and reported appropriately.
This cumulative thesis is based on three works, that all present optimal design approaches for diverse toxicological applications. The first manuscript highlights the importance of considering optimal design approaches for classical cytotoxicity experiments in a userfriendly manner. Here, different optimal design approaches are compared to typically used designs in practice based on an extensive case study. Moreover, a guideline for cytotoxicity experiments and an R-Shiny software tool are presented, which both facilitate the planning of upcoming cytotoxicity experiments. In the second manuscript a new design approach for the precise estimation of effective dose sets in drug combination studies is developed. For that matter, the performance of the corresponding developed criterion is investigated in a simulation study based on various scenarios including a case study. Finally, a new design approach for the analysis of high-dimensional gene-expression data is developed in the third manuscript. While two of the manuscripts are already published, the second one is attached in its current, unpublished form.
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Keywords
Dose-response, Optimal design
Subjects based on RSWK
Optimale Versuchsplanung, Dosis-Wirkungs-Analyse