Blum et al. published in Alternatives to Animal Experimentation

Jonathan Blum, Markus Brüll, Jan G. Hengstler, Daniel R. Dietrich, Andreas J. Gruber, Michele Dipalo, Udo Kraushaar, Iris Mangas, Andrea Terron, Ellen Fritsche, Philip Marx-Stoelting, Barry Hardy, Andreas Schepky, Sylvia Escher, Thomas Hartung, Robert Landsiedel, Alex Odermatt, Magdalini Sachana, Katharina Koch, Arif Dönmez, Stefan Masjosthusmann, Kathrin Bothe, Stefan Schildknecht, Mario Beilmann, Joost B. Beltman, Suzanne Fitzpatrick, Aswin Mangerich, Markus Rehm, Silvia Tangianu, Franziska M. Zickgraf, Hennicke Kamp, Gerhard Burger, Bob van de Water, Nicole Kleinstreuer, Andrew White, Marcel Leist

Toxicological test methods generate raw data and provide instructions on how to use these to determine a final outcome such as a classification of test compounds as hits or non-hits. The data processing pipeline provided in the test method description is often highly complex. Usually, multiple layers of data, ranging from a machine-generated output to the final hit definition, are considered. Transition between each of these layers often requires several data processing steps. As changes in any of these processing steps can impact the final output of new approach methods (NAMs), the processing pipeline is an essential part of a NAM description and should be included in reporting templates such as the ToxTemp. The same raw data, processed in different ways, may result in different final outcomes that may affect the readiness status and regulatory acceptance of the NAM, as an altered output can affect robustness, performance, and relevance. Data management, pro­cessing, and interpretation are therefore important elements of a comprehensive NAM definition. We aim to give an overview of the most important data levels to be considered during the devel­opment and application of a NAM. In addition, we illustrate data processing and evaluation steps between these data levels. As NAMs are increasingly standard components of the spectrum of toxi­cological test methods used for risk assessment, awareness of the significance of data processing steps in NAMs is crucial for building trust, ensuring acceptance, and fostering the reproducibility of NAM outcomes.

Toxicological test methods initially generate raw data. These need to be further processed to determine a final outcome, such as the classification of test compounds as hits or non-hits. The pro­cessing of the raw data is often highly complex and proceeds stepwise. This process generates many layers of data connected by several processing steps. Any change to these processing steps can impact the final output of new approach methods (NAMs). This means that the same raw data, processed in different ways, may result in different final outcomes. Data management, processing and interpretation are therefore considered important elements of a comprehensive NAM definition. We illustrate data processing and evaluation steps that play an important role. Awareness of the significance of data processing steps in NAMs is crucial for building trust, ensuring acceptance, and fostering the reproducibility of NAM outcomes.