A systematic assessment of robustness in CNS safety pharmacology

The multicenter study ‘A systematic assessment of robustness in CNS safety pharmacology’ aimed to assess the robustness of Irwin tests across multinational sites during three stages of protocol harmonization. Neurofunctional testing in animals is essential to characterize drug-induced effects on the CNS prior to first-in-human trials (ICH S7A). With this multicenter approach, we aimed to determine the impact of environmental, experimental, and scoring-related variables on Irwin outcome measures, assessing between-site variability during three consecutive stages of protocol harmonization. The projects were part of the EQIPD consortium (Enhanced Quality in Preclinical Data, https://quality-preclinical-data.eu/; https://go-eqipd.org/). EQIPD is a consortium of scientists from academia and industry that aims to improve the robustness of preclinical data generated in animal studies. In particular, the EQIPD consortium aims to identify factors that influence the quality of data generated in preclinical research in order to provide recommendations for a successful transition from preclinical research to the clinic.

Raw datasets
Stage 1
1_Dataset_EQIPD-Irwin_Stage1_Domains.xlsx2_Dataset_EQIPD-Irwin_Stage1_Site1.xlsx3_Dataset_EQIPD-Irwin_Stage1_Site2.xlsx4_Dataset_EQIPD-Irwin_Stage1_Site3.xlsx5_Dataset_EQIPD-Irwin_Stage1_Site4.xlsx6_Dataset_EQIPD-Irwin_Stage1_Site5.xlsx7_Dataset_EQIPD-Irwin_Stage1_Domain-other-measures.xlsxDatasets 1, 2, 3, 4, 5, and 6 underlie Figure 2. Dataset 7 underlies Supplementary Figures 1, 2, 3, 4, and 5.

Stage 2
8_Dataset_EQIPD-Irwin_Stage2_Domains.xlsx9_Dataset_EQIPD-Irwin_Stage2_Site1.xlsx10_Dataset_EQIPD-Irwin_Stage2_Site2.xlsx11_Dataset_EQIPD-Irwin_Stage2_Site3.xlsx12_Dataset_EQIPD-Irwin_Stage2_Site4.xlsx13_Dataset_EQIPD-Irwin_Stage2_Site5.xlsx14_Dataset_EQIPD-Irwin_Stage2_Domain-other-measures.xlsxDatasets 8, 9, 10, 11, 12, and 13 underlie Figure 3. Dataset 14 underlies Supplementary Figures 6, 7, 8, 9, and 10.

Stage 3
15_Dataset_EQIPD-Irwin_Stage3_Domains.xlsx16_Dataset_EQIPD-Irwin_Stage3_Masterfile-Binary.xlsx17_Dataset_EQIPD-Irwin_Stage3_Sites1-2-3.xlsx18_Dataset_EQIPD-Irwin_Stage3_Domain-other-measures.xlsx19_Dataset_EQIPD-Irwin_Stage3_Site4.xlsx20_Dataset_EQIPD-Irwin_Stage3_Site4_Domain-other-measures.xlsxDatasets 15, 16, and 17 underlie Figures 4 and 5. Dataset 18 underlies Supplementary Figure 11. Dataset 19 underlies Supplementary Figure 12. Dataset 20 underlies Supplementary Figure 13.