Translating preclinical insights into early psychopharmacology trials: application of the IB-Derisk analyser tool

Abstract

This thesis explored the application of the IB-Derisk analyser tool in early-phase neuropsychiatric drug development. Late-stage failures in central nervous system (CNS) drug development can be reduced through improved interpretation of preclinical data and early investigation of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics. However, the primary source of preclinical data, the Investigator’s Brochure (IB), is often difficult to interpret due to non-standardised reporting, incomplete data, lack of validated disease models, and missing PK information in efficacy studies. Furthermore, limited communication between preclinical and clinical researchers hampers data integration and interpretation. To overcome these challenges, the IB-Derisk analyser tool was developed. It condenses large, fragmented datasets into a single, one-page, colour-coded overview that can be updated with emerging clinical findings. By aligning data across species and exposure levels, the tool helps identify missing information, potential safety issues, selecting relevant biomarkers, while also facilitating prediction of clinical outcomes. The studies presented in this thesis illustrate how the IB-Derisk analyser tool helps researchers gain a clearer pharmacological understanding of novel compounds, guiding more informed decisions and improving the likelihood of success in later development stages by ensuring that key pharmacological insights are established in early phases of development.