Last November, the ERAMET project was presented at this year’s Pharmacokinetics UK (PKUK) meeting, an important event where experts in drug research gather to share ideas and advancements. This two-day meeting took place in Bracknell, England, and provided a platform for discussing the latest progress in pharmacokinetics and pharmacodynamics (PKPD).
At the event, Linda Wanika, a Research Fellow from the University of Warwick, presented the ERAMET project during a session on “Paediatric and Rare Disease Application”. Linda’s presentation focused on the model development process, highlighting areas requiring credibility assessments and where AI tools can aid these assessments. The exemplar scientific question of interest (QOI) was:
What are the best tetrabenazine (TBZ) dosing schedules for children (2-11 years) with Juvenile Huntington’s Disease (JHD)?
JHD is a rare condition causing mood changes, depression, and involuntary movements (chorea), and while TBZ is used for the treatment of chorea in adults, little is known about safe dosing for children. Moreover, the lack of data available presents a significant challenge for developing treatments for younger patients.
The model development process to answer this QOI involved the following steps:
- Identification of appropriate methods to answer this question based on the resources and expertise available: a population PKPD model was chosen.
- Development of method of choice: Data selection process, model development process and model fitting process. Moreover, identification of where AI tools would be beneficial during these processes.
- Establishment of context of use, regulatory impact, and risk-based analysis on decision consequences
- Development of credibility assessment methods for the selected method of choice to answer this QOI.
The study proposed a TBZ dosing schedule for children aged 2-11 years old; however, the credibility assessment revealed insufficient evidence to support it. The challenges faced provided key insights to build a credibility framework for drug models in orphan and paediatric diseases.
