13. Statistical aspects of animal to human translation

Team: Dr Richardus Vonk (Bayer), Dr Thomas Jaki (Lancaster University)
Clinical Advisor: Prof Damian O’Connell, head of Clinical Sciences at Bayer and former professor for molecular medicine at University College Cork.
Location: Bayer Pharma AG (Berlin, Germany)

Translational sciences are currently moving into the focus of applied pharmaceutical research. The high costs and long duration of clinical development, paired with high levels of attrition, require the quantification of the (un)certainty when moving from preclinical animal research to clinical development.

Recent publications^6,23 bemoan the lack of reproducibility of preclinical research. Results from preclinical animal studies tend to be available from multiple species, and estimate potential effects with different levels of variability. Even for well-designed experiments with reproducible results the translation from animal to man is a key challenge. In this project, statistical methods incorporating results from animal models in the design of early clinical trials will be developed.

Specifically methods to derive prior distributions from preclinical research for efficacy or safety assessments in early clinical development will be investigated. Together with first data in humans, these distributions may be used for proof of concept decisions. Translating pre-clinical biomarker findings into early clinical development of biomarkers is crucial. These findings may be related to safety and/or efficacy in early clinical development. Further to the translational aspects from animal studies to human studies, here also meta-analytical approaches which incorporate results from other compounds in the same class could be applied. The investigations into statistical methodology could cover a wide range of concepts. Without being complete, some of these are Bayesian approaches, adaptive designs and meta-analytical methods.

Meet our Early Stage Researcher: Eleni Vradi, Bayer Pharma AG

I completed my undergraduate studies in Mathematics and further studied towards an MSc in Applied Statistics in AUEB, Greece. In my master thesis I worked on genetical statistics. Since 2012, I have been with the Mathematics Department at University of Copenhagen where I specialized in Theoretical Statistics, with a thesis on modelling environmental effects for family data. During a three-year employment at the Department of Biostatistics in Copenhagen, I worked within the fields of survival analysis and epidemiology, with emphasis in registry-based studies. My main research interest during my PhD will be translational science, focusing on statistical methods to translate pre-clinical results into the design of early clinical studies.

⁶ Freidlin B, Korn EL. (2014) Biomarker enrichment strategies: matching trial design to biomarker credentials. Nat Rev Clin Oncol 11, 81–90.

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