Related Experiment Videos
Toxicogenetics in drug development
1Department of Pharmacology and Therapeutics, The University of Liverpool, P.O. Box 147, Ashton Street, L69 3GE, Liverpool, UK. bkpark@liv.ac.uk
Abstract:
The major progress made in the understanding of the genetic basis of inter-individual variation in drug response, alongside the rapid advances in technology, provides major new opportunities to ensure the safe introduction of a new chemical entity into clinical practice. In essence, the aim is to get the right drug into the right patient using knowledge of factors that influence both benefit and risk. The stage of the drug development process at which genetic analysis needs to be undertaken is dependent on the frequency of the event, and the availability of clinical samples. Thus, common adverse events, or assessment of efficacy, will be feasible for testing in phases I-III. However, when a rare event is being studied, for example idiosyncratic toxicity, prospective analysis becomes impossible. Thus, retrospective studies using available drugs is important as it may provide paradigms for future drug development. Additionally, prospective collection of samples will be important so that rare adverse events identified during phase IV can then be analysed using toxicogenetic approaches. Ultimately, information obtained from toxicogenetics must be included in the Specific Product Characteristics (SPC) and thus formally translated into clinical practice in order to contraindicate the drug in specific patients with a genetically determined susceptibility to drug toxicity.
Insights
Leveraging genetic insights and technology advances personalized medicine by matching the right drug to the right patient. Toxicogenetics guides safe drug introduction and clinical practice, improving patient outcomes.
Area of Science:
- Pharmacogenomics
- Drug Development
- Clinical Practice
Background:
- Advances in understanding genetic variation in drug response offer new opportunities for safe drug introduction.
- Personalized medicine aims to optimize drug selection based on individual benefit and risk factors.
Purpose of the Study:
- To explore the integration of genetic analysis into drug development for ensuring safe clinical practice.
- To discuss the strategic timing of genetic analysis based on event frequency and sample availability.
Main Methods:
- Utilizing genetic analysis at various stages of drug development (Phases I-IV).
- Employing retrospective studies for rare adverse events and prospective sample collection for future toxicogenetic analysis.
- Integrating toxicogenetic findings into Specific Product Characteristics (SPC).
Main Results:
- Common adverse events and efficacy can be assessed during Phases I-III.
- Retrospective studies are crucial for understanding rare events like idiosyncratic toxicity.
- Prospective sample collection enables analysis of rare adverse events identified in Phase IV.
Conclusions:
- Toxicogenetics is essential for identifying genetically determined susceptibility to drug toxicity.
- Incorporating toxicogenetic information into SPC is vital for clinical practice and drug safety.
- This approach facilitates the contraindication of drugs in susceptible patient populations, enhancing safety.