Grant: Team Grant: DSEN Collab Ctre Prospective Studies -Pharmacogenomics of Adverse...

Adverse drug reactions (ADRs) are the 4th leading cause of death and cause an estimated 200,000 severe ADRs each year in Canada. Despite the promise of improved medicines, withdrawals of new drugs (eg. Rezulin, Vioxx) demonstrate the need to identify patients at higher ADR risk. Individual patient variability in drug metabolism genes is a major contributor to the development of severe toxicities, hospitalizations, and deaths from even standard doses of many drugs in clinical use today. To tackle the complex problem of ADRs requires a multi-faceted team to bring together synergistic expertise from scientists and clinicians in many disciplines in an environment that promotes teamwork. Such an undertaking - with the long-term goal of reducing the incidence of severe ADRs - is the vision for the Drug Safety and Effectiveness (DSEN) Pharmacogenomics of Adverse Reaction EVEnts National Team (PREVENT). PREVENT will conduct pioneering and transformative research to identify genetic factors of priority ADRs identified by the DSEN steering committee. In addition to the discovery of novel pharmacogenomic biomarkers, we will leverage our unique abilities to validate their clinical relevance, from cell-based studies to real world patient populations. DSEN-PREVENT cores will consist of a detailed patient clinical characterization core, a pharmacogenomics research core with high-throughput genotyping and sequencing platforms, and a translational pharmacokinetics core with state-of-the-art drug level monitoring facilities. Additional cores will provide capacity for ADR economic assessment and ADR ethical/legal issues. PREVENT will support multiple training centres for clinician-scientists, post-doctoral fellows, and graduate students to train the next generation of leaders in this field. The diverse yet complementary areas of expertise of PREVENT harnesses unique Canadian strengths that will foster innovative research to address the high priority problem of severe ADRs.