Select Project Abstracts
Genomic and Outcomes Databank for Pharmacogenomic and Implementation Studies (GO PGx)
This Genome Canada project will reduce adverse drug reactions (ADRs) by developing genomic-based precision health strategies and technologies for the most common and severe ADRs in pediatric oncology and facilitate the implementation of pharmacogenomics into clinical practice. This will be realized through four parallel and complementary research activities that will result in genomic-based precision health deliverables for unique end-users:
1. Establish an ADR database of linked clinical and genomic data to discover and validate biomarkers of five severe ADRs associated with cancer therapy drugs in children.
2. Knowledge translation (KT) to facilitate the use of pharmacogenomics in pediatric oncology through the development of clinical practice guidelines and an educational program.
3. Implement ADR-predictive pharmacogenomics tests at 10 pediatric oncology centres across Canada.
4. Exploration of how pharmacogenomics testing in pediatric oncology impacts, and is impacted by patients, families, clinicians, and the Canadian healthcare system (GE3LS – Genomics and its Ethical,Environmental, Economic, Legal, and Social Aspects).
Integrating pediatric pharmacogenomic testing into the Canadian health care system
In collaboration with Dynacare, this project focuses on developing pharmacogenomic tests to predict the risk of experiencing an adverse drug reaction (ADR) in pediatric patients, and strives to bridge the gap between the rigorous science of pharmacogenomics and its integration into health care by providing a tool for the clinical uptake of rigorously derived pharmacogenomic information. To bridge this gap, we have identified actionable pharmacogenomic biomarkers for the most frequently prescribed medication classes and associated ADRs in children: antibiotics, analgesics, and mental health medications. These pharmacogenomic biomarkers all have a compelling rationale for inclusion and were based upon recommendations from FDA and/or Health Canada, Clinical Practice Guidelines, or discovery and replication of research findings in at least three independent populations. Using these robust genomic findings, we will develop three pharmacogenomic panels that possess high analytical validity as well as clinical utility. This product will therefore make the proven benefits of pharmacogenomics accessible to all pediatric patients and their clinicians and pharmacists in Canada. The availability of such tests would provide huge advantages to the thousands of children receiving these frequently prescribed medications every year and will significantly decrease the prevalence of severe and debilitating ADRs related to the most commonly prescribed medications in children.
Optimizing Chronic Hepatitis C Treatment Study
The Optimizing Chronic Hepatitis C Treatment study is investigating the effectiveness and safety of drugs used to treat chronic Hepatitis C Virus (HCV) infection in Canada. Through active surveillance of patients undergoing Hepatitis C treatment in Canadian centres, the project will deliver post-market, real-world safety data in the Canadian population.
This work is in response to questions raised by the Canadian Agency for Drug and Technologies in Health (CADTH) and the Drug Safety and Effectiveness Network (DSEN) regarding the use of genetic and clinical markers to optimize therapy for individuals with HCV. This work is funded by the Canadian Institutes of Health Research (CIHR).
Recent published studies have demonstrated that genetic variants in the IL28B/IFNL4 gene region can accurately predict sustained viral response (SVR). Different genetic variants can also predict ribavirin-induced anemia.
The project aims to investigate the following research questions:
1. Can genetic factors be used to predict each HCV drug regimen’s effectiveness at achieving SVR?
2. Can genetic factors be used to predict in whom serious adverse drug reactions are likely to occur?
3. Can genetic factors be used to predict antiviral resistance?
Detailed clinical and genetic data from patients with HCV infection will be used to develop predictive pharmacogenomic tests to optimize HCV drug therapy selection based on patient risk factors and other clinical criteria. Algorithm-guided HCV therapy is expected to significantly improve HCV treatment response rates by tailoring therapeutic options based on the individual genetic profile of a patient, optimizing response, safety and thereby make treatment most cost effective.
Active surveillance for evaluation of harm of direct acting oral anticoagulants (DOACs) in real-world patients
Oral anticoagulation therapy is the standard therapy for preventing stroke in patients with atrial fibrillation as well as treatment for most cases of deep vein thrombosis and pulmonary embolism. Oral anticoagulation therapy has traditionally involved the use of vitamin K antagonists, most commonly warfarin. However, the narrow therapeutic index combined with need for regular monitoring and slow time to onset have proved challenging in the safe and effective use of warfarin therapy. Due to this, three direct-acting oral anticoagulants (DOACs) have been approved for use in Canada. Similar to warfarin therapy, DOACs have been associated with major bleeding events. There is a need for increased understanding of the safety of DOACs in clinical practice, especially when considering the current lack of antidote for newer therapies.
Active surveillance is necessary to assess the safety of DOACs in real world populations, particularly those not represented in clinical trials that may be more vulnerable to harm. The objective of this project is to conduct active surveillance to determine the safety of DOACs in a Canadian population. Understanding the adverse event profile of DOACs in a real-world population will inform health care practitioners responsible for prescribing DOACs within the ethnically diverse population of Canada and improve the safety of DOAC therapy.
Identifying Clinical Pharmacogenomic Predictors for Antibiotic-associated Severe Cutaneous Adverse Drug Reactions: An International Cohort Pilot Study – BC Children’s Hospital Research Institute Evidence to Innovation Theme Seed Grant Award (2020 – 2021)
Hormonal Contraceptives and Risk of Pseudotumor Cerebri Syndrome in Women of Child Bearing Age – Canadian Institutes of Health Research (2019 – 2021)
Severe Cutaneous Adverse Drug Reactions (SCAR) 2019 International Meeting: From Science to Translation – CIHR Planning and Dissemination Grant (2018 – 2019)
Genomic and Outcomes Databank for Pharmacogenomic and Implementation Studies (GO PGx) – Genome Canada, Genome BC, CIHR Large Scale Applied Research Project Competition: Genomics and Precision Medicine (2018 – 2022)
DSEN SEARCH & PREVENT: active Surveillance and Evaluation of Adverse Reactions in Canadian Healthcare AND Pharmacogenomics of Adverse Reactions EVEnts Nation-wide Team (Renewal) – CIHR Drug Safety and Effectiveness Network (2014 – 2021)
Domperidone to stimulate milk production during lactation and potential risk of serious ventricular arrhythmia and/or sudden cardiac death – CIHR Drug Safety and Effectiveness Network (2018 – 2020)
Integrating pediatric pharmacogenomic testing into the Canadian health care system – Genome Canada Applications Partnership Program (2017 – 2020)
Mitigating cisplatin-induced ototoxicity in childhood cancer treatment through applied pharmacogenomics – Canadian Institutes of Health Research (2017 – 2020)
Preclinical therapeutic development of targeted cardioprotectants for use in cancer patients receiving anthracycline chemotherapy – Canadian Cancer Society (2017 – 2019)
Discovery, validation, and pre-clinical development of novel strategies to prevent anthracycline-induced cardiotoxicity – Canadian Institutes of Health Research (2017 – 2022)
Assessing the Impact of Pharmacogenomic Testing in Pediatric Oncology – Child and Family Research Institute – Evidence to Innovation Seed Grant Funding (2015 – 2016)
Active surveillance for evaluation of harm of direct acting oral anticoagulants (DOACs) in real world patients – CIHR Drug Safety and Effectiveness Network (2015 – 2017)
Clinical and pharmacogenomic predictors of inter-patient variation in direct acting oral anticoagulant (DOAC) plasma concentrations in real-world patients – CHIR Drug Safety and Effectiveness Network (2015 – 2017)
The Drug Safety and Effectiveness Cross-Disciplinary Training (DSECT) program – CIHR Drug Safety and Effectiveness Network Training Grant (2015 – 2020)
Optimizing Chronic Hepatitis C Treatment Using Pharmacogenomic Biomarkers – CIHR Drug Safety and Effectiveness Network (2014 – 2015)
5-HT3 Antagonists (Antiemetics) & Cardiac Safety, Using an Active Surveillance Approach – CIHR Drug Safety and Effectiveness Network (2013 – 2015)
Implementation of A Pharmacogenetic ADR Prevention Program in BC – Genome British Columbia & BC Provincial Health Services Authority (2012 – 2015)