Adverse drug reaction active surveillance: developing a national network in Canada's children's hospitals.
OBJECTIVE
Adverse drug reactions (ADRs) rank as the fifth leading cause of death in the western world. The nature and scope of these ADRs in children are not predictable based on post market surveillance reports that rely heavily on adult drug experience. The genotype-specific approaches to therapy in childhood (GATC) national ADR network was established to identify specific ADRs and to improve drug safety through identification of predictive genomic biomarkers of drug risk.


METHODS
GATC set out to establish a national network of trained surveillance clinicians in pediatric hospitals across Canada. Surveillance clinicians identified, enrolled, and collected clinical data and biological samples from ADR cases and controls. Surveillance was targeted to three ADRs: anthracycline-induced cardiotoxicity, cisplatin-induced hearing impairment, and codeine-induced mortality in breastfed infants.


RESULTS
The initial surveillance site was established in September 2005, with 10 sites fully operational by 2008. In 3 years, GATC enrolled 1836 ADR cases and 13188 controls. Target numbers were achieved for anthracycline-induced cardiotoxicity. Modified target numbers were nearly attained for cisplatin-induced hearing impairment. Codeine-induced infant mortality in a breastfed infant was discovered by GATC investigators. A case-control study was subsequently conducted.


CONCLUSIONS
GATC has demonstrated a model of active and targeted surveillance that builds an important step toward the goal of personalized medicine for children. Effective communication, site-specific solutions and long-term sustainability across the network are critical to maintain participation and productivity. GATC may provide a framework of ADR surveillance that can be adapted by other countries and healthcare systems.
Carleton
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Pharmaceutical Outcomes Programme, Children's and Women's Health Centre of British Columbia, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada. bcarleton@popi.ubc.ca
Poole
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Smith
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Leeder
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Ghannadan
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Ross
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Phillips
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Hayden
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D016907:Adverse Drug Reaction Reporting Systems / Q000458:organization & administration*; D000701:Analgesics, Opioid / Q000506:poisoning; D018943:Anthracyclines / Q000009:adverse effects; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D001942:Breast Feeding; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D002662:Child Health Services / Q000458:organization & administration*; D002675:Child, Preschool; D002945:Cisplatin / Q000009:adverse effects; D003061:Codeine / Q000506:poisoning; D062787:Drug Overdose / Q000235:genetics / Q000401:mortality; D005260:Female; D005819:Genetic Markers; D034381:Hearing Loss / Q000139:chemically induced; D006331:Heart Diseases / Q000139:chemically induced; D006776:Hospitals, Pediatric / Q000458:organization & administration*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009313:National Health Programs / Q000458:organization & administration*; D010597:Pharmacogenetics; D016730:Program Development; D013997:Time Factors
D000701:Analgesics, Opioid; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D005819:Genetic Markers; D002945:Cisplatin; D003061:Codeine