Every year, 150,000 Canadians are hospitalized and 10,000 die from adverse reactions to prescription drugs. This may sound shocking for a country with a rigorous drug approval procedure. But the fact is that no clinical trials of the safety and efficacy of novel therapies can possibly foresee all the variable comorbidities and interactions with other medications to be encountered in real world use. These include long-term effects that only appear after a drug has been consumed by many people over years.
Five years ago, the Canadian Network for Observational Drug Effect Studies (CNODES) was launched as a national collaboration of researchers to monitor after-market drug safety and effectiveness. Its achievements, under the leadership of Dr. Samy Suissa, Director of the Centre for Clinical Epidemiology, convinced the Canadian Institutes for Health Research (CIHR) to renew its mandate for another five year term.
“Our team has exceeded all expectations ,” said Dr. Suissa. “By pooling the expertise of some of the best minds in Canadian pharmacoepidemiology, we have optimized the quality and quantity of research we can accomplish. We have substantially improved the study of drug safety and effectiveness by our ability to access and mine big databases.”
CNODES studies questions posed by Health Canada and the Canadian Agency for Drugs and Technologies in Health (CADTH). Its findings have been published in high impact journals and have attracted a worldwide audience among clinicians and regulators.
“We have answered some very important questions with regard to commonly used medications for cardiovascular disease, diabetes, Parkinson’s disease, gastrointestinal conditions, and others,” Dr. Suissa points out. “Our work has had a direct impact on clinical practice.” One example he cites is the case of isotretinoin. A popular and effective acne medication, it can lead to malformed fetuses when given during pregnancy. Consequently, using data from across Canada, CNODES reported that such improper usage still occurs and reminded clinicians against its prescription to women at risk of becoming pregnant.
Asked to identify results he found surprising, Dr. Suissa referred to the proton-pump inhibitor (PPI) study led by Dr. Kristian Filion, an investigator in the LDI’s Centre for Clinical Epidemiology, that contradicted many previous findings that the use of these drugs was associated with a heightened risk for pneumonia. Since most patients using PPI are elderly, the danger of contracting pneumonia is especially severe. Debunking this side effect allows doctors to prescribe this very effective gastrointestinal reflux medication with greater confidence.
As compared with pre-approval clinical trials that engage hundreds of patients, CNODES has access to medical records of more than 102 million people in databases from Canada, the United Kingdom, and United States. Moreover, it is creating new methodologies for biostatistical and epidemiological analysis. One innovation being piloted is to employ real time monitoring of data so that, in addition to historical records, researchers can observe effects as they occur. A rapid response unit has been created to react quickly in the event of an urgent public health issue.
Other investigators from the LDI’s Centre for Clinical Epidemiology actively involved in CNODES research include Drs Pierre Ernst, Laurent Azoulay and Christel Renoux. Forthcoming studies include the new anticoagulants being employed against venous thromboembolism and atrial fibrillation; new biologic agents to treat rheumatoid arthritis; and quetiapine, an antipsychotic used to treat schizophrenia, bipolar disorder and major depressive disorder.
CNODES major highlights: the first five years:
· High potency statins and the risk of acute kidney injury – BMJ
· PPIs and the risk of community acquired pneumonia – Gut
· High potency statins and the risk of diabetes – BMJ
· Incretin-based therapies and pancreatic cancer – BMJ
· Isotretinoin use in pregnancy – CMAJ
· Domperidone use and sudden cardiac death in Parkinson's disease— British Journal of Clinical Pharmacology
· Incretin- based therapies and the risk of heart failure – New England Journal of Medicine
· Incretin-based therapies and the risk of pancreatitis – JAMA Internal Medicine