Concept: Canadian Network for Observational Drug Effect Studies (CNODES)
Last Updated: 2012-12-10
1. Background Information
Prescription drugs constitute by far the most common form of treatment used in clinical practice. In Canada, medication costs have increased over 6-fold during the last 20 years, now representing a significant portion of the total health care budget. Despite the extensive pre-approval studies of safety and effectiveness that drugs are subjected to, it has been estimated that up to 10,000 Canadians die yearly and 150,000 are hospitalized from adverse drug reactions. The need for drug safety and effectiveness research using an epidemiological approach has been clearly recognized for decades and Canada has been a major contributor to this research effort, thanks to the population-based administrative health databases resulting from the Canadian national and provincial universal health insurance programs. While Canadian researchers from different provinces have been individually successful in using these databases to address questions of drug effects, future observational studies will present new challenges that will require larger databases. Indeed, larger sample sizes are needed to estimate effects of low magnitude with high precision, for the study of rare yet serious adverse events, for the study of drugs used by patients with infrequent diseases, and to facilitate the study of medications very early after they enter the Canadian market.
2. Purpose of the Project
The raison d'être of our proposal for the creation of a Canadian Network for Observational Drug Effect Studies (CNODES) is specifically to address this challenge. It will assemble the top pharmacoepidemiologists in the country and use a collaborative, population-based approach, exploiting existing healthcare databases across the country and using sophisticated, cutting edge and powerful analytical methods to rapidly evaluate the risks and benefits of medications on the health of Canadians. The network will also disseminate this information widely to other researchers, clinicians and regulatory bodies; develop and improve the methodology necessary to conduct this research; develop training in the methods and conduct of this research and thus expand capacity in Canada for the population-based study of drug effects.
3. Network Structure
The Network will be structured around a Coordinating Centre and four Teams: Database, Methods, Training and Knowledge Translation.
The Database Team will include all database representatives and be responsible for the development of protocols and conduct of database-specific studies. The databases will include data from the Provinces of British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec, the Maritimes, as well as from the United Kingdom's General Practice Research Database (GPRD). The latter non-Canadian database was included because of its large size, instant online access, and the possibility to study the effects of drugs that have been in use for a longer time in Europe.
The Methods Team will assist the Database Team in issues regarding methods of study design and data analysis for the database-specific protocols and be responsible for the meta-analytic pooling of findings from each database. It will also work on the evaluation of existing methods and the development of new methods of study design, data analysis and techniques of meta-analysis for pooling studies.
The Training Team will organize training activities in the design and analysis of database studies for members of the Network and decision-makers. These will encompass courses, seminars and special lectures in this field, making use of newer interactive multimedia technologies.
The Knowledge Translation Team will serve to bring researchers and research-users together to ensure that the research conducted addresses identified information gaps and is disseminated to relevant decision makers and stakeholders.4. Project Activities
In the first year of this 5-year grant, the Network will assess its capabilities by conducting two demonstration projects. The first study will assess the risk of acute kidney injury associated with the use of statins at high-doses. The second study will determine whether proton-pump inhibitors (PPIs) increase the risk of severe community-acquired pneumonia. With the contradictory nature of the evidence for these two drug effects, the CNODES is well-placed to address these questions, of particular significance given the large and growing number of Canadians being prescribed statins and PPIs. Cohort studies will be performed within each database according to a common protocol, with analyses providing database-specific estimates of the rate ratios of these two outcomes associated with high-potency statin use or PPI use. The results from participating centers will be pooled using meta-analytic techniques to provide unique risk estimates.
While the first year of the grant will be used to set up and test the network infrastructure via these two projects, the subsequent years will be dedicated to addressing questions of importance to Canadian public health.5. Project Outcomes
The creation of the Canada-wide CNODES, uniting the top pharmacoepidemiologists in the country with access to data on over 27 million people, will thus provide a powerful tool to rapidly evaluate the risks and benefits of medications used by Canadians. It will also facilitate the wide dissemination of this information to all stakeholders, including clinicians, patients and decision makers.