$25 billion +
Typically, a drug trial will involve a few thousand carefully selected individuals to test for safety and effectiveness. However, once a medication has been on the market for years and prescribed to tens or hundreds of thousands of patients, unanticipated effects may become observable. Using extensive databases and sophisticated analyses, researchers illuminate those sometimes difficult to discern interactions that beg caution.
Uncovering unexpected side effects and unanticipated benefits from existing treatments are the work of researchers at the Centre for Clinical Epidemiology.
“It is essential for public health that we check the long-term effects of the drugs we prescribe,” said Dr. Laurent Azoulay, a pharmaco-epidemiologist at the LDI. “Studying large databases of patients is the best way to draw a clear picture of risks and rewards so that we can constantly improve standards of care.”
Although all medical therapies are subjected to a lengthy and rigorous approval process that includes carefully randomized controlled clinical trials before being made available to humans, some effects can only become known after they have been used over a long time and by larger populations than could ever be incorporated in a trial. For example, a rare effect that is exhibited in one out of 100,000 cases is not likely to be observed even in a large clinical trial in which several thousand people participate. Thus, it is essential that therapies be re-evaluated until it is evident that all their properties are revealed. This process requires meticulous attention to the design of the study and necessitates the use of highly sophisticated analyses that incorporate a broad range of variables to be calculated. Since not all variables are necessarily recorded in a single database, researchers must create links across different databases. It is a time consuming process, in which the LDI is doing pioneering work that requires finding the appropriate data, evaluating its accuracy, and then applying it to the specific questions at issue.
“Every drug carries certain risks and it is our duty to identify and quantify them in order to improve the safety of patients,” Dr. Azoulay went on. “Our work provides much needed information on the short- and long-term effects of drugs, which can help physicians and patients properly weigh the benefits of a treatment against its possible risks.”
A recent finding by Dr. Azoulay was that pioglitazone, a drug commonly prescribed to treat type 2 diabetes, doubles the risk of bladder cancer after more than two years of daily exposure. And, while the overall risk remained low, it is important that it be recognized when doctors and their patients assess the use of this particular therapy.
“Beyond this, as we are looking to improve outcomes for cancer patients, we look to existing drugs that have proven to be safe when taken over a long time,” he said. “If there is a drug out there that is associated with improved survival, we need to understand it so that we can employ the drug to this effect. It is demonstrably faster to get such a drug to patients than it would be to develop and test an entirely new compound.”
Metformin, a safe and widely used drug that controls diabetes, exhibited some anti-cancer properties in the lab that were interesting enough for researchers to seek verification among a large population of patients who were using it. Because of the desperate need for novel cancer therapies, it was important to follow up on the possibility that metformin might be effective as quickly as possible. An in-depth epidemiological analysis is much more efficient than setting up a specific randomized clinical study.
“Our ability to provide the public, regulatory agencies, and physicians with cost-effective answers on important issues helps to ensure the safety of the treatments we prescribe,” he said, “as well as revealing potential new applications for those treatments we know to be safe and effective.”
Epidemiology Research Axis / Centre for Clinical Epidemiology (CCE)
The Epidemiology Research Axis, under the direction of Dr. Samy Suissa (an internationally recognized scientist in the field of pharmacoepidemiology), applies cutting-edge epidemiological methods to study the etiology, diagnosis, treatment and prognosis of disease. Researchers also contribute to the improvement and innovation of epidemiological and statistical methods necessary for the rigorous conduct of this research, and are credited with over 100 publications per year, including many in top-ranking clinical and methodological journals. Its activities apply directly to clinical practice and cut across numerous disciplines.
The Axis is home to the Centre for Clinical Epidemiology (CCE), which was founded in 1992 as part of the creation of the network of Clinical Epidemiology units instituted across all McGill teaching hospitals. The CCE conducts epidemiological studies that incorporate vast amounts of data to assess drug safety and the effectiveness of various treatments in order to improve clinical practice and health care. Members of the CEE carry out multidisciplinary research that assesses the distribution and determinants of human illness with the aim of establishing reasoned preventive measures.
Major areas of research include the causes of disease, disease outbreak investigations, disease surveillance and screening, bio-monitoring (analysis of exposure to environmental chemicals for health risk assessment), and comparisons of treatment effects. Since it was founded in 1991, the CCE has established itself as a leader in pharmacoepidemiology (study on the use of, and the effects of, drugs in large patient populations), randomized clinical trials (used to test the efficacy and/or effectiveness of various types of medical interventions, as well as to gather useful information about possible adverse effects), neuroepidemiology, health services research, cardiovascular epidemiology, epidemiology of thromboembolic disorders (blood clots), geriatrics, and emergency medicine.
In 2011, the LDI and CEE became the national headquarters for the Canadian Network for Observational Drug Effect Studies (CNODES), a major research initiative in which scientists from across Canada have joined forces to assess the safety of prescription drugs. CNODES is harnessing the expertise of leading pharmacoepidemiologists to analyze digitized data concerning the experiences of more than 27 million Canadians with their medications. The goal is to determine whether any adverse effects are revealed after a drug has been on the market and used by far greater, and more varied, groups of patients than could ever be accounted for in a clinical trial setting.
Support the work of Drs. Azoulay and Suissa and their fellow researchers in the Epidemiology Research Axis in the Lady Davis Institute and contribute to the continuous improvement of clinical practice and standards of care.