Research

The research in our lab focuses on the effectiveness and safety of commonly prescribed medications in vulnerable populations. Vulnerable populations may include many diverse groups of individuals that often exhibit poorer health outcomes. In our studies, we focus on patients with chronic liver disease, older adults, as well as patients subjected to polypharmacy and thus at risk of interactions between different medications. Below follows a brief description of our ongoing research in these three areas.

Prometheus Bound by Peter Paul Rubens

"Prometheus Bound" by Peter Paul Rubens | Source: Wikimedia Commons

Hepatic pharmacoepidemiology

There is a major interplay between pharmacotherapy and the liver. On the one hand, medications can affect liver function, for example through drug-induced liver injury. On the other hand, liver function can affect the metabolism and elimination of medications and thus their effectiveness and safety. However, patients with liver disease are underrepresented or even systematically excluded from randomized trials, the gold standard when it comes to the assessment of drug efficacy. Moreover, randomized trials often lack the necessary sample size to assess the risk of drug-induced liver injury. Therefore, pharmacoepidemiologic studies can provide needed evidence on the hepatotoxic risk of medications and on the effectiveness and safety of medications among patients with underlying liver disease.

To help fill in these important knowledge gaps, we have studied the hepatotoxic risk of a wide range of medications in the past including both prescribed and over-the-counter compounds. Recently, we studied the utilization, effectiveness and safety of direct oral anticoagulants (DOACs) among patients with non-valvular atrial fibrillation and liver disease in a project funded by the Canadian Institutes of Health Research. Currently, our work focuses on the effectiveness and safety of other cardiovascular medications among patients with liver disease and specifically metabolic-dysfunction associated fatty liver disease and liver cirrhosis.

Head of an Old Woman by Peter Paul Rubens

"Head of an Old Woman" by Peter Paul Rubens | Source: National Gallery of Canada

Geriatric pharmacoepidemiology

Older adults have distinct pharmacologic properties compared to younger adults, with changes involving decreased first-pass effect and subsequent drug metabolism due to reductions in liver mass and blood flow. Moreover, the reduction in liver mass combined with the physiological decline in renal function in advanced age can decrease the elimination of several medications. Older adults are also at a higher risk of adverse clinical outcomes and adverse drug effects compared to younger adults. Similar to patients with liver disease, older adults are underrepresented in randomized trials. Hence, pharmacoepidemiologic studies in this age group are indispensable.

Our research in geriatric pharmacoepidemiology focuses on several areas. We assess age-specific drug effects in all of our studies to explore potential effect measure modifications by age. In addition, we have established collaborations with important initiatives and experts in adjacent areas. We collaborate with the Berlin Initiative Study at Charité, an ongoing prospective cohort study among community-dwelling older adults led by Professor Elke Schaeffner. This collaboration focuses on the assessment of the effects of blood pressure, kidney function, and other biomarkers on the risk of adverse clinical outcomes in advanced age. We also collaborate with Professor Paul Brassard at the Department of Medicine at McGill University. This collaboration focuses on the assessment of the effects of common infections and vaccines on the risk of Alzheimer’s disease and other neurodegenerative conditions, thereby using electronic medical records from the United Kingdom.

Image of pills

Image generated by DALL·E, A.I. model developed by OpenAI

Clinical effects of drug-drug interactions

The rising rates of polypharmacy are reflected in an increase in the prevalence of drug-drug interactions (DDIs). DDIs account for >10% of the overall adverse drug effects and up to 5% of hospital admissions among older adults. As a result, they have attracted increasing attention as a modifiable - and for this reason preventable - risk factor of drug toxicity. However, our knowledge about the interaction potential of a given medication is mostly limited to small pharmacokinetic studies conducted among healthy individuals and case reports. Given this important knowledge gap, there is a necessity to conduct pharmacoepidemiologic studies to assess the clinical effects of DDIs.

Our current work in the pharmacoepidemiology of DDIs is diverse. We focus on the effectiveness and safety of interactions involving DOACs by conducting a series of pharmacoepidemiologic studies and also by synthesizing the available evidence in the area through in-depth methodological assessments of previous studies. Moreover, we focus on the application of novel study designs to study DDIs such as the prevalent new-user design. In addition, we explore the potential of spontaneous reports as a tool for hypothesis generation in the area of DDIs as part of an ongoing collaboration with Professor Christopher Gravel at the School of Epidemiology and Public Health at the University of Ottawa. Finally, we are actively involved in the Special Interest Group on DDIs at the International Society for Pharmacoepidemiology.