Research Goals

My research goal is to improve prescription-drug safety and effectiveness for older adults.  In 2022, over 7 million Canadians were aged 65 or older, representing 18.8 % of Canada's population. By 2030, over 9.5 million Canadians will be 65+, representing 23% of Canadians (~1 in 4 Canadians).

 

Older adults are at particular risk. More than 90% of non-institutionalized adults older than 65 years take at least one medication, and 80% take multiple medications. One in six hospitalizations among older adults are for adverse drug events. These events have a tremendous negative impact on patients and generate substantial healthcare costs. Common adverse outcomes include falls, hypotension, delirium, and heart failure. In 2013, approximately 1 in 3 older adults in Canada filled potentially inappropriate prescriptions with an estimated cost to the healthcare system of $419 million.

 

In Canada and worldwide, there are significant gaps in information on the safety and effectiveness of drugs used in real-world settings, especially among older adults who are usually excluded from randomized controlled trials.

 

To achieve this goal, I have designed a research program that will leverage routinely collected healthcare data held in databases at ICES (ices.on.ca). These databases are well-suited for conducting post-market drug-safety studies in older adults: They contain encrypted data on healthcare visits, hospitalizations, and lab tests for all Ontario residents and the prescription records of ~2.2 million Ontarians aged 65+.

My lab conducts population-based studies to study the adverse effects of drugs prescribed in routine care using large healthcare databases in Ontario. we use appropriate study designs for drug safety research (cohort study, interrupted time series analysis) to answer clinically relevant research questions. To control for confounding by indication, my lab uses active comparators (when available) and advanced statistical analyses (such as propensity score matching and propensity score weighting) to balance baseline characteristics between the group of comparisons. To ensure the accuracy and robustness of our findings, my lab conducts multiple sensitivity analyses (E-value, negative control exposure, negative control outcome).

 

Specific Research Interests

 

1. The real-world use and outcomes of renally and non-renally cleared drugs commonly prescribed to older adults with chronic kidney disease.

Medications with renal excretion can accumulate in the blood in patients with chronic kidney disease. To prevent toxicity, the product monograph and dosing guidelines recommend dose adjustments or contraindications of these medications in these high-risk patients.

My lab studies the safety of renal elimination medications in older adults with low kidney function. We also examine the safety of medications that are not eliminated by the kidneys and medications prescribed to dialysis patients.

 

2. The real-world use and outcomes of hepatically cleared drugs commonly prescribed to older adults with chronic liver disease.

Approximately one-third of older adults have chronic liver disease in Canada. Medication with hepatic metabolism is often dose-reduced in these patients to avoid toxicity; however, information about optimal dosing, safety, and effectiveness is often lacking.

To fill this research gap, my lab examines medication safety in liver dysfunction patients. Additionally, we investigate whether the severity of liver disease (i.e., chronic liver disease with and without cirrhosis) may influence exposure-outcome associations.

 

3. Drug-drug interactions in older adults.

Information on drug-drug interactions comes from small pharmacokinetic studies and case reports. Over 80% of older adults take multiple medications. Yet, drug-drug interaction is understudied in this high-risk population in real-world settings.

To fill this research gap, my lab conducts population-based studies to examine the consequences of drug interactions in older adults receiving multiple medications. Furthermore, we investigate whether kidney function and liver function influence exposure-outcome associations.

 

4. The effectiveness of commonly prescribed drugs in high-risk older adults using a target trial emulation design when a randomized trial is not available.

The approval process for prescription drugs is largely based on data from clinical trials that study a limited number of patients under highly controlled conditions. Older high-risk patients are typically underrepresented in these trials.

My lab uses routinely collected data in Ontario to emulate a target trial when a randomized trial is not available to inform the effectiveness of medications in older adults, including those with chronic kidney and liver disease.

 

5. High-throughput computing to accelerate post-market drug surveillance.

The traditional approach to conducting post-market drug surveillance has limitations. Each study examines only 1 or 2 drugs and only a few outcomes. With this approach, many harmful effects are missed, and small knowledge gains take years to achieve.

To advance the field, my lab collaborates with computer scientists, clinicians, and biostatisticians at Western to develop high-throughput computing methods to detect unsafe prescribing practices.

 

6. Conduct collaborative research with the Department of Physiology and Pharmacology and beyond

My lab plans to develop collaborative research with department members to (i) replicate findings from laboratory experiments in a real-world setting using administrative healthcare databases and (ii) replicate findings from population-based studies using administrative healthcare databases in animal and in vitro models.