Flory Muanda
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Assistant Professor BSc in Medicine, University of Kinshasa Office: Medical Sciences Building, 287
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Why Science?
Born in Belgium to a pharmacist father and a speech therapist mother, I grew up in Kinshasa (RD Congo) in a neighborhood designed for University of Kinshasa faculty members and their families.
When I started medical school, I developed a passion for research. As a result, I fell in love with physiology and pharmacology classes. I was fascinated by how medications could be delivered to the human body and act at a molecular level. After completing medical school, I spent two years in a residency program in internal medicine but switched to clinical pharmacology after a joint department was created between the medical school and pharmacy school at the University of Kinshasa. My interest in applied research was sparked during that time while I worked as a clinical investigator on many malaria-randomized clinical trials.
In 2011, I moved to Montreal to complete a PhD in Pharmacoepidemiology with Dr. Anick Bérard (a world-renowned researcher in the field of drug safety in pregnancy) at the Faculty of Pharmacy of the University of Montréal. As pregnant women are excluded from clinical trials, high-quality evidence is lacking for managing maternal infections in pregnant women. Therefore, I conducted population-based studies using routinely collected healthcare data to inform safe antibiotic prescribing in pregnancy. Following my Ph.D., I moved to London and joined the ICES Provincial Kidney, Dialysis and Transplantation Program (ICES KDT) and the Department of Epidemiology and Biostatistics at Western University as a research fellow working with Dr. Amit Garg. During my time at ICES KDT, my research program aimed to reduce medication errors in patients with low kidney function. I conducted population-based studies to inform safer prescribing practices for older adults with chronic kidney disease using routinely collected healthcare data in Ontario (one of the few jurisdictions worldwide with linked population-based kidney lab data). After my postdoctoral fellowship, I was recruited to Western University as an Assistant Professor and joined the Department of Physiology and Pharmacology.
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.
Most Rewarding Moments
One of the most rewarding moments in my early career was when in 2018, one of my PhD manuscripts won the prize for the best paper published in the British Journal of Clinical Pharmacology for quantifying the risk of major congenital malformation associated with the gestational use of antibiotics. The findings of this study have contributed to improving the treatment of maternal infections during early pregnancy. As part of my postdoctoral fellowship, I studied the safety of baclofen in renal patients, a popular muscle relaxant with renal elimination. I have shown that baclofen initiation was associated with significant harm in renal patients. These results contributed to updating the safety medication list developed by the Ontario Renal Network and distributed to healthcare providers and patients to increase awareness and avoid medication incidents. Our study results have also been cited in the clinical decision support tool, which more than 1.9 million clinicians use in 190+ countries.
Advice to Students:
One advice for students is to remain persistent and determined, regardless of circumstances. In most cases, success is proportional to effort.
Interests Outside of Academia:
I spend quality time with my family and friends, watch TV shows, and go for a walk. I have developed a passion for cooking as well.
| 2019 | Postdoctoral Fellowship award, MITACS |
| 2019 | Postdoctoral Fellowship award, Canadian Institutes of Health Research |
| 2018 | British Journal of Clinical Pharmacology, Prize for young investigators (best paper published) |
| 2018 | Dean's Honours List for PhD thesis (University of Montréal) |
Publications:
See my publications on PubMed
- Muanda FT*, Weir MA, Bathini L, Blake PG, Chauvin K, Dixon SN, McArthur E, Sontrop JM, Moist L, Garg AX. (2019). Association of Baclofen with Encephalopathy in Patients with Chronic Kidney Disease.JAMA.322(20): 1987-1995. [Impact Factor 157.3]
- Kianna J Chauvin, Peter G Blake, Amit X Garg, Matthew A Weir, Lavanya Bathini, Stephanie N Dixon, Eric McArthur, Jessica M Sontrop, Louise Moist, Richard B Kim, Flory T Muanda*. Baclofen has a risk of encephalopathy in older adults receiving dialysis [published online ahead of print, 2020 May 22]. Kidney Int. 2020; S0085-2538(20)30552-4. [Impact Factor 18.9]
- Muanda FT*, Sood MM, Weir MA, Sontrop JM, Ahmadi F, Yoo E, Kim RB, Silverman MS, Knoll GA, Garg AX. Association of higher-dose fluoroquinolone with serious adverse events in older adults with advanced chronic kidney disease. JAMA Netw Open 2022 Aug 1;5(8):e2224892.doi: 10.1001/jamanetworkopen.2022.24892.
- Muanda FT*, Weir MA, Ahmadi F, Sontrop JM, Cohan A, Fleet J, Blake PG, Garg AX (in press). Higher-Dose Gabapentinoids and the Risk of Adverse Events in Older Adults With CKD: A Population-Based Cohort Study. Am J Kidney Dis. 2021. [Impact Factor 11.0].
- Muanda FT*, Weir MA, Bathini L, Clemens KK, Perkovic V, Sood MM, McArthur E, Sontrop JM, Kim RB, Garg AX. Higher-Dose Sitagliptin and the Risk of Congestive Heart Failure in Older Adults with CKD. Clin J Am Soc Nephrol. 2020 Dec 7;15(12):1728-1739. doi: 10.2215/CJN.08310520. Epub 2020 November 25. PMID: 33239410; PMCID: PMC7769019
