Kidney stone disease (KSD) is a condition where there are crystal deposits in the kidney, which affects around 10 percent of Canadians. These kidney stones can be painful to pass, and can cause lasting damage to the urinary tract. This places a large burden on the healthcare system and therefore there is motivation to further understand what causes kidney stones and how we can prevent them. The gut microbiome is a community of bacteria living in the gut which can produce substances such as short chain fatty acids (SCFAs). Individuals with KSD have a different makeup of their gut microbiome and lower amounts of these SCFAs compared to healthy individuals. Tributyrin is a supplement which can increase levels of SCFAs. Our data from animal studies indicate that tributyrin supplementation may be able to reduce kidney stone formation. This project aims to understand if tributyrin supplementation helps in prevention or treatment of those with KSD. This pilot clinical trial investigating tributyrin supplementation in individuals with KSD will be conducted in The Stone Centre at Vancouver General Hospital. It will provide a better understanding of the role of the gut microbiome in KSD, as well as explore another avenue of microbiome focused treatments for those with KSD.
Sarah Hanstock is funded for this project by the CANTRAIN-CTTP & Michael Smith Health Research BC Doctoral Studentship 2023 Award Program. This project will be conducted in The Stone Centre at Vancouver General Hospital under the supervision of Dr. Dirk Lange and Dr. Ben Chew. The Stone Centre is a translational research facility which has an international reputation for its care, treatment, and research of kidney stone disease.
Over 13,000 people live with a devastating spinal cord injury (SCI) in British Columbia. People with SCI need specialized care from their family doctors for health issues such as bladder, bowel, skin, pain, blood pressure, fertility, and breathing conditions. However, most family doctors have received little training on how to help a patient with SCI. We will host a Continuing Medical Education event where family doctors and people with SCI can learn about key health issues about SCI and speak freely about their concerns. The Continuing Medical Education content will be developed by doctors with expertise in family practice and spinal cord medicine, as well as by people with SCI who experience these key issues.The event will be broadcast by videoconference and recorded to accommodate people who cannot attend. These activities will complement our existing Spinal Cord Injury Research Evidence (SCIRE) website (scireproject.com) which has a special section for Primary Care and SCI and is accessed by over 300,000 health care providers annually. The Continuing Medical Education event will be posted on our website so that it can continue to be accessed by stakeholders. Lastly, all activities will be evaluated for their impact.
This award is being co-funded by Michael Smith Health Research BC, Genome BC, and Genome Canada.
In Canada, more than 1 in 10 people will suffer a major form of depression at some point in their lives. There are many effective treatments for depression, including drug therapy. Finding a medication that both works and does not cause severe side effects is often a matter of trial-and-error. This may contribute to the high non-adherence rates and, subsequently, to poorer health outcomes and increased costs. An individual’s genetic makeup is thought to be partly related to whether particular drugs work and whether there are side effects with the drug. “Pharmacogenomic” testing, that is, using the patient’s genetic information to determine which particular drug might work best, at the right dose, with the fewest side effects, is a new and promising approach.
In this study, we want to know if pharmacogenomic testing for depression treatment should be routinely used in British Columbia. Through a series of research activities, we will evaluate how much improved health patients might see, as well as whether the testing is good value for money for the health system. As a whole, the project will provide tools for evaluating and addressing societal and economic considerations for the implementation of pharmacogenomics tools into clinical practice.
Dr. Stirling Bryan (Principal Investigator) is a health economist, Professor in UBC’s School of Population and Public Health, a Senior Scientist at the Centre for Clinical Epidemiology and Evaluation (Vancouver Coastal Health Research Institute), and President of the BC Academic Health Science Network. Dr. Jehannine Austin (co-Principal Investigator) is a genetic counsellor, Professor in Psychiatry & Medical Genetics at UBC and executive director of the BC Mental Health and Substance Use Services Research Institute. The remaining multi-disciplinary Canadian team has expertise in health policy research, simulation modeling, systematic reviewing, knowledge translation, and includes patient partners.
End of Award Update – November 2023
Results
Key findings: Our research team synthesized multiple types of evidence and developed a sophisticated simulation model to evaluate health outcomes and costs associated with Pharmacogenomics (PGx)-guided care for adults with major depressive disorder (MDD) compared to usual care. Results indicated a compelling case for PGx implementation; $956M in cost-savings to the health system and large population health gains over 20 years.
Successful and meaningful patient engagement: Three patient research partners joined the team as full, active members of this patient-oriented project early on. The depth and extent of their contribution to all of the research activities benefited the research methods, credibility was enhanced, and other team members reported meaningfulness was added from this engagement.
Several publications: Five high-caliber academic journal publications resulted from this work, including the cost-effectiveness modeling results in the Canadian Medical Association Journal (CMAJ). This led to an invited commentary and press releases from CMAJ and UBC, as well as numerous mainstream news articles and radio interviews. We have three additional manuscripts under review.
Extent of knowledge mobilization: Project activity findings were shared at local, national, and international conferences and seminars with both oral and poster presentations and included patient partner presentations. An array of infographics, lay summaries, and policy briefs were developed, many of which are showcased on our UBC-hosted study website. Two whiteboard animated videos were produced, uploaded to YouTube, and have been viewed more than 800 times.
Impact
In our original grant proposal, we stated that “the project will provide tools for evaluating and addressing societal and economic considerations for the implementation of pharmacogenomics tools into clinical practice”. We achieved this goal throughout the entire project by: 1) Asking people what they think (i.e., interviews with people with lived experience (PWLE), healthcare professionals/providers, and decision-makers); 2) Evaluating what is already known; 3) Analyzing what the BC-specific data show to provide estimates of health service use in a cohort of people with major depression; 4) Putting everything together to evaluate costs and benefits of PGx testing; and 5) Holding an event to share the results with a range of interested/affected groups, as well as an opportunity for them to share their reflections and suggestions.
We produced numerous and widely varied project outputs, which we successfully shared with a range of audiences. This raises awareness of major depression, what kinds of treatments are available, and demonstrates the potential benefit that could be realized by pharmacogenomic testing – a tool that could help practitioners find an effective medication for major depression in a shorter number of medication trials and one that is less likely to cause intolerable or serious side effects. From the patient perspective, this could lead to major improvements in their health and quality of life, without having to undergo what can be a painful, long, and challenging treatment journey to find an effective medication to relieve symptoms of depression. From the healthcare system perspective, this would result in fewer healthcare appointments, hospitalizations, and decrease the use of much more intensive treatments that are also expensive to the healthcare system. Our results provide hope to patients and healthcare providers to guide better medication prescribing for a condition that is extremely common, and yet would benefit from improved treatments.
Potential Influence
The concluding recommendation of the project was to move forward with implementing pharmacogenomic testing for major depression in BC, and we have strong and ongoing policy engagement from the Ministries of Health and Mental Health & Addictions in BC. While our results indicated a compelling case for such implementation (major cost-savings, large population health gains), exploration of implementation strategies, such as which healthcare professionals are best-suited to deliver PGx, is the natural next step and remains unexplored in Canada. We have developed a project proposal for this follow-on phase of work and hope to answer some key questions that remain around implementation.
There has been widespread interest in our cost-effectiveness analysis results, which were published in the Canadian Medical Association Journal. We have had requests to adapt the microsimulation model to other health jurisdictions, so that they are able to establish context-relevant economic evidence for policymakers in those jurisdictions. We very much hope to be able to collaborate with other jurisdictions and remain open to considerations to adapt the model for other interventions for major depression or even for other health conditions.
Next Steps
Our next steps include publishing three further manuscripts (all currently under review), collaborating with other Canadian provinces and other countries to adapt the economic model for those jurisdictions, and to secure funding for the follow-on project around how best to implement pharmacogenomic testing for major depression in BC.
Pharmacogenomic Testing for Major Depression: A Simulation Model
To provide your thoughts on the model described in the video, please contact:
Louisa Edwards, PhD
Research Program Manager
School of Population & Public Health
University of British Columbia
Email: louisa.edwards@ubc.ca
Here is the link to our UBC-hosted project website, which does list publications and some other project outputs (animated videos, conference presentations, infographics): https://spph.ubc.ca/pgx4depression/
