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The following column was provided to Hospital News by Dr. David Hill, scientific director, Lawson Health Research Institute. 

Dedicated health researchers across the country are working every day to make discoveries that improve patient outcomes and support a higher quality of life. Our research hospitals have a mandate to develop and test new treatments, technologies and procedures that address our most pressing health challenges.

There is a cycle of health innovation that is supposed to happen – scientific discoveries are made, they transition to clinical trials and then are adopted as an improved standard of care. This is followed by evaluations of the new method and moving along to the next cycle of refinements and improvements. But the reality in Canada is that gaps, in some cases chasms, disrupt the creation and adoption of evidence-based health innovations.

This starts with discovery. The research funding climate in Canada continues to be extremely difficult. Despite the Federal Government outlining substantial new investments in discovery research in Budget 2018 much of that money will not be available to researchers until 2020 and beyond, and the Canadian Institutes of Health Research (CIHR) continues to be limited by a low funding rate of around 14 per cent. Funding for large, definitive clinical trials is especially difficult to support with public funds. Too many good ideas are left unfunded, and in that environment researchers can feel it’s wiser to propose incremental and ‘safe’ science that avoids controversy and the risk of losing support for experienced research teams built up over many years.

Yet researchers are persistent and manage to secure funding from a range of smaller agencies. Unfortunately, many of these do not fund the indirect costs of research necessary to cover administration, infrastructure, equipment maintenance and upgrades, and the investigator’s salaries. Indirect costs are estimated to be approximately 40 per cent on top of direct study costs. In research hospitals these costs generally fall on the institutions to find funding outside of the provincial government budget that covers the costs of hospital care. This is a negative spiral whereby the more successful a hospital becomes in attracting research funds, the bigger the gap in finding the resources to support that research.

When innovative solutions to health care problems are delivered, backed by solid evidence, adoption into our hospital-based care is often far from rapid. Currently, in most provinces, there is no funding mechanism to translate health innovation to the ‘real world’ setting of our front-line care. Yet, such a mechanism is crucial to the translation of science. Clinical trials are carefully designed with strict protocols and criteria for a highly specific population of patients. Innovations that work in a clinical trial do not always work in the real world where patient populations and settings are much more complex.

Following a clinical trial, innovation needs to be tested at the point of care. Without funding to do this, research innovation hits a roadblock. Scientists are left waiting and hoping that one day their provincial government might look to incorporating their innovations into the health system funding schedule. Meanwhile, their work may be used to inform health care improvements in other nations.

An example can be found in medical imaging research. Canadian scientists, including those at Lawson Health Research Institute, are leaders in the development of positron emission tomography (PET) biomarkers to improve diagnosis and understanding of disease using PET scans.  PET biomarkers are successfully created and then validated in clinical trials across our nation, but there is little funding to translate them back in a timely fashion to patient care in our hospitals. While countries like the US and Europe readily adopt these innovations, Canada lags behind.

This gap was addressed in a report to the Federal government by the Advisory Panel on Healthcare Innovation entitled “Unleashing Innovation: Excellent Healthcare for Canada” and published in 2015. The panel recommended the formation of a Healthcare Innovation Agency of Canada open to hospitals and other care providers in order to evaluate health innovations in the real-world setting of our health system. Scientists would apply by putting forward evidence from their research, including that collected from clinical trials. They would then design a new translational study to test their innovation at the point of care, with the goal of building evidence for presentation to provincial government.

Will everything tested at the point of care succeed? No; some things will fail in the real world. This is why such a fund is so important. It will show whether or not an innovation truly benefits patients and if it’s ready for wider adoption. If successful, the evidence will highlight the right time to bring innovations into the mainstream standard of care. By bridging this gap in the system, we can improve patient care and ensure a timely return on the investment in science.

Dr. David Hill is scientific director at Lawson Health Research Institute, the research institute of London Health Sciences Centre and St. Joseph’s Health Care London.

For Wayne Kristoff, the possibility of getting off all medication for his type 2 diabetes was so intriguing he jumped at a chance to participate in an innovative trial in London. The REMIT study aims to induce remission of the condition – an exciting new concept being tested by researchers at Lawson Health Research Institute.

Kristoff was diagnosed in June 2014, which was difficult but not unexpected because there is a history of the illness in his family. He had to work his way up to taking four pills a day for his diabetes, which came with significant side effects. “If there was a way to get off medication, I wanted to be part of it,” says the 68 year-old. 

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He met the study criteria and was enrolled in February 2016. The results, so far, have been life changing for the Londoner. Since May 2016 Kristoff (right) has been off all medication, his blood sugar levels are good, and he has more energy and feels better than he has in years. He’s also lost 30 pounds thanks to the support offered by the research team.

“I remember well where I was and what I was doing when I received the call telling me that I could stop taking all of my diabetic medication,” adds Kristoff.

A second REMIT trial is now being launched, providing another opportunity for individuals with type 2 diabetes to take part. The trial challenges traditional type 2 diabetes treatment by testing an aggressive approach in recently diagnosed patients. St. Joseph’s Hospital in London is one of seven Canadian sites taking part in the landmark REMIT study. Being led by the Population Health Research Institute (PHRI), a joint institute of McMaster University and Hamilton Health Sciences, the trial follows a PHRI pilot study of early aggressive treatment that resulted in up to 40 per cent of 83 patients with type 2 diabetes going into remission and not needing any diabetes treatment for at least three months.

When Lawson launched the initial trial in December 2015, it generated a surge of interest with more than 200 people with type 2 diabetes asking to participate.

“The idea of remission in type 2 diabetes is obviously captivating to both patients and clinicians,” says Lawson researcher and endocrinologist Dr. Irene Hramiak, Chief of the Centre for Diabetes, Endocrinology and Metabolism at St. Joseph’s. “This overwhelming interest in the REMIT trial tells me that patients want solutions that will optimize care and reduce the complications associated with this disease.”

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Twenty-seven patients met the criteria and are enrolled in the first REMIT trial at St. Joseph’s, which is ongoing, says Dr. Hramiak (left). For the second trial, 20 to 25 patients are being sought who have been diagnosed with type 2 diabetes in the past five years. Some research participants who came forward for the first trial have been enrolled in the second. Each trial is testing a different combination of drugs. For both trials, patients are randomized to receive either the experimental treatment or the standard treatment. In addition, both groups are supported to make lifestyle changes to enhance control of their diabetes.  

The standard treatment for people diagnosed with type 2 diabetes is to start on a single medication, which is then followed by the addition of more drugs and insulin as the disease progresses, explains Dr. Hramiak. In the REMIT study, patients undergo an experimental intensive treatment - two diabetes oral medications plus insulin at bedtime - for three months to see if remission can be induced and how long patients can go without any medication.

“By being proactive with aggressive treatment early on, the theory is that we may slow the progression of the disease,” says Dr. Hramiak. “We are attempting to actually change the disease and induce remission, which is a significant departure from the current approach.”

Those who would like more information about the trial can call 519 646-6100 ext. 65373.

The Canadian Cancer Society (CCS) is uniting with a team of 12 researchers and collaborators to lead one of the world’s largest randomized controlled clinical trials using fecal microbiota transplantation (FMT) to improve the effectiveness of the standard of care for advanced melanoma. This phase II trial is made possible by investments of $1 million each from CCS and the Weston Family Foundation and will be overseen by the Canadian Cancer Trials Group. 

An estimated 11,300 Canadians are expected to be diagnosed with melanoma in 2024. The current standard of care for patients with advanced melanoma is a type of immunotherapy called immune checkpoint blockade (ICB) and while it plays an important role in treatment, more than half of patients will still experience disease progression and unfortunately die of the disease. Finding a path to make this treatment effective for more people would have enormous impact on patient care and significantly improve the odds of surviving advanced melanoma. 

The funding from CCS and the Weston Family Foundation supports all translational research and part of the trial costs (study ME17). The study is being co-led by researchers from Université de Montréal's affiliated hospital research centre (CRCHUM) and Lawson Health Research Institute, alongside collaborators and close to 130 patients with advanced melanoma who will be recruited throughout Canada to participate in this study.

The phase II trial builds on previous research that also received funding support from CCS. Those studies showed the safety and therapeutic potential of using healthy donors’ stool to influence a patient’s gut microbiota and make treatment for advanced melanoma more effective. The study will administer fecal microbiota transplants using specially-prepared oral capsules produced and pioneered at Lawson Health Research Institute, which have been a game changer in patient acceptance and ease of use.

For the past five years, the Weston Family Foundation has supported Canadian researchers working to leverage the microbiome to improve cancer diagnostics, therapy and patient care. 

The biggest and most critical issues related to cancer, such as improving treatment effectiveness for people living with melanoma, are issues that require collaboration. From researchers to clinical trial leaders, to academic and scientific institutions, to caring funders and generous donors, it takes a society to transform cancer. To support cancer research and clinical trials, visit cancer.ca.

Quotes

“What saved me was trusting the scientists who knew what they were doing and the promising results of the clinical trial. To someone who is diagnosed, I would say that if you are offered this treatment, it may sound strange, but it is to help you. Thank you to the partners and the CRCHUM team for their support and for the treatments that went wonderfully well and saved my life." - Louise-Hélène Giroux, diagnosed in 2021 with stage 4 melanoma, first patient in the phase I clinical trial in Quebec to try FMT treatment 

“Because of the generosity of our donors, we are able to invest in world-leading cancer research and clinical trials like this trial focused on advanced melanoma. In 2020, together with the Lotte and John Hecht Memorial Foundation, we committed nearly $1.5M into this research through an Impact Grant. Today, we are joining with the Weston Family Foundation to double down on our original investment through this clinical trial because we believe this work will transform the future of melanoma, saving lives and bringing hope to thousands of people facing the disease every year in this country.” – Dr. Stuart Edmonds, Executive Vice President, Mission, Research and Advocacy, Canadian Cancer Society

“The Weston Family Foundation is thrilled to support this pioneering research into the role of the microbiome in the fight against cancer, which has real potential to transform treatments and care for this devastating disease. It's a bold step forward in our mission to invest in innovation that delivers measurable impacts to the well-being of Canadians. Working alongside forward-thinking researchers and partners like the Canadian Cancer Society will make way for advancements that help to bring hope to patients and families affected by melanoma.” – Garfield Mitchell, Chair, Weston Family Foundation  

 “We are aiming to safely change the patient’s gut microbiota to improve the benefit of immunotherapy in several cancers, including melanoma. This experimental treatment consists of transplanting stool from healthy donors using a Health Canada-approved process - known as fecal microbiota transplantation (FMT). With this investment, we can pursue our randomized trial, with the goal of improving the lives of patients with advanced melanoma. We are optimistic that we will see promising results.” – Dr. Arielle Elkrief, principal investigator, Clinician-Scientist, Université de Montréal-affiliated hospital research centre (CRCHUM)

“Our early research has shown the safety of combining FMT with immunotherapy and that it may improve outcomes for patients with melanoma. Through this new trial, we hope to demonstrate that the combination is more effective than immunotherapy alone. A positive result would lead to a phase III trial with the potential to make FMT with immunotherapy the new standard of care.” - Dr. John Lenehan, Medical Oncologist at the Verspeeten Family Cancer Centre at London Health Sciences Centre and Associate Scientist at Lawson Health Research Institute, Co-chair of ME17 trial

The researchers and collaborators

The phase II clinical trial, known as the ME17 Fecal microbiota transplantation (FMT) in combination with immune checkpoint blockade in patients with advanced melanoma: A randomized phase II trial, involves several highly collaborative experts who will be working with the Canadian Cancer Trials Group (CCTG) who will administer the trial nationally. For the translational research associated with the trial, the project team includes: 

Co-Principal Investigators:
Dr. Janet Dancey, Medical Oncologist and Professor, Queen’s University, Director of the Canadian Cancer Trials Group  
Dr. Arielle Elkrief, Clinician-Scientist and Assistant Professor, Université de Montréal-affiliated hospital research centre (CRCHUM)
Dr. John Lenehan, Medical Oncologist at LHSC’s Verspeeten Family Cancer Centre, Associate Scientist, Lawson Health Research Institute 
Dr. Bertrand Routy, Clinician-Scientist and Associate Professor, Université de Montréal-affiliated hospital research centre (CRCHUM)
Dr. Saman Maleki, Scientist, Lawson Health Research Institute, London Health Sciences Centre's (LHSC) Verspeeten Family Cancer Centre and Ontario Institute of Cancer Research (OICR) 
Dr. Michael Silverman, Scientist, Lawson Health Research Institute, Medical Director of the Infectious Disease Care Program at St. Joseph’s Health Care London 
 
Collaborators:
Dr. Seema Parvathy, Lawson Health Research Institute
Dr. Marcus Butler, Leader of the CCTG Melanoma Disease Site Committee, Princess Margaret Cancer Center
Dr. Rahima Jamal, hemato-oncologist, researcher and medical director at the Unit for Innovative Therapies (Phase I-II Unit), Université de Montréal-affiliated hospital research centre (CRCHUM)
Dr. Ian Watson, Associate Professor and Co-chair CCTG Melanoma Disease Committee, McGill University
Dr. Bingshu Chen, Professor, Queen’s University
Dr. Meriem Messaoudene, Research Associate, Université de Montréal-affiliated hospital research centre (CRCHUM)

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About the Canadian Cancer Society
The Canadian Cancer Society works tirelessly to save and improve lives. We raise funds to fuel the brightest minds in cancer research. We provide a compassionate support system for all those affected by cancer, across Canada and for all types of cancer. Together with patients, supporters, donors and volunteers, we work to create a healthier future for everyone. Because to take on cancer, it takes all of us. It takes a society. Help us make a difference. Call 1-888-939-3333 or visit cancer.ca today.

About the Weston Family Foundation
At the Weston Family Foundation (formerly The W. Garfield Weston Foundation), more than 60 years of philanthropy have taught us that there’s a relationship between healthy landscapes and healthy people. That’s why we champion world-class health research and innovation with the same passion that we support initiatives to protect and restore biodiversity on our unique landscapes. We take a collaborative approach to philanthropy, working alongside forward-thinking partners to advance Canada and create lasting impacts. We aspire to do more than provide funding; we want to enable others to find transformational ways to improve the well-being of Canadians.

A team of authors from Lawson Health Research Institute and University Health Network (UHN) have released details on Canada’s first published case of suspected vaping-related lung injury. Published today in CMAJ, the case study may be the first to describe a new type of injury from vaping products.

The case differs from those described in the recent rise of vaping-related lung injuries called EVALI (e-cigarette or vaping product use associated lung injury), which are characterized by a specific type of damage called alveolar injury. This case instead represents a lung injury that appears similar to “popcorn lung,” a condition seen in microwave popcorn factory workers exposed to the chemical diacetyl. The condition causes bronchiolitis where the small airways in the lungs become inflamed and damaged.

The authors describe a case of life-threatening bronchiolitis in a 17-year-old Ontario male who initially sought care after a week of persistent cough. He was eventually hospitalized needing life support in the intensive care unit. After ruling out other causes in the previously healthy teen, the authors suspected flavoured e-liquids as the culprit. The patient had been vaping daily using a variety of flavoured cartridges and tetrahydrocannabinol (THC).

“This case of life-threatening bronchiolitis was challenging. The damage appeared similar to that seen in factory workers exposed to diacetyl,” explains lead author Dr. Karen Bosma, Associate Scientist at Lawson and Critical Care Specialist at London Health Sciences Centre (LHSC). “Given the patient’s vaping activity and the absence of other causes, we suspect his lungs became damaged from vaping compounds.”

The youth narrowly avoided the need for a double lung transplant. He spent a total of 47 days in hospital and suffered chronic damage to his airways. He is currently recovering from his lengthy intensive care unit stay and is abstaining from e-cigarettes, marijuana and tobacco.

"This case highlights significant harm that could come from vaping. This risk is particularly specific to teens and young people who are the largest users of these products," says Dr. Inderdeep Dhaliwal, Respirologist at LHSC. "Now with awareness, we hope this work stimulates further research on the mechanisms and causation of vaping-associated lung injury."

Earlier this fall, the Middlesex-London Health Unit reported on the youth’s condition as the first case of vaping-related lung injury in Canada as an early warning. This research case study provides detailed medical information on the extent and type of injury, as well as treatment. Emerging reports indicate that e-cigarettes are causing a variety of lung illnesses and injuries. According to a 2017 report, e-cigarettes are the most commonly used nicotine products by Canadian youth with an estimated 272,000 reporting use within the last 30 days.

“E-liquids expose users to several potentially harmful chemicals. While we can’t be sure of the exact mechanism in this case, it was reported to Health Canada for further investigation,” says Dr. Constance Mackenzie, Respirologist and Toxicologist at LHSC and St. Joseph’s Health Care London. “It highlights the need for further research into the safety and toxicity of e-liquid compounds, and awareness of the various types of lung injury that can result from vaping.”

 

"We want the medical community to be aware that vaping-related lung injury may present in many different ways, and to report any cases to Health Canada for further investigation," says Dr. Simon Landman, Medical Fellow at LHSC. "We are urging patients and their families to take vaping-related lung injury seriously, and recognize that vaping may cause both short- and long-term injury to the lungs."