Medical trainees looking to gain experience in independent research have few options for funding support. But education and training, not just in clinical practice but also in how to conduct research, are critical to ensure that trainees can confidently pursue careers as clinician-scientists and pursue research that will change clinical practice.

PSI Foundation’s Resident Research Grants, which award up to $30,000 for up to two years, provide key funding to support these young investigators. The grants are part of PSI’s vision to support new investigators and ensure that physicians are well-equipped to lead innovative research and provide excellent health care.

“There are not that many opportunities as a junior investigator to have your own funding before your first academic position,” says Dr. Jodi Warman-Chardon, Director, Neuromuscular Centre and clinician-scientist at The Ottawa Hospital (Research Institute) and Children’s Hospital of Eastern Ontario (Research Institute) (CHEO), who received a PSI Resident Research Grant in 2013. “The PSI funding is critical for creating the clinician-scientist leaders of tomorrow.”

For many trainees, a PSI Resident Research Grant provides invaluable experience in their training toward becoming an independent investigator. Residents lead the research and are the main contact for the grant, providing them with invaluable learning opportunities in every aspect of leading a grant, including administration.

Dr. Warman Chardon was completing a neurogenetics/neuromuscular fellowship at the University of Ottawa and CHEO when she was awarded a PSI Resident Research Grant. With supervisor Dr. Kym Boycott, Dr. Warman-Chardon studied next generation genetic sequencing to diagnose limb girdle muscular dystrophy (LGMD), a group of inherited muscle disorders. They were able to identify disease-causing variants in genes known to be important to the condition, and they discovered a new gene responsible for early-onset disease.

The work resulted in several publications (including Clinical Genetics and Current Neurology and Neuroscience Reports) and several national and international presentations, including a poster at PSI’s Annual General Meeting in 2016, for which she won the best poster award. “The generosity and ongoing support of PSI has launched many investigators’ careers and is a real capstone for a trainee,” she says. “These grants change your career trajectory.”

Based in part on the data from the Resident Research Grant, she received a PSI New Investigator Grant in 2019, with Dr. Boycott as co-principal investigator. This research project aims to integrate MRI, genome sequencing and RNA sequencing to improve diagnosis for genetic myopathies, thus improving care.

“These clinician-led projects are not always attractive projects for other granting agencies, but they do change care,” says Dr. Warman Chardon. “These grants help advance patient care that we would not otherwise be able to do, and on behalf of my patients with these rare diseases, I’m incredibly grateful for PSI’s support.”

Areas of non-support excluded from Resident Research Grants 

Dr. Bobby Yanagawa, a heart surgeon at St. Michael’s Hospital and Program Director in the Division of Cardiac Surgery at the University of Toronto, had already completed a PhD and a post-doctoral fellowship when he started his surgical residency in 2008. He received two PSI Resident Research Grants, in 2009 and 2012, to study two different proteins and their roles in cardiac injury and cardiovascular disease.

Dr. Yanagawa says that as a surgical trainee, he had a keen interest in research but limited time to conduct it, which made it difficult to secure funding from large agencies. PSI’s support was critical to helping him build a research program while completing his training.

“This funding is like a catapult,” he says. “It gives people who have a project of smaller scope the opportunity to publish some papers and generate some momentum.”

Importantly, while PSI does not typically fund research in certain areas, such as cancer and heart disease, these areas of non-support do not apply to Resident Research Grants. Dr. Yanagawa says this exception is critical for clinician-scientists at the beginning of their careers who may not yet have the track record to successfully apply for large grants from national agencies.

“There needs to be funding for the researchers who can’t compete at the national agencies and for pilot projects and innovative ideas that it’s hard to get the big dollars for,” he says. “Without this funding, the trainees in cancer and cardiovascular disease would suffer. It’s really important and very much appreciated.”

Dr. Yanagawa now supervises trainees leading their own research projects, including studies of rheumatic heart disease, training using surgical simulations, and gender equity in surgical training. He says that supervising residents is a way to show appreciation for the support he received during his training and share his knowledge with the next generation of clinician-scientists.

“It’s nice to be part of that continuum, and I enjoy being part of that process,” he says. “To have the opportunity to work on the project with a resident, get them to drive it, successfully get grant funding and eventually see the fruits of that research is very satisfying.”

“PSI has a long history of funding important clinical and practical questions that have a high potential to improve the practice of medicine.” – Dr. Kathy Boutis

As a pediatric emergency physician at Toronto’s Hospital for Sick Children (SickKids), Dr. Kathy Boutis has treated many children with minor musculoskeletal injuries. Her research program, with significant support from PSI Foundation, has helped to shape how physicians at SickKids and around the world treat and manage these common injuries.

“I am first a doctor and I love being a doctor,” she says. “I wanted to do research in an area where emergency physicians could lead the path to change using high quality evidence.” Hundreds of thousands of children present to Ontario’s emergency departments with minor musculoskeletal injuries every year, and Dr. Boutis recognized the impact she could have by studying them.

She began working with Dr. Suzanne Schuh on a project to predict the need for radiography in children with ankle injuries, the results of which were published in The Lancet in 2001. In 2002, she received her first PSI Foundation grant as a principal investigator, comparing a removable brace to a cast for low-risk ankle fractures. The results demonstrated that the brace allowed children to recover and return to physical activity quicker than casting, and was more cost-effective and preferred by patients. These two studies formed the building blocks of what was to become a successful research program over the next two decades.

Research aims to help physicians “choose wisely”

Dr. Boutis has since been principal investigator on three more PSI grants, all of which have focused on de-escalating interventions for minor musculoskeletal injuries in children. Casting and other interventions can occasionally cause complications, but the benefits of de-escalating the interventions go beyond reducing complications and include the potential to reduce health care costs and improve the quality of life for injured children and their families.

“Our overall goal is to optimize the diagnosis and management of pediatric musculoskeletal injuries. It appeals to the current interest and demand in choosing wisely,” she says. “We need to look at managing these common problems to be more resource-efficient and convenient for patients.”

She and her team received PSI funding to evaluate the Low Risk Ankle Rule, a clinical guideline for when children presenting with ankle injuries benefit from ankle x-rays. Implementing the rule safely reduced the rate of x-rays given to children by about 50%. This rule is now being adopted by emergency departments all over the world. She then noticed that one type of common minor ankle injury, presumed to be a fracture, was treated for weeks with a cast, which seemed unnecessary. PSI funded a project that studied this injury using magnetic resonance imaging (MRI) and found that most kids with this injury, in fact, did not have a fracture – rather they had ankle sprains that could be managed with rest, ice, and return to activities when the child was ready. Her most recent grant awarded by PSI in 2019 is extending these principles to a minor leg fracture in toddlers, with the hopes of creating an equally safe but more convenient treatment for these injuries. “Parenting a toddler is challenging enough without the addition of restricting their activity for weeks,” she says. “If we can make managing these injuries easier, it’s a win for parents and the health care system.”

Growing out of her PSI-funded work, it became obvious that emergency physicians found pediatric image interpretation challenging, which led to medical errors. As a result, Dr. Boutis also implements cutting-edge medical education theory into the teaching of medical image interpretation, such as that required for x-rays and ultrasounds. This research eventually led to the development of ImageSim, an award winning and nationally acclaimed innovative web-based image interpretation learning system.

Study results have changed clinical guidelines around management of minor injuries

Studying minor injuries in pediatric emergency medicine is a niche area of research that has limited funding opportunities, and Dr. Boutis says that PSI Foundation funding has been critical. “PSI has been pivotal to my work,” she says. “They have always been very fair and transparent. I feel very positively about the organization and their mission.”

PSI funding has allowed Dr. Boutis to complete high quality multicentre trials that have made a significant impact in the field. She has published in numerous high impact journals, and her work has caught the attention of leading textbooks in the field. These efforts led to the development of clinical guidelines around management of minor musculoskeletal injuries internationally – which helped her realize her goal of making an impact on emergency medicine practice. “If my work never got implemented at the bedside, it would feel like all the evidence I derived failed,” she says. “One of the best compliments I receive is from my colleagues is that it makes them better doctors. You could not get a better compliment than that.”

“PSI funds a diversity of different types of clinical research – the whole gamut of medical and surgical specialities. It’s amazing what PSI has been able to accomplish in so many different areas.” – Dr. Ian Gilron 

Dr. Ian Gilron, an anesthesiologist at Kingston Health Sciences Centre and professor at Queen’s University, credits PSI Foundation funding for advancing his team’s research on combination therapy for acute and chronic pain. “When I was first getting involved in this field more than 25 years ago, pain management was such a big area of clinical need and there were lot of unanswered research questions,” says Dr. Gilron. “That continues to be the case, although we have made much progress.”

Pain helps to protect the body and alerts it to harm, and because of this important role many different neural pathways transmit pain. As a result of the many mechanisms involved, treating pain is challenging. A single pain drug by itself is unlikely to be highly effective for many patients, but rather combinations of treatments that target different pathways are often used.

Dr. Gilron has focused his team’s research program on evaluating drug combinations to treat both acute and chronic pain. “The first three project grants we got from PSI absolutely advanced the field in understanding multimodal drug therapy for acute pain, and a lot of those principles are also being applied in chronic pain,” he says. “The work funded by PSI has really helped advance that field.”

In particular, Dr. Gilron’s PSI-funded research has focused on understanding the treatment and impact of movement-evoked pain after surgery. His research suggested that movement-evoked pain may have different mechanisms than pain at rest, and it often does not respond to opioids in the same way as pain at rest.

His first three PSI Foundation grants funded single-centre clinical trials of drug combinations to treat movement-evoked pain after abdominal surgery: a study comparing a two-drug combination of rofecoxib and gabapentin to either drug alone, a study comparing meloxicam and gabapentin together to either drug alone, and a study comparing a triple combination of acetaminophen, meloxicam and gabapentin to any two of the drugs together. In each study, pain levels and other measures of physical function were improved with combination treatment at various timepoints after surgery.

New research is evaluating antioxidant’s effectiveness for pain 

At the same time as Dr. Gilron was leading this work in acute pain, he was also conducting proof-of-concept clinical trials of drug combinations for chronic pain.

These clinical trials were published in high-impact journals, including The Lancet and The New England Journal of Medicine, and Pain, and they all showed that the combination therapies being evaluated were more effective than any one of the drugs alone. “The improvement we observed with the combination was statistically significant, but it was a moderate improvement. We were hoping for more,” says Dr. Gilron. He adds that the side effects of each drug being tested, particularly the sedative effects, limited the dosages and, therefore, the added effectiveness of the combination therapies.

His most recent research is evaluating a possible treatment that has no sedative side effects, making it an ideal “partner” to combine with other pain drugs that do have this sedative effect. Recent studies have suggested that the antioxidant alpha-lipoic acid relieves pain in nerve conditions such as diabetic neuropathy without a sedative effect, and it could potentially be used in combination therapy for other chronic pain conditions such as fibromyalgia.

Building on this previous work and the need to identify new non-sedating chronic pain treatments, in 2015, Dr. Gilron received PSI funding for a proof-of-concept clinical trial studying the effects of alpha-lipoic acid on pain relief in fibromyalgia. The results, recently published in Pain, did not suggest that alpha-lipoic acid is an effective treatment for fibromyalgia in most patients, although there was a trend for pain reduction in male patients with fibromyalgia. As such, this trial represented an important step in research to identify new treatments for chronic pain.

“PSI is willing to take chances on new ideas. It is very focused on funding high quality research and skilled investigators, so they don’t take a risk in that perspective, but certainly it is willing to support new ideas and innovation,” says Dr. Gilron. “For PSI to keep our combination research program advancing for so many years then give us the opportunity to bring our research in a whole new direction is something quite unique.”

“PSI Foundation really understands translational research and the idea of the clinician scientist. The Foundation has a unique position in supporting clinically relevant research, and this has been an important contribution to science in Ontario, and therefore nationally and internationally.” – Dr. Michael Fehlings, Toronto Western Hospital and University of Toronto

Dr. Michael Fehlings, a neurosurgeon at Toronto Western Hospital and professor in the University of Toronto’s Department of Surgery, was first exposed to the idea of translational research and the role of clinician scientists as a medical student. “I was impressed that by asking key questions related to medical practice, one could generate research that could change the way you treat a patient,” he says.

During his research career, he has focused on spinal cord injuries, specifically secondary spinal cord injuries – the biochemical processes such as inflammation and generation of reactive oxygen species that cause cell death following an initial spinal cord injury. Because these secondary injuries can exacerbate the initial injury, understanding these mechanisms is critical to develop new treatments. Dr. Fehlings says that PSI Foundation’s support of translational research has been critical to his research program.

PSI Foundation has funded his research for more than 25 years, from his early basic research on the mechanisms of secondary injury to more recent translational studies of biomarkers for degenerative spinal conditions. “PSI Foundation had the confidence to allow me to come forward with various ideas over the years,” he says. “A number of these strategies funded by PSI Foundation have now become translated into therapeutics or clinical trials.”
One of the first significant discoveries in his career, partially funded by PSI Foundation, demonstrated that when sodium enters nerve cells after an injury, it amplifies nerve cell damage. Based on this discovery, the sodium channel blocker riluzole, which is approved for treatment of amyotrophic lateral sclerosis (ALS), is now in phase 3 clinical trials to improve outcomes for traumatic spinal cord injuries.

Over the years, he and his team have studied whether intravenous IgG, approved for treatment of various inflammatory conditions, is effective in reducing secondary spinal injury, and in enhancing recovery after surgery for degenerative cervical myelopathy (DCM), a degenerative form of arthritis. This work is now in late preclinical stages. They also developed a novel bioengineered system to deliver drugs to treat spinal cord injuries, which served as a critical proof of principle for current delivery systems being tested in clinical trials.

Dr. Fehlings says that PSI Foundation support was essential to these discoveries. “In each case, we were able to leverage PSI funding several fold, bringing in additional grants and industry support to move it forward to clinical trials,” he adds.

Support from the PSI Foundation has been instrumental in a number of discoveries throughout his career that have garnered him international recognition. In 2009, he was awarded the Olivecrona Award, the top international award for neurosurgeons and neuroscientists awarded by the Nobel Institute at the Karolinska Institute in Stockholm, for his important contributions in central nervous system injury repair and regeneration. In 2014, Dr. Fehlings was elected to the Fellowship of the Royal Society of Canada and to the Canadian Academy of Health Sciences, and last year the Right Honourable Jacinda Ardern, Prime Minister of New Zealand, presented him with the Ryman Prize for his work enhancing the quality of life for older people.

His most recent PSI Foundation grant, awarded in 2017, is more directly translational. He and his team are studying whether genetic biomarkers in blood samples can identify individuals who are more susceptible to DCM. Identifying these patients would allow for earlier, possibly even preventive, treatment. Early results have been very promising, and the work will be published soon.

Dr. Fehlings’ research, directly or partially funded by PSI Foundation, has led to results that have influenced clinical practice guidelines and enhanced outcomes for patients. “Translational work is always evolving,” he says. “Being a clinician-scientist has allowed me to ask critical questions and make a positive impact to help with innovative treatments.”