Program: CANTRAIN

Fragility fractures of the pelvis are a very common injury in the elderly and are increasing in incidence with an aging population. These injuries are associated with high healthcare costs as well as poor patient outcomes, including decline in function and decreased independence. Historically, older adults with fragility fractures of the pelvis received nonoperative treatment with supportive care because operative management was deemed too invasive for this patient population. However, the development of percutaneous and less invasive surgical techniques has led to an increased frequency of operative stabilization of pelvis fractures in older adults. It is unclear if the increasing use of surgical fixation is improving outcomes for patients with pelvic fragility fractures. A definitive trial is urgently needed to help guide treatment decision making in this injury population. 

Dr Sepehri is an orthopaedic trauma surgeon at Vancouver General Hospital who has experience and expertise in conducting research that focuses on challenging acute fractures of the extremities and pelvic ring. Dr Sepehri received funding from the Orthopaedic Trauma Association (OTA) to lead a feasibility study to support and inform the design of a definitive Randomized Controlled Trial evaluating operative treatment of fragility fractures of the pelvic ring. This study is an international collaboration with sites in Canada, USA and Spain. Supported by the CANadian Consortium of Clinical Trial TRAINing Platform (CANTRAIN)-Clinical Trials Training Programs, funded by Michael Smith Health Research BC, Dr Sepehri will receive mentorship from Dr Sheila Sprague, Research Director and Associate Professor within the Department of Surgery at McMaster University. Dr Sprague has expertise in the design and conduct of large RCTs with an established track record for mentoring early career surgeon scientists. 

This project, supported by the 2024 CANTRAIN competition, focuses on developing and evaluating innovative clinical trial designs to enhance efficiency and reliability. Led by BC Principal Investigator Denghuang (Jeff) Zhan, a third-year doctoral student at UBC, this BC-based research integrates modern statistical approaches to address challenges in clinical trials.

The study builds on insights from the THREE-D trial, a groundbreaking study that evaluated treatments for patients with treatment-resistant depression (TRD). Traditional clinical trials, like the THREE-D trial, often require large sample sizes and fixed designs, which can be inefficient and inflexible. This research introduces a Bayesian adaptive design framework, which allows trials to adjust in real time based on accumulating data, improving efficiency and reducing costs.

By employing advanced simulation methods, including plasmode simulation (a technique using real-world data with controlled modifications), this project compares the performance of Bayesian adaptive designs with traditional fixed designs. Key benefits of Bayesian adaptive designs include the ability to stop trials early for efficacy or futility, more precise treatment effect estimation, and reduced sample size requirements without compromising statistical power.

The anticipated outcomes of this work include:

• Improved trial designs that are more responsive to real-world data.
• Practical guidelines for implementing Bayesian adaptive designs in clinical research.
• Enhanced methodologies that could accelerate treatment evaluation in areas like psychiatry and beyond.

This research will not only advance statistical methodologies but also contribute to the broader goals of Learning Health Systems (LHS), enabling healthcare systems to learn and adapt quickly to new evidence. By making trials faster, more flexible, and cost-effective, this work has the potential to improve healthcare delivery and patient outcomes.

Colorectal cancer is the second most deadly cancer in Canada. Treatment typically involves surgery and chemotherapy, which can be effective but also cause significant side effects and not always prevent the cancer from returning. The DYNAMIC-III/CO.29 study is a major international clinical trial led by BC-based researcher and medical oncologist, Dr. Jonathan Loree based at the University of British Columbia and associated with the BC Cancer Agency. The trial involves 1000 patients who have had surgery for stage III colorectal cancer and is investigating a new approach that identifies fragments of tumor DNA in the blood, called circulating tumor DNA (ctDNA), to tailor chemotherapy more closely to each patient’s needs. By checking for ctDNA shortly after surgery, doctors can adjust the intensity of chemotherapy—either increasing it if ctDNA is detected, suggesting remaining cancer, or reducing it if no ctDNA is found, to spare unnecessary side effects.

Assistance from the CANTRAIN-CTTP & Michael Smith Health Research BC Masters’ Studentship 2024 Award Program supports this major clinical trial through Masters’ Student, Michael Diaz-Stewart’s whose work on evaluating colorectal cancer subtypes through artificial intelligence-based screening ties into the wider project. This award contributes to BC-based frontier research aiming to improve our ability to precisely treat colorectal cancers through revised practices and artificial intelligence-informed screening.

End of Award Update – July 2025

Results

With the support of the CANTRAIN and Michael Smith Health Research BC fellowship, I participated in a structured series of training activities designed to enhance knowledge and skills in clinical trial research. These included online modules and group-based sessions on trial methodology, regulatory requirements, and clinical trial good practice. I was also matched with an experienced mentor, with whom I virtually met monthly to discuss both the scientific and practical aspects of launching an investigator-initiated clinical trial.

Impact

The support of this fellowship contributed to the development and initiation of the NeoBLAST trial, now actively recruiting in British Columbia. The trial explores bladder preservation strategies for patients with muscle-invasive bladder cancer who achieve a complete response after neoadjuvant treatment, addressing a critical gap in care. In addition to contributing to lauch of this exciting clinical trial, this project will also helped build a foundation for translational research and patient-centered innovation in urologic oncology in BC.

Potential Influence

NeoBLAST has the potential to change clinical practice by identifying patients who may avoid radical cystectomy without compromising oncologic outcomes. If successful, the trial could inform national and international guidelines on bladder cancer management. Additionally, correlative studies will also be done to investigate other potential biomarker of response and surveillance of recurrence of disease.

Future Research

The current Phase II feasibility study will be enrolling patient accros the province, and we will plan to expend to into a multi-centre Phase III trial pending proof of feasibility (Phase II) and additional funding. We are also pursuing translational studies on biospecimens collected through the trial to explore use of urine derive tumor DNA (utDNA), radiomics and additional immunologic markers with collaborators from the Vancouver Prostate Centre.

Best research practices and honest reporting are cornerstones of science. Society assumes that research is performed carefully and reported openly. But there are unseen threats to science—85% of the investment in biomedical research is avoidably wasted due to poor conduct and reporting of research results. When we rely on science to inform decisions about patient care and health policy, society must strive for reliability in science. 

Only 3 out of every 100 clinical trials conducted in Canada between 2009 and 2019 provided enough information for researchers, clinicians, patients and policymakers to decide whether the research is meaningful and worth implementing in practice. 

I will lead a project to develop and evaluate an online training programme that aims to teach researchers how to maintain an accurate public record of their research—from its beginning all the way through to sharing the results with the scientific community and the public. The training program will roll out across at least 12 universities (out of 16) in British Columbia and culminate in testing how well researchers and institutions in British Columbia register and report the results of their research. 

Sudden cardiac arrest (SCA) is a major health issue where the heart unexpectedly stops beating, and blood no longer circulates through the body. In Canada, there are about 60,000 cases of SCA each year. Quick action, such as starting cardiopulmonary resuscitation (CPR), is crucial. The longer it takes to start CPR, the less likely a person is to survive. Unfortunately, most SCAs happen in places where no one is around to help. Therefore, one of the biggest challenges in improving survival rates is the delay in recognizing that a cardiac arrest has occurred. Consumer wearable technologies have great potential to continuously monitor cardiac function and automatically recognize signs of disruption or loss of blood circulation at any time. If a problem is detected, these devices could automatically call emergency services for help. Our previous studies have shown that wearable sensors combined with artificial intelligence (AI) can recognize some signs and symptoms associated with a cardiac arrest, such as absence of a pulse. The overarching goal of the proposed project is to validate the performance of such a system for real-world SCA detection. 

Infants born extremely prematurely, especially before 26 weeks’ gestational age (GA), are classified as micropreemies and are considered the most vulnerable population. These babies often face serious short and long-term health challenges. One common problem is intraventricular hemorrhage (IVH), a type of brain bleed that remains the leading cause of death in this vulnerable population. Severe IVH (sIVH) can lead to significant lasting effects such as cerebral palsy, reduced IQ, and overall neurodevelopmental disabilities. Clinical trials have shown that preventative indomethacin, a nonsteroidal anti-inflammatory drug, can prevent sIVH and death. In Canada, babies born before 26 weeks’ GA from 2018-2022 who received indomethacin had a 5% lower death rate and were 4% more likely to survive without sIVH in comparison to those who did not receive the drug. Although past studies have shown that prophylactic indomethacin can reduce both sIVH and death, its use in clinical practice remains inconsistent due to concerns about potential negative effects. The proposed study, PRophylactic Indomethacin in MicropreemiEs (PRIME), specifically examines the impact of prophylactic indomethacin on short- and long-term neurodevelopmental outcomes in the micropreemie cohort. The pan-Canadian retrospective observational study will link data from the Canadian Neonatal Network and Canadian Neonatal Follow Up Network to investigate the relationship between preventative indomethacin and death and disability in extremely premature infants. Additionally, neurodevelopmental outcomes will be explored at 18-24 months. Una Spasovski, a master’s student in the Women+ and Children’s Health program at the University of British Columbia, will lead this study in British Columbia. Under the supervision of Dr. Souvik Mitra, her research specifically focuses on improving outcomes for extremely premature infants at the BC Children’s Hospital Research Institute.

One of the most devastating consequences of cervical spinal cord injury (cSCI) is the loss of hand movements, which severely impacts independence and quality of life. Nerve transfer surgery (NT) is emerging as a promising method to restore functions like hand opening and closing. While previous research shows NT is safe and potentially effective, robust scientific evidence of the effectiveness of NT is lacking. To address this gap, a national collaborative effort led by BC-based physiatrist and clinical assistant professor Dr. Michael Berger is conducting the first multi-centre prospective study on NT for individuals with cSCI (https://clinicaltrials.gov/study/NCT05638191). The primary aims of this study are to evaluate NT’s overall effectiveness in individuals with cSCI, identify patient subgroups most likely to benefit from NT based on factors like age and injury level, and explore patients’ lived experiences post-surgery. This study, supported by the CANTRAIN-CTTP & Michael Smith Health Research BC Post-Doctoral Fellowship 2024 Award Program, is being conducted across four Canadian interdisciplinary clinical programs (Vancouver, BC; Toronto, ON; Kingston, ON; Halifax, NS). Over four years, participants will undergo comprehensive assessments at baseline and regular intervals for 24 months post-surgery, enabling researchers to track changes in functional, motor, and patient-reported outcomes. By rigorously evaluating the efficacy, safety, and broader impacts of this innovative surgical technique, our team aims to provide individuals with cSCI the knowledge and confidence to make informed decisions about their treatment options.