System Outcomes Projects

Motivated to establish a high-quality, timely, and cost-effective genome sequencing service for Ontarians with rare diseases, Genome-wide Sequencing Ontario (GSO) developed an innovative, harmonized, multi-institutional model for implementing and accessing the performance of exome and genome sequencing. 

By developing a centralized approach for sequencing and bioinformatic analysis, coupled with a distributed, institution-based mechanism for variant interpretation and reporting, GSO produces process and outcome data that will inform provincial and cross-provincial policy related to long-term organization, delivery, and reimbursement of genome diagnostics. 

Beyond the diagnosis of rare diseases, exome and genome sequencing can identify secondary findings (SF). SF are genetic variants that are unrelated to the indication for testing but are associated with medically actionable health risks. In partnership with GSO and key stakeholders, the SFIS aims to identify and describe the impacts of SF on patients, families, providers, and the health care system. This study will also look at the laboratory and health system costs associated with identifying, reporting, and following up on SF by leveraging GSO’s sequencing and result-reporting infrastructure. Findings from this study will help inform clinical practice and policy decisions around the use of genome diagnostics for rare diseases. 

Currently, access to GSO is limited to patients assessed by a medical geneticist and/or a genetic counsellor. However, there are long wait times to access genetics providers and many families who are eligible for genome-wide sequencing (GWS) are cared for by other types of providers (developmental pediatricians, neurologists, etc.). 

“Mainstreaming” has emerged to improve access to genetic testing by enabling non-genetics providers to order genetic testing themselves, saving families the step of waiting for a referral to genetics.  

Using a mixed methods hybrid implementation-effectiveness design and in partnership with CHILD-BRIGHT Network, the GRIP Study will: 

• Explore barriers and facilitators to the uptake of GWS among non-geneticist providers to inform the development of a mainstreaming model of care. 
• Leverage patient, provider, and laboratory partnerships to co-design, test, and implement a mainstreaming model of care with and for patients with brain-based developmental disabilities and other genetic conditions. 
• Determine the clinical, patient and implementation outcomes of the mainstreamed model of care to inform related activities across Canada.   

 In a related project, we are using a comparative case study design to identify factors associated with the effective implementation of genome sequencing in four Canadian provinces (Ontario, Alberta, British Columbia, Manitoba) and how these factors shape the clinical practices for rare disease diagnostics. 

C4R-SOLVE is a pan-Canadian collaboration among clinicians, scientists, and researchers focused on improving the care of individuals with rare diseases. 

In phase 1, we collected evidence on the impact of genome wide sequencing on medical management and associated health system costs from patient cohorts in Ontario and Alberta. Data were collected through medical record review and linkage to administrative datasets at the Institutes for Clinical and Evaluative Sciences and Alberta Health Services.  

With these data, we aim to:  

• Define and describe diagnostic testing pathways for patients with rare diseases before exome and genome sequencing  
• Determine the diagnostic utility of exome and genome sequencing 
• Determine the clinical utility of exome and genome sequencing 
• Determine the cost and utilization of healthcare services prior to and following exome and genome sequencing 
• Estimate the cost-effectiveness of exome and genome sequencing compared to conventional diagnostic testing pathways. 

This information will provide insight into the diagnostic utility, clinical utility, and cost consequences of clinical sequencing. Ultimately, we hope this research will inform policy decisions related to the appropriate use of novel genomic technologies for rare diseases. 

The clinical delivery of genome sequencing is complex and costly, resulting in unequal access, long wait times, workforce burdens, and high variability in practice. Prompted by the digital switch during the COVID-19 pandemic, we worked with Dr. Yvonne Bombard’s team at St. Michael’s Hospital to develop and evaluate a digital navigation platform called The Genetics Navigator.

The Genetics Navigator is an e-health platform that helps guide patients through genetic services. The Genetics Navigator aims to improve access, reduce wait times, and remove administrative burdens. It collects medical/family history, provides genetic counselling, and returns results to patients, allowing healthcare providers to focus on what matters most – the patient.

A randomized controlled trial of The Genetics Navigator is set to launch soon. This trial period aims to evaluate its effectiveness, cost-effectiveness, and user experience compared to conventional care practices with patients undergoing genetic testing.

The risk of developing Type 1 Diabetes (T1D) can be identified years before clinical symptoms develop. Being able to identify and follow up with those at risk may enable access to treatment and delay disease onset, reducing the risk of negative effects, like diabetic ketoacidosis. Early identification may also allow access to therapeutic clinical trials. However, there are technical, ethical, and health system challenges to developing a general population screening program – this is where the CANSCREEN T1D study comes in. 

Through our pan Canadian research consortium, we will investigate the feasibility and acceptability of T1D screening in the general population to inform the design of a pilot screening program. 

Planned projects include: 

• A citizens’ engagement and stakeholder dialogue to assess the acceptability of a range of screening program options. 
• Feasibility studies related to the use of polygenic risk scores and auto-antibody screening assays as screening tools. 
• Development and testing of patient education materials, decision aids, and genetic counselling strategies for polygenic risk scores. 
• Pilot screening program that includes monitoring and follow-up protocols.