Implementation-effectiveness Trial of Mainstreaming of Clinical Genomic Sequencing for Rare Disease in Ontario, Canada

Mainstreaming of Clinical Genomic Sequencing for Rare Disease in Ontario, Canada: Protocol for a Province-wide Hybrid Type 2 Implementation-effectiveness Trial

Genomic sequencing (GS) is increasingly recommended as a diagnostic test for patients with suspected genetic disorders, but access often remains limited to those referred to medical geneticists. Enabling non-geneticist clinicians to access GS can expedite diagnoses for affected families and reduce burdens on the geneticist-led model of care. Targeted implementation strategies are needed to empower non-geneticist clinicians to access GS, however data to inform these strategies are lacking. To this end, the investigators have set out to carry out a prospective, hybrid implementation-effectiveness trial of mainstreamed clinical GWS in Ontario, Canada. The study team will evaluate the laboratory, clinical, patient and implementation outcomes of the mainstreamed model of care.

Study Overview

• Status: Not yet recruiting
• Conditions: Genetic Disease; Neurodevelomental Disorders; Evaluation of Mainstreamed Models of Genetic Service Delivery
• Intervention / Treatment: Genetic: Genome-wide Sequencing Ordering

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Erin Hsue, HBSc, MHSc; Phone Number: 414638 416-813-7654; Email: grip.study@sickkids.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients who have received genome-wide sequencing in Ontario

Description

For intervention outcomes,

- All patients who have received genome-wide sequencing in Ontario are eligible

For implementation outcomes,

• All non-geneticist clinicians practicing in Ontario who have ordered genome-wide sequencing for their patients are eligible
• Caregivers of patients who have had genome-wide sequencing through a non-geneticist clinician in Ontario are eligible, caregivers must be over 18 years of age

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Standard Arm; Patients receiving GWS through geneticists in Ontario	Genetic: Genome-wide Sequencing Ordering; Delivery of genome-wide sequencing (encompasses all activities involved in pre-test and post-test including clinical assessment, ordering, consent, education, return of results, post-test management)
Intervention Arm 1; Patients receiving GWS through non-geneticists in Ontario	Genetic: Genome-wide Sequencing Ordering; Delivery of genome-wide sequencing (encompasses all activities involved in pre-test and post-test including clinical assessment, ordering, consent, education, return of results, post-test management)
Intervention Arm 2; Patients receiving GWS through non-geneticist clinicians at designated sites in Ontario with additional implementation strategies	Genetic: Genome-wide Sequencing Ordering; Delivery of genome-wide sequencing (encompasses all activities involved in pre-test and post-test including clinical assessment, ordering, consent, education, return of results, post-test management)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic utility	The proportion of causative, pathogenic or likely pathogenic genotypes in known disease genes. This will be reported as the proportion of cases for whom diagnostic and partially diagnostic, and non-optional medically actionable secondary findings are identified at the time of primary analysis and re-analysis. Proportion of cases for whom optional medically actionable secondary findings will also be reported, relative to the number of cases who opted to receive them.	From January 2025 to August 2027

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability	Satisfaction with Genome-wide Sequencing Ontario (GSO) intervention and implementation among ordering providers (geneticists and non-geneticists), GSO leadership, laboratory, patients and families. This outcome will be measured using a team-developed questionnaire with a 5-point Likert scale with 1 indicating strongly disagree and 5 indicating strongly agree.	12 months from enrolment
Feasibility	Fit and suitability for regular use by ordering providers. This outcome will be measured using a team-developed questionnaire with a 5-point Likert scale with 1 indicating strongly disagree and 5 indicating strongly agree.	12 months from enrolment
Sustainability	Sustainability is defined as the extent to which the Genome-wide Sequencing Ontario (GSO) service can be maintained within a clinical practice. This outcome will be measured using a team-developed questionnaire with a 5-point Likert scale with 1 indicating strongly disagree and 5 indicating strongly agree.	12 months from enrolment
Timeliness	Timeliness is defined as the time needed to reach a molecular diagnosis. For routine cases, this will be reported as the proportion of cases for whom laboratory turnaround time is less than 12 weeks. From a laboratory perspective timeliness will be measured as the number of weeks elapsed from sample accessioning to laboratory reporting, reported as the proportion of cases for whom laboratory turnaround time is less than 12 weeks. The study team will also assess timeliness from the patient perspective using a patient experience questionnaire that addresses this dimension of care.	From January 1, 2025 to August 31, 2027
Cost-effectiveness	The cost per case of community-based genetic service delivery will be measured. This will include sessions with physicians and genetic counselors and laboratory sequencing costs. Laboratory costs will be determined by updating existing microcost estimates of the laboratory workflow components for sequencing approaches. If a comparative design is possible, a cost analysis will compare service delivery cost for non-geneticist clinicians compare to geneticist clinicians.	From January 1, 2025 to August 31, 2027
Adoption	Adoption is defined as the total number of non-geneticist clinicians ordering Genome-wide Sequencing Ontario (GSO) for their patients, and total number of submitted cases per clinician, assessed through the GSO REDCap database.	From January 1, 2025 to August 31, 2027
Fidelity	Fidelity is defined as adherence to the Genome-wide Sequencing Ontario (GSO) workflow (including form completion, use of appeal process), measured by time (in days) between when the GSO order is accessioned in the lab and when the order is processed and sent for sequencing.	From January 1, 2025 to August 31, 2027
Penetration	Penetration is defined as the degree of integration within a service delivery system (i.e., proportion of eligible clinicians who offer genome-wide sequencing (GWS)). This outcome will be measured by iteratively assessing the rate of requests for GWS based on total eligible clinicians. This outcome will be reported based on practice characteristics of the requesting clinician (specialty, geography, years in practice, etc.).	From January 1, 2025 to August 31, 2027
Acceptability (to patients/families)	Acceptability (to patients/families) is defined as the experiences of patients or their family members during their participation in the mainstreamed model of care. This outcome will be measured using a team-developed questionnaire with a 5-point Likert scale with 1 indicating strongly disagree and 5 indicating strongly agree.	From enrolment to August 31, 2027

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Robin Z Hayeems, ScM, PhD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: August 18, 2026
• First Submitted That Met QC Criteria: August 28, 2026
• First Posted (Actual): September 2, 2026

Study Record Updates

• Last Update Posted (Actual): September 2, 2026
• Last Update Submitted That Met QC Criteria: August 28, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: rare disease; implementation; genomic sequencing; neurodevelopmental disease; mainstreaming; genome-wide sequencing
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Rare Diseases; Genetic Diseases, Inborn
• Other Study ID Numbers: CTO #5637; KMI 181800 (Other Grant/Funding Number: Canadian Institutes of Health Research (CIHR))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No