TY - JOUR T1 - Comparing genome sequencing technologies to improve rare disease diagnostics: a protocol for the evaluation of a pilot project, Genome-wide Sequencing Ontario JF - CMAJ Open JO - CMAJ SP - E460 LP - E465 DO - 10.9778/cmajo.20210272 VL - 10 IS - 2 AU - Robin Z. Hayeems AU - Christian R. Marshall AU - Meredith K. Gillespie AU - Anna Szuto AU - Caitlin Chisholm AU - Dimitri J. Stavropoulos AU - Viji Venkataramanan AU - Kate Tsiplova AU - Sarah Sawyer AU - E. Magda Price AU - Lynette Lau AU - Reem Khan AU - Whiwon Lee AU - Lijia Huang AU - Olga Jarinova AU - Wendy J. Ungar AU - Roberto Mendoza-Londono AU - Martin J. Somerville AU - Kym M. Boycott Y1 - 2022/04/01 UR - http://www.cmajopen.ca/content/10/2/E460.abstract N2 - Background: Genome-wide sequencing has emerged as a promising strategy for the timely diagnosis of rare diseases, but it is not yet available as a clinical test performed in Canadian diagnostic laboratories. We describe the protocol for evaluating a 2-year pilot project, Genome-wide Sequencing Ontario, to offer high-quality clinical genome-wide sequencing in Ontario, Canada.Methods: The Genome-wide Sequencing Ontario protocol was codesigned by the Ontario Ministry of Health, the Hospital for Sick Children in Toronto and the Children’s Hospital of Eastern Ontario in Ottawa. Enrolment of a prospective cohort of patients began on Apr. 1, 2021. Eligible cases with blood samples available for the index case and both parents (i.e., trios) are randomized to receive exome sequencing or genome sequencing. We will collect patient-level data and ascertain costs associated with the laboratory workflow for exome sequencing and genome sequencing. We will compare point estimates for the diagnostic utility and timeliness of exome sequencing and genome sequencing, and we will determine an incremental cost-effectiveness ratio (expressed as the incremental cost of genome sequencing versus exome sequencing per additional patient with a causal variant detected).Interpretation: Findings from this work will provide robust evidence for the diagnostic utility, cost-effectiveness and timeliness of exome sequencing and genome sequencing, and will be disseminated via academic publications and policy briefs. Findings will inform provincial and cross-provincial policy related to the long-term organization, delivery and reimbursement of clinical-grade genome diagnostics for rare disease. ER -