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. 2022 May 24;10(2):E460-E465.
doi: 10.9778/cmajo.20210272. Print 2022 Apr-Jun.

Comparing genome sequencing technologies to improve rare disease diagnostics: a protocol for the evaluation of a pilot project, Genome-wide Sequencing Ontario

Robin Z Hayeems  1 , Christian R Marshall  2 , Meredith K Gillespie  2 , Anna Szuto  2 , Caitlin Chisholm  2 , Dimitri J Stavropoulos  2 , Viji Venkataramanan  2 , Kate Tsiplova  2 , Sarah Sawyer  2 , E Magda Price  2 , Lynette Lau  2 , Reem Khan  2 , Whiwon Lee  2 , Lijia Huang  2 , Olga Jarinova  2 , Wendy J Ungar  2 , Roberto Mendoza-Londono  2 , Martin J Somerville  2 , Kym M Boycott  2
Affiliations

Comparing genome sequencing technologies to improve rare disease diagnostics: a protocol for the evaluation of a pilot project, Genome-wide Sequencing Ontario

Robin Z Hayeems et al. CMAJ Open. .

Abstract

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.

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Conflict of interest statement

Competing interests: The authorship group has received funding from the Ontario Ministry of Health and Genome Canada to examine the implementation of genome-wide sequencing in Ontario. Dimitri Stavropoulos has equity in PhenoTips. Wendy Ungar chairs the Ontario Genetics Advisory Committee, is a member of the Ontario Health Technology Assessment Committee, and receives funding from the Pharmaceutical Research and Manufacturers of America Foundation and honoraria from the Taiwan Center for Drug Evaluation. Robin Hayeems is a member of the Ontario Genetics Advisory Committee. Robin Hayeems, Martin Somerville and Kym Boycott are members of the Provincial Genetics Advisory Committee.

Figures

Figure 1:
Figure 1:
Genome-wide Sequencing Ontario harmonized, multi-institutional model for delivering genome-wide sequencing (GWS). CHEO = The Children’s Hospital of Eastern Ontario, GS = genome sequencing, ES = exome sequencing, SickKids = The Hospital for Sick Children.
See this image and copyright information in PMC

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