Original Title: Panel des erreurs innées de l’immunité par séquençage de nouvelle génération: rapport d’évaluation sur le rapatriement d’analyses réalisées hors Québec

Authors' objectives: The mandate of the Réseau québécois de diagnostic moléculaire (RQDM), which includes the Centre québécois de génomique clinique (CQGC), is to address the current and future needs of the health and social services network in the fields of molecular diagnostics and personalized medicine, particularly regarding the diagnosis of rare diseases and oncology. To this end, the RQDM, supported by the Ministry of Health and Social Services (MSSS), has undertaken a comprehensive project to enhance technology, develop, and repatriate analyses performed by next-generation sequencing (NGS). The deployment of this project undoubtedly brings opportunities and risks to the overall NGS service offering and requires thoughtful consideration. At the request of the MSSS, the Institut national d’excellence en santé et en services sociaux (INESSS) is conducting a rapid assessment of the relevance, issues, and, where appropriate, optimal implementation modalities associated with the repatriation of these analyses, from the overall perspective of the Quebec health care system. This report specifically addresses gene panels analyzed by NGS for the molecular diagnosis of inborn errors of immunity (IEI).

Authors' results and conclusions: RESULTS (#1 CLINICAL DIMENSION): Clinicians consulted stress the need for regular updates to the virtual panel composition to keep up with the rapid evolution of new mutations associated with IEI. In the context of atypical or complex phenotypes, some clinicians would like more flexible access to exome data. Furthermore, recommendations have been issued to ensure consistency in prescribing indications and panel gene composition. (#2 ORGANIZATIONAL DIMENSION): In terms of turnaround time for obtaining analysis results, a maximum of 3 months for most virtual panels and 3 weeks for SCID and HLH panels appears acceptable. However, some committee members highlight the lack of genetic counselling resources. Furthermore, access to medical expertise is a major challenge for remote regions. (#3 SOCIOCULTURAL DIMENSION): Ethical issues related to the discovery of genetic variants have been raised, for those concerning patient confidentiality and information protection. Some consulted clinicians for this report suggest that these issues should be evaluated within the RQDM and data specific to Quebec populations should be published, especially in cases of founder effects in certain regions. Mechanisms to ensure equitable access to genetic testing, as well as confidentiality and patient information protection must also be established. (#4 ECONOMIC DIMENSION): The efficiency of whole-genome sequencing for the molecular diagnosis of IEI is unknown. Over the first three years, repatriating analyses performed outside of Quebec could generate savings of $ 0.972 million ($ 0.875 million to $1.07 million) or $0.353 million ($0.318 million to $0.388 million) if analyses were performed using WES or whole genome sequencing (WGS) data, respectively. Hence, the analysis through virtual panels using WES data would be the most affordable option. The costs of bioinformatics tools (licenses, data storage) as well as requests for other IEI panels in case of negative results could reduce these savings. CONCLUSION: This state of knowledge is based on a rapid review of scientific and gray literature, as well as contextual information and experiential knowledge. It aims to provide guidance to the MSSS in its decision to repatriate genetic analyses for the diagnosis of IEI. While no major concerns were identified during this exercise, uncertainties related to available resources and service organization in Quebec were highlighted and should be explored to ensure optimal implementation.

Authors' methods: The process involves a rapid review of scientific and gray literature, a budgetary impact analysis, and consultations with Quebec clinicians. Only documents presenting synthesized data or recommendations related to the use of NGS for IEI diagnosis were considered. INESSS established an advisory committee where members expressed their views on the various issues associated with the proposed analysis repatriation. The final conclusions are based on the triangulation of scientific data, positions taken by major consulted scientific societies, contextual information, and experiential knowledge.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/panel-des-erreurs-innees-de-limmunite-par-sequencage-de-nouvelle-generation.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/panel-des-erreurs-innees-de-limmunite-par-sequencage-de-nouvelle-generation.html

English language abstract: An English language summary is available

Publication Type: Other

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)