Positioning whole exome sequencing in the diagnostic pathway for rare disease to optimise utility: a protocol for an observational cohort study and an economic evaluation
Introduction Despite the superior diagnostic performance of exome and genome sequencing compared with conventional genetic tests, evidence gaps related to clinical utility and cost effectiveness have limited their availability in routine clinical practice in many jurisdictions. To inform adoption an...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2022-10-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/10/e061468.full |
| _version_ | 1811344446172692480 |
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| author | Deborah A Marshall Francois Bernier Christine Michaels-Igbokwe Kym M Boycott Robin Z Hayeems Taila Hartley |
| author_facet | Deborah A Marshall Francois Bernier Christine Michaels-Igbokwe Kym M Boycott Robin Z Hayeems Taila Hartley |
| author_sort | Deborah A Marshall |
| collection | DOAJ |
| description | Introduction Despite the superior diagnostic performance of exome and genome sequencing compared with conventional genetic tests, evidence gaps related to clinical utility and cost effectiveness have limited their availability in routine clinical practice in many jurisdictions. To inform adoption and reimbursement policy, this protocol provides a chain of evidence approach to determining the diagnostic utility, clinical utility and cost-effectiveness of whole exome sequencing (WES) from seven medical genetic centres in two Canadian provinces.Methods and analysis Using a multicentre observational cohort design, we will extract data specific to the pre-WES diagnostic pathway and 1-year post-WES medical management from electronic medical records for 650 patients with rare disease of suspected genetic aetiology who receive WES. The date from the clinical record will be linked to provincial administrative health database to capture healthcare resource use and estimate costs. Our analysis will: (1) define and describe diagnostic testing pathways that occur prior to WES among patients with rare disease, (2) determine the diagnostic utility of WES, characterised as the proportion of patients for whom causative DNA variants are identified, (3) determine the clinical utility of WES, characterised as a change in medical management triggered by WES results, (4) determine the pattern and cost of health service utilisation prior and 1 year following WES among patients who receive a diagnosis, do not receive a diagnosis, or receive an uncertain diagnosis and (5) estimate the cost-effectiveness of WES compared with conventional diagnostic testing pathways, measured by the incremental cost per additional patient diagnosed by WES using simulation modelling.Ethics and dissemination This protocol was approved by Clinical Trials Ontario (CTO-1577) and research ethics boards at the University of Calgary (REB18-0744 and REB20-1449) and University of Alberta (Pro0009156). Findings will be disseminated through academic publications and policy reports. |
| first_indexed | 2024-04-13T19:47:28Z |
| format | Article |
| id | doaj.art-aec2df602453457092d42a23f8299358 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-04-13T19:47:28Z |
| publishDate | 2022-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-aec2df602453457092d42a23f82993582022-12-22T02:32:40ZengBMJ Publishing GroupBMJ Open2044-60552022-10-01121010.1136/bmjopen-2022-061468Positioning whole exome sequencing in the diagnostic pathway for rare disease to optimise utility: a protocol for an observational cohort study and an economic evaluationDeborah A Marshall0Francois Bernier1Christine Michaels-Igbokwe2Kym M Boycott3Robin Z Hayeems4Taila Hartley5Cummings School of Medicine, University of Calgary, Calgary, Alberta, CanadaDepartment of Medical Genetics, Alberta Children`s Hospital, Calgary, Alberta, CanadaCummings School of Medicine, University of Calgary, Calgary, Alberta, CanadaDepartment of Genetics, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, CanadaChild Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, Ontario, CanadaDepartment of Genetics, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, CanadaIntroduction Despite the superior diagnostic performance of exome and genome sequencing compared with conventional genetic tests, evidence gaps related to clinical utility and cost effectiveness have limited their availability in routine clinical practice in many jurisdictions. To inform adoption and reimbursement policy, this protocol provides a chain of evidence approach to determining the diagnostic utility, clinical utility and cost-effectiveness of whole exome sequencing (WES) from seven medical genetic centres in two Canadian provinces.Methods and analysis Using a multicentre observational cohort design, we will extract data specific to the pre-WES diagnostic pathway and 1-year post-WES medical management from electronic medical records for 650 patients with rare disease of suspected genetic aetiology who receive WES. The date from the clinical record will be linked to provincial administrative health database to capture healthcare resource use and estimate costs. Our analysis will: (1) define and describe diagnostic testing pathways that occur prior to WES among patients with rare disease, (2) determine the diagnostic utility of WES, characterised as the proportion of patients for whom causative DNA variants are identified, (3) determine the clinical utility of WES, characterised as a change in medical management triggered by WES results, (4) determine the pattern and cost of health service utilisation prior and 1 year following WES among patients who receive a diagnosis, do not receive a diagnosis, or receive an uncertain diagnosis and (5) estimate the cost-effectiveness of WES compared with conventional diagnostic testing pathways, measured by the incremental cost per additional patient diagnosed by WES using simulation modelling.Ethics and dissemination This protocol was approved by Clinical Trials Ontario (CTO-1577) and research ethics boards at the University of Calgary (REB18-0744 and REB20-1449) and University of Alberta (Pro0009156). Findings will be disseminated through academic publications and policy reports.https://bmjopen.bmj.com/content/12/10/e061468.full |
| spellingShingle | Deborah A Marshall Francois Bernier Christine Michaels-Igbokwe Kym M Boycott Robin Z Hayeems Taila Hartley Positioning whole exome sequencing in the diagnostic pathway for rare disease to optimise utility: a protocol for an observational cohort study and an economic evaluation BMJ Open |
| title | Positioning whole exome sequencing in the diagnostic pathway for rare disease to optimise utility: a protocol for an observational cohort study and an economic evaluation |
| title_full | Positioning whole exome sequencing in the diagnostic pathway for rare disease to optimise utility: a protocol for an observational cohort study and an economic evaluation |
| title_fullStr | Positioning whole exome sequencing in the diagnostic pathway for rare disease to optimise utility: a protocol for an observational cohort study and an economic evaluation |
| title_full_unstemmed | Positioning whole exome sequencing in the diagnostic pathway for rare disease to optimise utility: a protocol for an observational cohort study and an economic evaluation |
| title_short | Positioning whole exome sequencing in the diagnostic pathway for rare disease to optimise utility: a protocol for an observational cohort study and an economic evaluation |
| title_sort | positioning whole exome sequencing in the diagnostic pathway for rare disease to optimise utility a protocol for an observational cohort study and an economic evaluation |
| url | https://bmjopen.bmj.com/content/12/10/e061468.full |
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