Kym Boycott, CHEO Diagnostic Breakthroughs: From Newborn Screening to Next Gen Sequencing
1) Access to appropriate diagnostic testing for rare diseases can be challenging, with specialists often taking 3-6 years to diagnose patients and 40% receiving multiple misdiagnoses. Genome sequencing is helping diagnose more patients, with over 200,000 clinically sequenced worldwide. 2) Guidelines published in 2015 recommend clinical genome sequencing be offered as a first-tier test to help speed diagnosis. By 2017, sequencing was diagnosing 33-47% of rare disease patients. 3) Efforts are underway in Canada to improve access to genomic sequencing, including developing clinical implementation plans, data governance frameworks, and technical specifications to establish genomic sequencing services across provinces. The goal is to enable sequencing for rare disease diagnosis and precision health nationwide.
Kym Boycott, CHEO Diagnostic Breakthroughs: From Newborn Screening to Next Gen Sequencing
- 1. Diagnostic Breakthroughs: the path to access to the right test at the right time Kym Boycott, MD, PhD, FRCPC, FCCMG Professor of Pediatrics, University of Ottawa
- 2. Unmet Clinical Need 3-5 Specialists (>11 for 10%) 3-6 Years for a diagnosis 40% Received >3 misdiagnoses $15,000 ($8,000-$23,000) Cost per patient Access to appropriate testing can be challenging Our understanding of the causes of RDs is incomplete
- 3. So along comes the best test we’ve ever had… 30% Diagnosed 70% Undiagnosed More than 200,000 rare disease patients now clinically sequenced world-wide Diagnostic Breakthrough Clinical genome-wide sequencing
- 4. CCMG guidelines: Diagnostic translation Journal of Medical Genetics 2015
- 5. 5,016,322 4,330,206 1,165,903 1,356,836 14,411,424 8,421,698 525,073 964,693 772,238 154,750 40,333 44,445 38,650 Statistics Canada estimates Q4 2018 Canada: 37,242,571 Access to clinical exome sequencing in 2018 800/yr 0/yr 50/yr30/yr 200/yr 100/yr 30/yr 50/yr
- 10. 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.45 0.5 2013 2014 2015 2016 2017 OddsofDiagnosis WES/WGS á 16%/year CMA â 14%/year Available to the right patient
- 11. Standard diagnostic trajectory Standard diagnostic trajectory First Tier WES WES Second Tier WES At the right time 33% 23% 47% Diagnostic Yield 200 families ? %
- 12. Access for all Canadians Clinical implementation for RD precision health
- 13. GWS for RD diagnosis Diagnostic utility 2013 Canadian best practices 2015 Data governance framework 2018 Provincial consentprocess 2018 Technical Specs 2019 GWS service Ontario Eligibility 2016
- 14. The risk for rare diseases
- 15. Matchmaker Exchange Data from >100,000 patients from >4000 contributors from >84countries Global Collaboration
- 16. The opportunity
- 17. Emerging technologies Coding Splicing Regulatory Mosaicism Rearrangements Coding Other Genome sequencing Transcriptome Deep sequencing Metabolomics Lipidomics Methylome
- 18. A means to diagnose most RDs Boycott at al., 2017: Am J Hum Genet 100; 695–705