pathology perspectives on clinical genomics · pathology perspectives on clinical genomics debra...
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![Page 1: Pathology Perspectives on Clinical Genomics · Pathology Perspectives on Clinical Genomics Debra G.B. Leonard, MD, PhD, FCAP Weill Cornell Medical College May 3, 2012 . Overview of](https://reader036.vdocuments.us/reader036/viewer/2022062920/5f0252697e708231d403b232/html5/thumbnails/1.jpg)
Pathology Perspectives on Clinical Genomics
Debra G.B. Leonard, MD, PhD, FCAP
Weill Cornell Medical College
May 3, 2012
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Overview of Presentation
• IOM Report on Recommended Pathway for Omics Test Evaluation Framework
• College of American Pathologists Evaluation of Genomics
• Genomics from a Molecular Pathologist’s Perspective
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Recommended Framework for Evaluation of Omics Tests from Discovery to Test
Validation and Clinical Utility Assessment
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Understanding of the Human Genome Combined with Sequencing Technology Advances are Moving Us Toward Genomic Medicine
Human Genome Project
Completed 2003 1 Generic Genome
Direct Patient Care
Improved Outcomes Genomic Medicine is made
possible by ability to analyze individual patient genomes Genomic Medicine
(Personalized Medicine)
Individual Patient Genomes
Technology & Knowledge Advances
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Genomic Medicine is Driving a Strong Global Molecular Diagnostics Market with Estimated Annual Growth of 13.6%
2,917 3,304 3,748 4,257
4,841 5,506
6,268
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
2009 2010 2011E 2012E 2013E 2014E 2015E
USD
MM
World Market for Molecular Diagnostics, 2009-2015E
Source: ‘Valuation of Carried Intangible Assets’, Acuity Technology Management, June 2011
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857 947
(10%)
1,048
(11%)
1,159
(11%)
1,284
(11%)
1,423
(11%)
1,577
(11%)
211 248
(17%)
293 (18%)
346 (18%)
408 (18%)
481 (18%)
568 (18%)
214
248 (16%)
288 (16%)
334 (16%)
388 (16%)
450 (16%)
522 (16%)
0
500
1,000
1,500
2,000
2,500
2009 2010 2011E 2012E 2013E 2014E 2015E
Genetics
Oncology
Infectious
Diseases
Genetics & Oncology Show Highest Growth with Continued Growth in Infectious Diseases in North American Market
USD
MM
1,282
1,444 (13%)
1,628 (13%)
1,839 (13%)
2,080 (13%)
2,354 (13%)
2,667 (13%)
Source: ‘Valuation of Carried Intangible Assets’, Acuity Technology Management, June 2011; The Future Of Molecular Diagnostics: Innovative
technologies driving market opportunities in personalized medicine. Business Insights report No: BI00021-012. 23 June 2010.
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The Cost of Genome Sequencing Is Decreasing Rapidly and Driving Clinical Adoption of Genomic Analysis
Source: National Human Genome Research Institute
Cost per Genome Data Generation, 2001 – 2011
$1,000
$10,000
$100,000
$1,000,000
$10,000,000
$100,000,000
Oct
-01
Ap
r-0
2
Oct
-02
Ap
r-0
3
Oct
-03
Ap
r-0
4
Oct
-04
Ap
r-0
5
Oct
-05
Ap
r-0
6
Oct
-06
Ap
r-0
7
Oct
-07
Ap
r-0
8
Oct
-08
Ap
r-0
9
Oct
-09
Ap
r-1
0
Oct
-10
Ap
r-1
1
Oct
-11
Cost for genome sequence data generation today is <$3,000
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Advances in Sequencing Technology is Driving Adoption of Clinical Genomic Analysis in Molecular Pathology Laboratories
Clinical Genomics is possible today & technology continues to advance
ABI
Hundreds
$ 250,000
Years
NA
Sequencers
Instrument Price
Time
Output
1st Genome
Genomic Analysis
Single
Genes
HiSeq
One
$ 750,000
Weeks
~50 Gb
Research/
Clinical
Gene Panels,
Exome,
Genome
TIME
Clinically Relevant
Cost & TAT
Ion Proton
(Q4 2012)
One
Unknown
8 hours
50 Gb
Gene
Panels to
Genome
MiSeq Ion Torrent
(Q1 2012)
One One
$ 125,000+ $ 75,000
27 hours 8 hours
2 Gb 1 Gb
Gene
Panels
Gene
Panels
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Genomic Testing by Next Gen Sequencing is Being Used in Molecular Pathology Practice Today
Next Gen Sequencing is the newest Molecular Pathology technology and is being used now
Single Gene/Pathogen
Few Genes/Pathogens
Single/Few Mutations
Past and Continuing
Molecular Pathology
Tests
Gene Panels
Exome
Genomic Analysis:
Clinically Useful Now
Transcriptome
Genome
Genomic Analysis:
Research & Future
Potential
Research will increase
clinical use
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Some Molecular Tests Will Move to Next Generation Sequencing While Others Will Remain on Current Platforms
Current Molecular Pathology
Testing Examples
Molecular Pathology
Genomic Analysis
• Cancer
• Specific
inherited
disorders
• Cancer
• Unidentified
inherited
disorders
• Viral Loads
• Bone Marrow Engraftment
Analysis
• Deafness Genetic Testing
• EGFR Mutations
• KRAS Mutations
• BRAF Mutations
Gene Panels Exome
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Opportunities Exist for ALL Pathologists to Play Key Roles Within Genomic Medicine
All Pathologists
All Pathologists
Pre-Analytical
Sequence Data Interpretation
Reporting & Billing
Clinical Consultation
Sequence Data Generation Molecular Pathologists,
Molecular Geneticists, Industry & Others with
strong molecular biology
or genetics knowledge
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Early Adopters Identify Clinical Grade Databases and Bioinformatics Tools as a High Priority Need
• Clinical Database(s):
o Require significant time & money
o Need to define quality & submission standards
o Need to define access & IP issues
• Software Tools for Interpretation and Clinical Usefulness:
o Require significant time & money
o Many software tools being developed
o No interoperability standards
o Will facilitate role for ALL pathologists in Genomic Medicine
Pathologists should be at the table in the development of bioinformatics tools & should learn to use tools as developed
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Opportunities Exist for ALL Pathologists to Play Key Roles Within Genomic Medicine
What is the landscape for ALL Pathologists in the Pre-Analytical & Clinical Consultation Phases for Genomic Testing?
Pre-Analytical
Sequence Data Interpretation
Reporting & Billing
Clinical Consultation
Sequence Data Generation
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Clinical Decision Support Tools Can Assist ALL Pathologists with the Pre-analytical and Clinical Consultations for Genomic Medicine
Biobase
GeneGo
Cartagenia
Omicia
CollabRx
Ingenuity
Interactive Biosoftware
Reactome
Ariadne
My Cancer Genome
Variant Database
Sequence Analysis
Clinical Decision Support
Source: Grail Analysis
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Bioinformatics • Need clinical quality databases and software tools
• Pathologists must participate in development
Speed of Clinical Adoption Hinges on Several Factors
Decreasing
Costs
• Cost of genome analysis is rapidly decreasing
• Sequencing instruments now are clinically affordable
• Genomic Analysis is in clinical use now (small but growing)
• Research/discovery will increase clinical applications
Clinical
Usefulness
Payment
Uncertainty
• Currently, no specific CPT codes exist for Genomic Analysis
• Payers do not understand Genomic Analysis
Increasing
Speed
• Can generate sequencing data in 10-36 hours
• Clinically relevant TAT available today for data generation
Regulatory
Uncertainty
• Federal regulatory uncertainty today
• Quality standards being led by CAP with AMP & ACMG
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Current GA Reporting and Payment Environment is Uncertain
• No IT standards for reporting in LIS, EHR & PHR
• Interoperability standards
• Terminology standards
• Molecular CPT Codes under revision
• No GA CPT Codes available
• Payers do not understand GA
• Early adopters negotiating coverage & reimbursement with each payer for each patient by early adopters
Pre-Analytical
Sequence Data Interpretation
Reporting & Billing
Clinical Consultation
Sequence Data Generation
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Current GA Regulatory Environment is Uncertain
• FDA held meeting to understand early clinical users needs & concerns
• No FDA position/guidance
• No CLIA standards for GA
• CAP Next Generation Sequencing (NGS) Work Group
o NGS Checklist questions
o PT Exchange
Pre-Analytical
Sequence Data Interpretation
Reporting & Billing
Clinical Consultation
Sequence Data Generation
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Pathologists Have an Opportunity to Lead the Medical Community in Genomic Medicine
• No single medical specialty is well informed about Genomic Medicine
• Pathologists have an opportunity to be leaders in Genomic Medicine as another diagnostic testing modality
• While genomic technology is rapidly advancing, the discovery process for clinical genomics applications will be an evolution rather than a revolution
• Pathologists can lead in the application of genomic testing as evidence for clinical applications and utility develops
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Thoughts on Genomics from a Molecular Pathologist
• Genomics is the next adventure for Molecular Pathology
• Need quality guidelines for data generation and bioinformatics
• Standards hard to develop when everyone still learning ad technology changing so rapidly
• Basic accreditation standards developed for 2012 (CAP, ACMG, AMP) and will evolve as we develop standards/guidelines
• PT is complicated but is coming (CAP)
• Appropriate billing codes needed
• Need to train next generation for genomics
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Many Thanks to IOM & CAP Committee Colleagues
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