Emerging and New
Technologies
• Debra G.B. Leonard, MD, PhD,
FCAP, Weill Cornell Medical
College, New York Presbyterian
Hospital
• Patricia Deverka, MD, MS, MBE,
Center for Medical Technology
Policy
Debra G.B. Leonard, MD, PhD, FCAP
Pathologists and Genomic Medicine
May 8, 2012
Objectives
• Pathologists have an opportunity to lead in
Genomic Medicine and why this is important
• Today’s challenges to widespread adoption
of Genomic Medicine
• How Genomic Medicine affects all
pathologists
• The College’s Advocacy efforts to support
pathologists in Genomic Medicine
Understanding of the Human Genome Combined with
Sequencing Technology Advances are Moving Us
Toward Genomic Medicine
Human Genome Project
Completed 2003
1 Generic Genome
Technology & Knowledge Advances
Individual Patient Genomes
Direct Patient Care
Improve Outcomes
Genomic Medicine is made
possible by ability to analyze
individual patient genomes
Genomic Medicine
(Personalized Medicine)
A Cancer Genomics Case: Diagnosis & Treatment
• 78 yr. old Caucasian male with base of tongue mass
• Mass resected, followed by adjuvant radiation
• 1.5 cm poorly differentiated adenocarcinoma with
micropapillary & mucinous features;
• 3/21 neck LNs positive;
• 2+ EGFR IHC staining
• Lung nodules developed
• Tx: Erlotinib (EGFR inhibitor)
• Continued growth on therapy
• Consent for genome & transcriptome
analysis of lung nodule biopsy
(Jones et al. Genome Biology 2010, 11:R82)
A Cancer Genomic Case: Genomic-Based Treatment
• RB1 & PTEN loss associated with EGFR inhibitor
(gefitinib) resistance c/w erlotinib failure
• Up regulation of RET and RET signaling pathway
• Treated with sunitinib (RET inhibitor) with lung
nodule reduction & stable disease for 4 months
• Switched to a multi-kinase inhibitor (sorafenib) with
stable disease for 3 months
• Repeat genomic analysis of met suggested need for
combination treatment with RET, EGFR and mTOR
inhibitor therapy; not done
Genomic Analysis has the potential to individualize
treatment for each cancer to improve response
(Jones et al. Genome Biology 2010, 11:R82)
Genomic Medicine is Driving a Strong Global
Molecular Diagnostics Market with Estimated Annual
Growth Rate of 13.6%
World Market for Molecular Diagnostics, 2009-2015E
Source: ‘Valuation of Carried Intangible Assets’, Acuity Technology Management, June 2011
USD MM
Genetics & Oncology Show Highest Growth with
Continued Growth in Infectious Diseases
North American Genetic, Oncology and Infectious Disease Market, 2009–2015E
2,667
(13%)
2,354
(13%)
2,080
(13%)
1,839
(13%)
1,628
(13%)
1,444
(13%)
1,282
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.
Genomic Analysis by Next Generation Sequencing is
Being Used in Molecular Pathology Practice Today
Research will increase
clinical use
Past and Continuing
Molecular Pathology
Tests
Genomic Analysis:
Clinically Useful Now
Genomic Analysis:
Research & Future
Potential
Single/Few Mutations
Gene Panels
Genome
Single Gene/Pathogen
Exome
Transcriptome
Few Genes/Pathogens
= Genomic Analysis by Next Gen Sequencing
Next Generation Sequencing is the newest Molecular Pathology
technology and is being used now
Some Molecular Pathology Tests Will Move to Next Generation
Sequencing While Others Will Remain on Current Platforms
Molecular Pathology
Current Molecular Pathology
Testing Examples
Genomic Analysis
• Viral Loads
• Bone Marrow Engraftment
Analysis
• Deafness Genetic Testing
• EGFR Mutations
• KRAS Mutations
• BRAF Mutations
Gene Panels
Exome
• Cancer
• Cancer
• Specific
inherited
disorders
• Unidentified
inherited
disorders
Opportunities Exist for ALL Pathologists to Play Key
Roles Within Genomic Medicine
Pre-Analytical
Sequence Data Generation
Sequence Data Interpretation
All Pathologists
Molecular Pathologists,
Molecular Geneticists,
Industry & Others with
strong molecular biology
or genetics knowledge
Reporting & Billing
All Pathologists
Clinical Consultation
The Cost of Genome Sequencing Is Decreasing Rapidly
and Driving Clinical Adoption of Genomic Analysis
Cost per Genome Data Generation, 2001 – 2011
Cost for genome sequence data generation today is <$3,000
Source: National Human Genome Research Institute
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
Opportunities Exist for ALL Pathologists to Play Key
Roles Within Genomic Medicine
Pre-Analytical
Sequence Data Generation
Sequence Data Interpretation
Reporting & Billing
Clinical Consultation
What is the landscape
for ALL Pathologists in
the Pre-Analytical &
Clinical Consultation
Phases for Genomic
Testing?
Clinical Decision Support Tools Can Assist ALL
Pathologists with the Pre-analytical and Clinical
Consultations for Genomic Medicine
Sequence
Analysis
Source: Grail Analysis
Variant
Database
Clinical
Decision
Support
Speed of Clinical Adoption Hinges on Several Factors
Decreasing
Costs
• Cost of genome analysis is rapidly decreasing
• Sequencing instruments now are clinically affordable
Increasing
Speed
• Can generate sequencing data in 10-36 hours
• Clinically relevant TAT available today for data generation
Bioinformatics
• Need clinical quality databases and software tools
• Pathologists must participate in development
Clinical
Usefulness
• Genomic Analysis is in clinical use now (small but growing)
• Research/discovery will increase clinical applications
Payment
Uncertainty
• Currently, no specific CPT codes exist for Genomic Analysis
• Payers do not understand Genomic Analysis
Regulatory
Uncertainty
• Federal regulatory uncertainty today
• Quality standards being led by CAP with AMP & ACMG
Current GA Reporting and Payment Environment is
Uncertain
Pre-Analytical
Sequence Data Generation
Sequence Data Interpretation
Reporting & Billing
Clinical Consultation
• 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
Current GA Regulatory Environment is Uncertain
Pre-Analytical
Sequence Data Generation
Sequence Data Interpretation
Reporting & Billing
Clinical Consultation
• 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
Pathologists Have an Opportunity to Lead the Medical
Community in Genomic Medicine
• No single medical specialty is well informed about
Genomic Medicine
• Pathologists have the opportunity to be seen as
thought leaders in Genomic Medicine
• While Next Gen technology is rapidly advancing, the
growth of the genomics knowledge base will result in
a slow evolution of clinical applications
• Pathologists must have a genomics advocacy voice
to be seen as leaders in Genomic Medicine
CAP policy and advocacy initiatives preserve our role
and assert our leadership in Genomic Medicine…
New Molecular Pathology Codes
CAP LDT Oversight Proposal
Removing Barriers to Consulting
with Patients on Test Results
Preserving Scope of Practice
Resisting Gene Patents
• 100 new test-specific CPT
codes
• CAP at the table on how to
regulate LDTs, including
genomic tests
• CAP advocating to knock
down laws that impede
pathologists from releasing
pathology results and
consulting with patients
• CAP is blocking state laws
that encroach on
pathologists’ role as a
physician
• CAP is a plaintiff in the
BRCA lawsuit against Myriad