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