PHARMACOGENOMICS AS PANDORA'S BOX WHAT EARLY SUCCESSES AND SETBACKS ARE TEACH LABS AND PHYSICIANS AS PRECISION MEDICINE MOVES FORWARD Don Rule January 27, 2016
Vision To inform every clinical decision affec<ng every pa<ent everywhere in the world with the best available personalized guidance APRIL 27,2016 2
Data is Overwhelming Cognition 1000 Facts per Decision 100 10 Data Human Cognitive Capacity Source: Daniel R. Masys, M.D., University of Washington 1990 2000 2010 2020 APRIL 27,2016 3
Why Pharmacogenetics? Good Evidence Phenotypes were observed, then genotypes described FDA required tes<ng during drug approval Few genes affect many drugs Many people take drugs 45% of most prescribed drugs have gene<c guidance APRIL 27,2016 4
Average Medications per Patient Medica<on Count 10 9 9 8 8 7 7 6 6 5 4 4 3 3 3 2 0 0 2 4 6 8 10 12 Age in Decades N = 211,555 DECEMBER 16, 2015 5
What is Different About PGx? Typically panel based Once in a life<me OYen complex rela<onship between test result and clinical guidance Requires background in pharmacology as well as gene<cs APRIL 27,2016 6
Multi-Scalar Problem Single SNP OPRM1 118A>G Opioid Efficacy Mul;- SNP MTHFR 1298C & 677T Hyperhomocysteinemia Mul;- Gene Mul;- Allele Mixed Factor II 20210A & Factor V Leiden 1691A rs16947 + rs3892097 + rs1065852 CYP2C9 Phenotype & VKORC1-1639G>A Thrombosis Risk CYP2D6 Haplotype Warfarin Sensi;vity APRIL 27,2016 7
Clinician s Curiosity is Limited by Time What we want to tell doctors What doctors have ;me to read Consider alterna<ves to Codeine #CYP2D6RapidMetabolizer APRIL 27,2016 8
Pharmacogenetics at an Inflection Point Early market driven by entrepreneurial labs CMS was a proponent, offering to pay for evidence Some aggressive labs abused the opportunity Reimbursement was cut Market shiying from lab push to Clinician Pull Surviving labs are finding new business models Early efforts to integrate more deeply with clinical systems APRIL 27,2016 9
The Hype Cycle We are here (I hope) APRIL 27,2016 10
Phase I All you need is a DNA extractor and a Dream Rela<vely cheap and reliable equipment New guidelines from CPIC and others Increased social awareness of Gene<c Medicine Reimbursement cuts in Toxicology force a search for profitable opportuni<es APRIL 27,2016 11
Early Adopters Reference labs capitalizing on the new market Toxicology labs expanding their porbolio to provide more complete services Physician owned labs looking for differen<a<on APRIL 27,2016 12
Early End Users Pain clinics looking to separate between drug seeking and ineffec<ve drugs Psychiatrists looking to reduce the <me to find the right an<depressant Cardiologists working to improve outcomes Generally small prac<ces clinicians that can make an individual decision to order tests APRIL 27,2016 13
Early Successes Millions of tests performed Thousands of clinicians gained first hand experience with benefits Pa<ents eager to find ways to improve their health outcomes Reimbursements were awesome APRIL 27,2016 14
Issues with Phase I Payers unfamiliar and unprepared for pharmacogene<c tes<ng Code stacking Evidence standards inconsistent Equivocal support from the medical community Legal environment unclear Registries were a great idea but the legal boundaries were some<mes difficult to discern Labs tes<ng the limits of the regulatory environment CLIA does not ensure competency in PGx and CAP has high variability among inspec<ons APRIL 27,2016 15
Phase II LCD Armageddon Lab Abuses draw CMS scru<ny Local Coverage Decisions ripple across the country Third party payer clawbacks Single- product labs find difficulty surviving APRIL 27,2016 16
Precision Medicine s Catch 22 CMS seeking gold standard clinical trials Labs do not have Pharma returns Difficult to patent a test based on Genes (see Myriad) Lots of research money for discovery but liile for valida<on Low U<liza<on Insufficient Evidence APRIL 27,2016 17
How to Get Over Your Skis Cowboy salespeople Lack of prep for reimbursement Failing to an<cipate how long reimbursement takes Lower reimbursement rate than an<cipated Poor process for appeal and resubmission Fixed costs that assume permanent high prices APRIL 27,2016 18
Survival Strategies Diversifica<on Consolida<on Emerging payer models APRIL 27,2016 19
Phase III The Inflection Point Consolida<on in the Lab market New evidence emerges ShiY from Lab push to Clinical Pull Evolu<on of payment models APRIL 27,2016 20
Growing Evidence Base Year Results 2015 Genotyped pa<ents saved $1,036 in all medica<ons 2014 Genotyped pa<ents saved $298 over a 4 month period 2013 Genotyping for extreme metabolizers (as a group) reduced costs from $67,064 to $ 20,532 APRIL 27,2016 21
Moving from Opportunity to Threat The opportunity to improve pa<ent care is good but not if there is no business model ShiY to ACO reimbursement implies that ins<tu<ons are paid for quality of care Will not get paid for hospital re- admission Quan<fied quality measures like ADRs The price of tes<ng is rela<vely cheap insurance rela<ve to the cost of re- treatment Labs can offer lower pricing when the provider accepts reimbursement risk and payment is guaranteed APRIL 27,2016 22
New Markets Medica<on Management Review Pharmacy Benefit Management Integrated Delivery Networks To convey thought leadership To lock in pa<ents Pharmacies single point of contact for prescribing APRIL 27,2016 23
Characteristics of Survivors Well trained sales staff Laser- focused on revenue producing customers Adept at finding common ground with payers and providers Moving upscale from small prac<ces APRIL 27,2016 24
Problems with Phase III Once and Done tes<ng does not capture life<me u<lity Test ini<ator owns the data not visible to other providers High deduc<ble plans put financial burden on pa<ents APRIL 27,2016 25
Phase IV Moving Novelty to Standard of Care Pharmacogene<cs deeply embedded into the clinical workflow as drug interac<on tes<ng is now Clinicians easily know the right test for the clinical situa<on at hand Gene<c test results are useful over the life<me of the pa<ent Clinical Decision Support provides insight for the test result IN CONTEXT with other clinical factors APRIL 27,2016 26
Where we Need to Go Reac;ve Preemp;ve Sta;c Dynamic Just- in- Chart Portable Standalone Integrated APRIL 27,2016 27
Implications of the New World Gene<c tes<ng is an integral part of the clinical workflow Tes<ng ra<onal panels (yes, eventually genomes) not gene by gene Decision support is what test to order as well as how to interpret results Test may be ordered for one condi<on but data may be re- used for many other purposes Data must be accessible to your GP as well as your cardiologist and den<st APRIL 27,2016 28
Lifetime Value of PGx Drug adverse event Burden Infant Child Adolescent Young Adult Adult Elderly Lacta<on Pain Contracep<on Polypharmacy Infec<ons Transplanta<on Cancer Psychiatry Addic<on Transplanta<on Cancer Cardiovascular Diabetes Gastroenterology Psychiatry Addic<on Transplanta<on Cancer Autoimmune Diseases Surgery Cardiovascular Diabetes Gatroenterology Psychiatry Neurology Surgery JANUARY 7, 2016 29
Who is Driving the Bus? Provider Driven Ins<tu<ons looking for differen<a<on for s<ckier services ACOs looking for cost control Pharmacies wan<ng to build loyalty Consumer Driven Lab- driven Ask your Doctor strategy to engage informed healthcare consumers to recruit their doctors APRIL 27,2016 30
Who Owns (or Hosts) the Data? Currently Lab has the most complete picture Providers increasingly want to own the data Discrete gene<c data into the EMR Data provides raw materials for Clinical Decision Support Problema<c because of liability issues How do we plan for a full- genome world? Ancillary systems to the EMR (like imaging) that hold genomes Genomic Health Informa<on Exchanges Consumer- focused gene<c repositories (HealthVault on Steroids) APRIL 27,2016 31
Conclusion The early entrepreneurial phase of PGx tes<ng is over killed par<ally by Lab abuse Some labs have survived and thrived even in a changing reimbursement environment The market is moving from suppliers to consumers and that will be very healthy in the long run Surviving in the market will require a higher degree of professionalism The holy grail is deep integra<on into the clinical workflow APRIL 27,2016 32