pharmacogenomics as pandora's box · 1000 10 100 1990 2000 2010 2020 human cognitive capacity...
TRANSCRIPT
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
1000 Fa
cts
per D
ecis
ion
10
100
1990 2000 2010 2020
Human Cognitive Capacity
Source: Daniel R. Masys, M.D., University of Washington
Data
Data is Overwhelming Cognition
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
N = 211,555
3 3 3 4
5 6
7 8
9 9
7
0
2
4
6
8
10
0 2 4 6 8 10 12
Med
ica<
on Cou
nt
Age in Decades
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 Factor II 20210A & Factor V Leiden 1691A
Thrombosis Risk
Mul;-‐Allele rs16947 + rs3892097 + rs1065852
CYP2D6 Haplotype
Mixed CYP2C9 Phenotype & VKORC1 -‐1639G>A
Warfarin Sensi;vity
APRIL 27,2016 7
Clinician’s Curiosity is Limited by Time What we want to tell doctors
APRIL 27,2016 8
What doctors have ;me to read
Consider alterna<ves to Codeine #CYP2D6RapidMetabolizer
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
APRIL 27,2016 10
We are here (I hope)
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
Insufficient Evidence
Low U<liza<on
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
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
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
Lifetime Value of PGx
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