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  

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Human Cognitive Capacity

Source:  Daniel  R.  Masys,  M.D.,  University  of  Washington  

Data

Data is Overwhelming Cognition

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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  

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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  

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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  

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Clinician’s Curiosity is Limited by Time   What  we  want  to  tell  doctors  

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  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  

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The Hype Cycle

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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  

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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  

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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  

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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  

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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  

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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  

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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  

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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  

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Survival Strategies   Diversifica<on  

  Consolida<on     Emerging  payer  models  

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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  

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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  

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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  

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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  

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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  

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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  

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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  

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Where we Need to Go Reac;ve   Preemp;ve  

Sta;c   Dynamic  

Just-­‐in-­‐Chart   Portable  

Standalone   Integrated  

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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  

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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  

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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)  

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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  

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