Susan  Estabrooks  Hahn,  MS,  CGC  John  P.  Hussman  Ins�tute  for  Human  Genomics,  University  of  Miami,    Miller  School  of  Medicine    

 

 

Implica�ons  of  Genome  Sequencing  on  Public  Health:  Promise  and  Pi�alls  

Objec�ves  � Cite  the  current  uses  of  genome  technology  in  public  health  

� Describe  the  ways  next  generation  sequencing  (NGS)  may  benefit  public  health  in  the  future  

� Discuss  the  challenges  to  responsible  and  effective  implementation  of  NGS    

High  hopes  for  genomics  impact  on  public  health…  �  “Combined  with  our  advancing  understanding  of  genes  and  disease,  whole  genome  sequencing  is  set  to  change  the  current  clinical  and  public  health  practice  by  enabling  more  accurate,  sophisticated,  and  cost  effective  genetic  testing.”  

�  Phg  foundation  –  October  2011  

�  “Eventually  genomics  will  help  to  change  the  face  of  public  health  by  focusing  interventions  on  individuals  and  groups  who  will  benefit  the  most  from  behavioral  modifications,  drug  therapies,  and  other  forms  of  interventions.  I  predict  that  genomics  will  become  a  fundamental  tool  of  public  health  in  the  21st  century.”  

�  Muin  Khoury  -­‐  Director,  Office  of  Public  Health  Genomics  

What  is  public  health?  �  Public  health  is  the  science  of  protecting  and  improving  the  health  of  the  population  

�  Activities  to  achieve  this  include:  �  educational  programs  �  recommending  policies    �  administering  services  �  conducting  research    

� Misconceptions:  �  Not  all  efforts  are  aimed  at  the  population  at  large    

�  improving  individual  health  is  important  for  the  better  health  of  the  population  at  large  

�  Centers  for  Disease  Control  and  Prevention  (CDC)  �  Responsible  for  protecting  America’s  public  health  

Public  Health  Genomics  �  “Public  health  genomics  is  a  multi-­‐disciplinary  field  that  focuses  on  the  effective  and  responsible  translation  of  genetic  information  and  technology  for  the  benefit  of  population  health.”  OHPG    

� Most  efforts  are  state  driven  and  can  vary  significantly  in  approach  

 

�  Federal  Effort:    �  The  Office  of  Public  Health  Genomics  (OPHG)  promotes  the  integration  of  genomics  into  public  health  research,  policy,  and  practice  to  prevent  disease  and  improve  the  health  of  all  people.  http://www.cdc.gov/genomics/  

Current  Applica�ons  of  Genomics  to  Public  Health  �  State  Driven  

�  Newborn  Screening  �  Clinical  services  for  rare  genetic  disease    �  Public  and  provider  education  �  Local  research,  often  support  by  federal  government  

�  Federal  Efforts  �  Surgeon  General’s  Family  Health  History          Initiative  �  EGAPP  (Evaluation  of  Genomic  Applications  in  Practice  and  Prevention)  

�  Provide  funding  for  state  driven  pilot  projects  �  Develop  and  provide  training  and  educational  materials  and  assistance  about  public  health  genomics  

2013  OPHG  Efforts  to  Support  the  Use  of  Genomics  in  Public  Health  by  OPHG  �  Integrate  evidence-­‐based  genomic  applications  into  public  health  

programs  �  implement  demonstration  projects  with  selected  health  departments  �  develop  public  health  “surveillance  indicators”  for  evidence-­‐based  genomic  

applications  to  track  progress  and  evaluate  population  impact  �  develop  a  state  public  health  “genomics  toolkit”  to  provide  information  for  

public  health  programs  on  how  to  implement  evidence-­‐based  applications  

�  Develop  and  provide  communications,  publications,  training,  policy  and  technical  assistance  about  public  health  genomics  to  various  audiences  

�  Supports  EGAPP  –  Evaluation  of  Genomic  Applications  in  Practice  and  Prevention  

 

http://www.cdc.gov/genomics/  

Public  Health  Genomics  Challenge  �  In  industrialized  nations,  complex  disorders  are  the  most  

important  threats  to  population  health  �  Making  the  leap  from  newborn  screening  and  rare  disease  programs  to  address  common  complex  disease  is  the  greatest  challenge  for  public  health  genomics  

 Dreambuildercoachingprogram.com

Tackling  Complex  Disease  with  Public  Health  Ini�a�ves  �  Family  Health  History  Initiative  

�  Minimal  impact  thus  far  �  Awareness  campaigns  made  little          impact  on  physician  and  public          awareness  and  motivation  �  Easy  for  physicians  to  stick  their          head  in  the  sand    

�  EGAPP  Recommendations  �  Useful,  but  limited  impact  

�  OPHG  budget  drastically  cut  

�  We  NEED  something  better    

Dreambuildercoachingprogram.com

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Tackling  Complex  Disease  with  Public  Health  Ini�a�ves  

       

Is  sequencing  the    answer?  

Dreambuildercoachingprogram.com

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Poten�al  Benefits  of  Sequencing  to  Public  Health  

Improved  preven�on  and  targeted  treatment  for  the  popula�on  �  Currently,  about  1%  of  the  population  carries  a  mutation  that  greatly  predisposes  them  to  a  serious,  but  eminently  preventable  disease  –  James  Evans,  ACMG  statement  

�  Utility  for  disease  prediction  and  for  making  treatment  decisions  is  projected  to  increase  steadily  

 

�  Sequencing  enables  the  ability  to  provide  a  broad  spectrum  of  genomic  information  at  once,  versus  one  utility  at  a  time    �  i.e.  lifetime  access  to  personal  genomic  information  vs.  necessitating  a  la  carte  testing  

Reduc�on  of  Health  Dispari�es  Related  to  Use  of  Genomic  Informa�on  �  Sequencing  conducted  in  absence  of  public  health  input  may  further  magnify  disparities  due  to  access  issues  caused  by:  �  cost    �  lack  of  motivated  and  knowledgeable            clinicians    �  receptiveness  of  patients  due            to  misconceptions  or  lack  of  awareness  �  incomplete  data  due  to  lack  of            diverse  research  participations    

Reduc�on  of  Health  Dispari�es  Related  to  Use  of  Genomic  Informa�on  

 

�  A  public  health  focus  that  facilitates  equitable  access  to  sequencing  by  addressing  issues  may  help  ameliorate  increases  in  disparities  and  possibly  reduce  existing  health  disparities  

�     

�  All  can  use  their  genome  in  their  care  

�  Information  on  affected  relatives  should  be  available  �  i.e.  no  more  hassles  about  convincing  payers  to  test  the  affected  individual  

first  

�  Simultaneous  research  of  clinical  sequencing  may  enable  scientists            to  rapidly  “catch  up,”  which  will  increase  genomic  findings  unique  to              certain  populations  

Enhancing  Newborn  Screening  �  State  newborn  screening  programs  have  minimized  health  disparities  for  

rare  genetic  conditions  through  universal  access  to  screening    

�  Involves  education,  screening,  diagnosis,  management,  follow-­‐up,  and  evaluation    

�  Genome  sequencing  is  feasible  for  clinical  use  in  the  newborn  period  

�  If  information  from  NGS  is  found  to  be  clinically  useful  in  newborns,  populations  that  cannot  access  it  will  be  at  a  significant  disadvantage    �  Instead,  access  will  be  determined  by  variables  already  known  to  contribute  

to  health  disparities,  such  as  consumer  demand,  health  insurance  status,  and  motivation  and  training  of  clinicians.    

�  If  sequence  information  will  only  have  marginal  clinical  benefit  for  years  to  come,  premature  implementation  of  sequencing  through  state  NBS  programs  may  divert  limited  resources  from  more  effective  public  health  programs.  

 Newborn  Screening  in  the  Genomic  Era:  Se�ng  a  Research  

� Workshop  held  December  2010  by  NIH,  DHHS,  and    Eunice  Kennedy  Shriver  National  Institute  of  Child  Health  and  Human  Development    

�  Purpose:  to  identify  elements  of  a  trans-­‐NIH  research  agenda  that  would  lead  to  the  application  of  new  genomics  concepts  and  technologies  to  newborn  screening  and  child  health  

Newborn  screening  vs.  Screening  of  Newborns    �  Newborn  Screening:  current  to  identify  actionable  childhood  diseases    

�  Screening  of  Newborns:  far  more  encompassing,  and  could  involve  using  sequencing  (or  other  technologies)  to  identify  adult-­‐onset  diseases  and/or  provide  other  information  that  would  benefit  patients  throughout  their  lives  �   lends  itself  well  to  answering  research  questions  –  both  about  specific  diseases  and  the  health  of  the  child  over  time  

�  Sequencing  could  insights  into  the  pathways  involved  in  the  particular  disease  that  may  not  be  well  understood  currently,  leading  to  novel  therapeutic  options      Ref:  Newborn  Screening  in  the  Genomic  Era:  Se�ng  a  Research  Report  

What  might  sequencing  in    newborn  screening  look  like?  �  Infrastructure  

�  Current  screening  takes  place  in  a  public  health  or  state-­‐run  environment    �  Evolve  to  a  collaborative  approach  between  health  care  institutions  and  

public  health  infrastructure  

�  Ideal  to  integrate  electronic  health  records  as  a  way  to  develop  their  use  in  research  and  clinical  decision-­‐making  

�  Where  would  sequencing  occur?  The  bedside?  

Ref:  Newborn  Screening  in  the  Genomic  Era:  Se�ng  a  Research  Report  

Infrastructure  (cont.)  �  Need  to  be  able  to  handle  the  rapid  increase  in  “positive”  reports  

�  Will  require  much  higher  accuracy  and  speed  than  is  current  &  much  lower  costs.    

�  Targeted  sequencing  (i.e.  sequencing  only  regions  that  can  be  interpreted)  may  be  a  viable  strategy  to  address  this  challenge  

Ref:  Newborn  Screening  in  the  Genomic  Era:  Se�ng  a  Research  Report  

What  might  sequencing  in  newborn  screening  look  like?  

� What  samples  to  test  and  when  to  test  them  �  Emphasis  on  Clinical  Validity  and  Clinical  Utility    �  Challenges  identified    

�  Which  conditions  to  focus  on  (treatable,  childhood,  etc.)  �  Which  variants  (genetic,  epigenetic,  proteomic)  to  screen  for  �  Breadth  of  genotyping  information  to  be  generated    �  Analysis  and  storage  in  the  medical  record    �  Insuring  access  to  the  underserved  

 

 Ref:  Newborn  Screening  in  the  Genomic  Era:  Se�ng  a  Research  Report  

What  might  sequencing  in  newborn  screening  look  like?  �  Ethical  Concerns  with  Parental  Permission  and  Education  

�  Segments  of  the  public  are  mistrustful  of  the  government  having  access  to  their  sequence  data    

�  “Opt  out”  for  current  screening  approach  �  “Opt  in”  for  genome  sequencing  �  “Opt  out”  or  “opt  in”  for  both?  

Poten�al  Challenges  to  Using  Sequencing  to  Benefit  Public  

Health  

Logis�cs:  Ordering  Sequencing  

� What  should  be  the  indication  for  testing?  �  Population  Screening  –  “Opportunistic  Screening”  

�  Deliberately  and  pre-­‐emptively  analyzing  the  genome  for  different  conditions  

�  Directed  Analysis  Approach  �  Target  only  relevant  variants,  which  will  require  new  bioinformatics  tools  and  robust  evidence  base  

�  Should  not  be  considered  incidental  findings  when  found  �  When  should  this  occur  in  the  lifespan?  

�  Newborn,  at  adulthood,  when  indication  presents  to  trigger…  

�  Risk  based  on  symptoms,  other  clinical  indication,  or  family  history  

�  Newborn  screening  

Logis�cs:  Ordering  Sequencing  

� Who  orders?    �  The  state,  primary  care,  specialists,  genetics  experts…  

� How  is  informed  consent  handled?  � Opt  in,  Opt  out,  None  �  Voluntary  vs.  mandatory  

Logis�cs:  Data  Management  �  Understanding  the  health  impact  of  sequencing  of  an  individual  presents  considerable  challenge  for  analysis,  interpretation  and  management  of  the  data  

�  Who  should  analyze?  �  What  and  where  are  data  stored?  

�  Data  is  huge!  �  Balance  between  accessibility  for  use  and  keeping  secure  �  Portability  –  how  can  useful  information  be  accessed  by  all  care  providers  presently  and  in  the  future  

�  Is  it  appropriate  re-­‐analyze  original  data  in  the  future  for  new  uses?    

Result  Disclosure:  Finding  the  Sweet  Spot  � What  to  give  back  and  when  is  a  topic  of  great  debate!  

�  Triggered  by  an  indication  (e.g.  symptoms,  family  history,  etc.)  �  Quality  of  the  finding  (i.e.  Clinical  validity/Clinical  utility)  �  What  about  results  with  reproductive  implications?  �  Age  (e.g.  child  vs.  adult;  post-­‐menopausal)    

�  Result  Disclosure  Models  �  Only  results  related  to  the  indication  (e.g.  symptoms,  fam  hx)  �  Any  result  that  is  clinically  valid  and  will  alter  health  care  management  �  List  will  vary  based  on  gender  and  age  (e.g.  if  post-­‐menopause  no  need  for  reproductive  information)  

                   

         

     

Privacy  and  Trust  

� Who  owns  and  can  access  the  data?  � How  can  this  be  regulated  effectively?  � What  access  will  law  enforcement  have  to  the  data?  � What  security  measures  are  necessary?  � Will  the  public  be  receptive?    Will  their  receptiveness  be  impacted  by  government  involvement?  

� How  do  the  aims  of  public  health  genomics  compare  to  eugenic  goals?  �  Eugenics  –  improve  quality  of  human  “stock”  �  Public  health  genomics  –  improve  health  via  intervention  

 Assessing  the  Economics  of  Genomic  Medicine:  IOM  Roundtable  Workshop  � Roundtable  on  Translating  Genomic-­‐Based  Research  for  Health  hosted  a  workshop  to  assess  economics  of  genomic  medicine  July  17–18,  2012  �  Brought  together  economists,  regulators,  payers,  biomedical  researchers,  patients,  providers,  and  other  stakeholders  

�  Improved  methods  are  needed  for  assessing  value,  personal  utility,  and  patient  preferences.    

Economic  Issues  �  The  US  does  not  have  universal  healthcare  

�  Access  to  new  technology  is  largely  driven  by  socioeconomic  factors  and  location  

�  Resources  available  for  public  health  initiatives  are  scarce  �  Many  caution  against  diverting  resources  from  other  effective,  less  costly  public  health  initiatives  

�  Costs  and  benefits  are  difficult  to  quantify  and  agree            on  for  the  various  stakeholders:    

�  public  health,  clinical  care,  and  academic  medicine  have  different  economic  assessment  models  

�  costs  and  benefits  can  be  measured  in  different  ways  �  i.e.  lives,  health  status,  money  

�  Improved  methods  are  needed  for  assessing  value,  personal  utility,  and  patient  preferences.    

Gene  Paten�ng  � May  impact  cost  and  hinder  methods  for  analysis  and  reporting  

 Affordable  Care  Act  �  Increase  the  number  who  have  health  insurance  coverage  �  expands  the  Medicaid  program  to  reach  more  low-­‐income  individuals  

�  offers  subsidies  to  middle-­‐class  individuals  who  need  help  to  afford  insurance  on  the  private  market  

�  creates  new  “health  insurance  exchanges”  �  no  lifetime  limits  on  coverage  �  cannot  deny  because  of  a  pre-­‐existing  condition  �  no  longer  able  to  charge  women  more  than  men    

 Affordable  Care  Act  �  Impact  on  genetic  screening  and  hereditary  cancer  �     

�  All  newborn  genetic  screening  tests  must  be  covered  without  a  co-­‐pay  (even  if  not  on  state  panel)  

�  Plans  required  to  cover  both  general  cancer  prevention  services  and  services  for  those  at  higher  risk  of  cancer  due  to  their  family  history  

�   plans  will  be  required  to  fully  cover  (no  copay)  mammography  and  colorectal  cancer  screenings  based  on  guidelines  

�  required  to  fully  cover  counseling  about  genetic  testing  for  BRCA  mutations  and  counseling  about  breast  cancer  chemoprevention  in  high  risk  individuals  

http://www.healthcare.gov/

Educa�on  � Physician    

� Despite  the  efforts  of  various  groups  and  public  health  initiatives  to  educate  physicians,  studies  still  indicate  severe  gaps  in  knowledge  and  competence  

� Desperate  need  for  decision  tools  and  just  in  time  resources  

� Public  � Numeracy  � Misconceptions  leading  to  fear  and  misuse  of  genomic  information  

� Distrust  of  the  Government  by  many  

Not  Enough  Gene�cs  Professionals  �  Limitations  in  Billing  and  Reimbursement  Hampers  Expansion  of  the  Genetic  Counseling  Profession  �  Licensure    

�  Licensure  is  tied  to  credentialing          and  billing  and  reimbursement  �  Also,  protects  the  public    

�  without  it,  anyone  can  claim  to          be  a  genetic  counselor  

� Need  to  be  recognized  as  providers  under  CMS  �  Necessary  to  bill  Medicaid  �  Takes  an  act  of  Congress  

� Number  of  Geneticists  Decreasing  

Health  Care  Infrastructure  � Health  systems  will  need  new  methods  and  a  stronger  infrastructure,  including  informatics,  to  track  and  analyze  the  downstream  consequences  of  providing  sequence  data  

…and  all  the  same  old  ethical  issues  � Discrimination  � Anxiety  � Duty  to  Re-­‐contact  � Non-­‐paternity  � Duty  to  Warn?  

NHGRI  to  Fund  into  Clinical  Genomics  Pilot  Projects  

� Up  to  four  grants  with  up  to  $750,000  in  Fiscal  Year  2014  and  up  to  $1  million  per  year  from  FY  2015  through  2017  

�  Funds  will  be  to  support  collaborative  genomic  medicine  pilot  demonstration  projects  that  will  test  the  feasibility  of,  and  develop  new  methods  for  incorporating  genomic  findings  into  patients’  care