implica ons of genome sequencing on public health ...diagnosis, management, follow- ‐up, and...
TRANSCRIPT
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
Ss
Tackling Complex Disease with Public Health Ini�a�ves
Is sequencing the answer?
Dreambuildercoachingprogram.com
Ss
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