Transcript Integrating Genomics into Clinical Practice Jan Dorman, PhD University of Pittsburgh School of Nursing [email protected].

Integrating Genomics into
Clinical Practice
Jan Dorman, PhD
University of Pittsburgh
School of Nursing
[email protected]
Applications of Genomics to
Clinical Practice

Molecular diagnosis
– $1000 for human genome sequence

Prediction of a healthy person’s risk of disease
– Including cancer, cardiovascular disease, diabetes, etc.

Evaluation of responses to drugs and
environmental agents
– Pharmacogenomics
Where do clinicians begin?
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Begin with assessment of family history
“Even when an individual’s genome can be
displayed on a personal microchip, interpreting
that information will depend in large part, on
the biological and environmental contexts in
which the genome is expressed, and the family
milieu is as good a guide as any.”
Pyeritz RE. JAMA 278:235. 1997
Family Health History

Is an important risk factor for chronic
diseases that reflects
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Inherited genetic susceptibility
Shared environment risk factors (diet)
Cultural factors (religious practices)
Common behaviors (smoking, physical activity)
Prior to offering any genetic susceptibility
testing, a clinician needs to assess the
family history of disease
– Who should be tested?
– What genes should be tested?
Family History of Diabetes

T2D is an independent risk factor for the disease
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88-95% have affected 1st degree relatives
– 70-77% have affected 2nd degree relative
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Individuals with a positive family history are about
2-6 times more likely to develop T2D than those
with a negative family history
– Risk ~40% if 1 T2D parent; ~80% if 2 T2D parents
Family History of Diabetes

FH identifies a group of high risk individuals
– Using a simple and inexpensive approach
– Who may benefit from early detection
– To develop personal and family-based risk factor
modification strategies
– In the future, may benefit from genetic testing
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Has been difficult to find genes for T2D
– Late age at onset
– Polygenic inheritance
• Multiple genes with small effects
– Multifactorial inheritance
Collecting Family History
Information in Clinical Practice

Barriers
– Underestimation (by clinicians and
patients) of value of family history
information
– Limited knowledge and training in human
genetics
• National Coalition for Health Professional
Education in Genetics (NCHPEG) endorsed
core competencies for all health-care
professionals in 2000
NCHPEG Core Competencies
Represents minimum knowledge, skills and
attitudes necessary for health
professionals in all disciplines to provide
patient care that involves awareness of
genetic issues and concerns
– Medicine
– Nursing
– Public Health
- Dentistry
- Psychology
- Social work
NCHPEG Core Competencies

Appreciate limitations of his or her genetic
expertise
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Understand the social and psychological
implications of genetics
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Know how and when to make a referral to a genetic
professional
Some NCHPEG
Recommendations
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Knowledge
– Importance of family history (minimum of 3
generations) in assessing predisposition to
disease
– The range of genetic approaches to treatment
of disease
– Resources available to assist clients seeking
genetic information
– The indications for genetic testing and / or
gene-based interventions
Some NCHPEG
Recommendations
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Skills
– Gather genetic FH information, including multiple
generation pedigrees
– Identify families who would benefit from genetic
services
• Educate individuals regarding these services, and their risks
and benefits
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Attitudes
– Appreciate the sensitivity of genetic information and the
need for privacy and confidentiality
– Demonstrate willingness to update genetics knowledge at
frequent intervals
Collecting Family History
Information in Clinical Practice

Other barriers
– Lack of time
– Lack of reimbursement for collecting
the information
– Concerns about insurance / employment
discrimination
– Lack of convenient tools / software for
data collection
Family
History
Tools
in the
Popular
Literature
US Surgeon General’s Family
History Initiative
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First National Family History Day, Thanksgiving,
11/25/2004
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US Partners
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Developed tool “My Family Health Portrait”
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Office of the Surgeon General
National Human Genome Research Institute (NHGRI)
Centers for Disease Control and Prevention (CDC)
Agency for Healthcare Research and Quality (AHRQ)
Health Resources and Services Administration (HRSA)
– Download free at http://www.hhs.gov/familyhistory
– Focuses on chronic diseases
US Surgeon General’s Family
History Initiative
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Increase awareness among the public and health
professionals of the value of family history for
disease prevention and health promotion
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Provide
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Increase genomics and health literacy
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Prepare the public and health professionals for
the coming era of genomic medicine
– Tools to gather information, assess risk, and guide
prevention strategies
– Educational materials to facilitate communication about
familial risk between patients and providers
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Criteria for Diseases Included
in “My Family Health Portrait”
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Substantial public health burden
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Clear case definition
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High awareness of disease status among relatives
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Family history is an established risk factor
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Effective interventions for primary and secondary
prevention
– Accurate reporting by family members
“My Family Health Portrait”
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Diseases included
– Stroke
– Type 2 diabetes
– Cancer
• Breast
• Colorectal
• Ovarian
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Information may be taken electronically or
using paper and pencil instruments
“My Family Health Portrait”
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Information collected
– Age, gender, race / ethnicity
– Number of relatives in each category (mother,
father, children, etc.)
• Specific for 1st and 2nd degree relatives
– History of 6 diseases, age at diagnosis
– Questions about results of screening tests,
frequency / reasons for clinician visits
– Risk factors (e.g., BMI, smoking, diet, exercise,
etc.)
http://www.hhs.gov/familyhistory/
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“Family Healthware”
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Family risk level is based on
– Number of affected family members, degree of
relatedness, number of generations affected
– Mendelian modes of inheritance
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Risk levels
– Strong
• Affected 1st degree relative with early-onset disease
• Multiple affected relatives
• Hereditary syndrome suspected
– Moderate
• Affected 1st degree relative with late-onset disease
• Two affected 2nd degree relatives
– Average
• No 1st degree or one 2nd degree relative affected
Familial Risk Classification
Average
Family
Health
Portrait
Moderate
Strong
Standard Public
Health Prevention
Recommendations
Personalized
Prevention
Recommendations
Personalized Prevention
Recommendations
and Referral
“Family Healthware”
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Prevention messages are based
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Familial risk level
Answers to question about screening tests
Health behaviors
Age
Gender
Evidence-based prevention approaches
Prevention Strategies for High
Risk Families
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Targeted lifestyle changes such as diet, exercise
and stopping smoking
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Screening at earlier ages, more frequently and
with more intensive methods than might be used
of average risk individuals
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Use of chemoprevention approaches
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Referral to a generalist or specialist
– Aspirin
Prevention Strategies for High
Risk Families

Will identification of high risk families lead to
behavior change?
– Positive and negative studies
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Consider the tool used for data collection
– Interactive vs. web-based tools
• Complete at home, with input from family
members
• In clinician’s office
– Personal digital assistants (PDAs)
• With evidence-based guidelines, monitoring
and feedback options
Evaluation of Family History
Tools
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Before family history is accepted as a screening
tool, must evaluate
– Accuracy and reliability
– Effectiveness of risk stratification on early detection
and prevention
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4 components of evaluation
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Same issues would need to be addressed before
genetic testing could be used as a screening tool
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Analytical validity
Clinical validity
Clinical utility
Ethical, legal and social issues
Evaluation Framework
Effective
Intervention
(Benefit)
Natural
History
Quality
Assurance
Clinical
Sensitivity Prevalence
Clinical
Specificity
Ethical, Legal, &
Social Implications
(safeguards& impediments)
Pilot
Trials
PPV
NPV
Disorder
&
Setting
Penetrance
Analytic
Assay
Sensitivity
Robustness
Analytic Quality
Specificity Control
Monitoring
&
Evaluation
Education
Facilities
Health
Risks
Economic
Evaluation