Family History for Public Health and Preventive Medicine

transcript

Paula W. Yoon, ScD, MPH

Office of Genomics & Disease Prevention, CDC

'This is happening every day' (CNNSI Online-June 24, 2002)

• “Kile's father's death from cardiovascular disease in his 40s should have been a red flag signaling that the pitcher had an increased risk of the same fate”

• “Patients with a strong family history should get rigorous routine checkups including cholesterol screening, exercise stress tests or heart imaging tests”

Why focus on family history?

• news stories about sudden cardiac death

• FH is underutilized in preventive medicine

• geneticists use of pedigrees

• FH is risk factor for many common diseases

• current strategies not working (diet, exercise, smoking)

Jim Fixx 1932 - 1984

Risk factors for common disease

Obesity

Exercise

- only 25% of adults engage in recommended physical activity levels

Smoking

Public health impact of common disease Diabetes – 6th leading cause of death; prevalence 7.3% in 2000

Coronary Heart Disease – leading cause of death & disability; lifetime risk after age 40 is 49% males and 32% females

Stroke – 3rd leading cause of death; 600,000 new or recurrent strokes per year

Breast cancer – most common cancer diagnoses in women and 2nd cancer-related deaths; 203,500 new cases in 2002

Prostate cancer - most common cancer diagnosis in men and 2nd cancer-related deaths; 189,000 new cases in 2002

Colon cancer – 3rd most common cancer diagnosis and cancer-related death; 148,300 new cases in 2002

Family history is an independent risk factor for most chronic diseases of public health significance

What is family history?

reflects the consequences of genetic susceptibilities, shared environment, and

common behaviors

Family history is a risk factor for common diseases – AJPM Feb 2003• Population-based studies RR estimates –

CHD 2-5 type II diabetes 2-6asthma 2-4 breast cancer 2-6 colorectal cancer 2-5

• FHx explains a significant fraction of prevalent CHD – 14% Utah families had 72% early CHD and 48% all CHD

• 5-20% of people report a FHx of colorectal cancer

Could disease information about a person’s close relatives be used to predict their own risk for specific diseases?

Basic issues – validity and utility

Would individuals who may be at above average risk benefit from targeted interventions beyond what is recommended for the population at large ?

Family History Public Health Initiative

Evaluate the use of family history for assessing risk of common diseases and influencing early detection and prevention strategies• Phase 1 – Assessment of existing strategies and

development of criteria for FH tool

• Phase 2 – Tool development

• Phase 3 – Pilot testing and evaluation

• *Phase 4 - public health campaign and provider education programs

• literature review - evidence and identify data gaps

• Can family history be used as a tool for public health and preventive medicine? Genet in Med 2002; 4(4):304-310

• panel of experts – May 2002

• 10 articles in Am J Prev Med - Feb 2003

• family history work group

• development of research agenda and criteria for tools

Phase 1 - Assessment

8 criteria for inclusion of diseases

1. Public health burden2. Well defined case definition3. High awareness of disease status among relatives 4. Accurately reported by relatives5. Family history is a risk factor6. Population prevalence of family history as a risk factor 7. Effective interventions for primary and secondary prevention 8. Different recommendations for familial risk groups

• review of existing FH tools

• ongoing analysis of existing data sets – e.g, ARIC

• selection of diseases based on criteria

• development of FH tool and algorithms for risk categorization

• development of resource manual for primary care

Phase 2 – Tool development

Family History

Average

Moderate

Standard prevention recommendations

Personalized prevention recommendations

Referral for genetic evaluation and personalized prevention recommendations

Classification InterventionAssessment

Using family history for disease prevention

What makes a family history tool useful for public health and preventive medicine ?

• simple, easily applied, adaptable

• can identify people at high and moderate risk

• can be used in combination with other risk factors

• useful for targeting interventions

• positively influences healthy behaviors

Family History

18 diseases (year that defines early onset)- coronary heart disease (60)- sudden unexpected death (40)- stroke/TIA (mini stroke) (60)- hypertension (40)- diabetes (20)- blood clots in lungs or legs (40)- emphysema/lung disease (50)- kidney disease (50)- breast cancer (50)- ovarian cancer (50)- prostate cancer (50)- colon/colorectal cancer (50) - endometrial cancer (50)- thyroid cancer (50)- kidney cancer (50)

1st draft

Family History

Algorithms for classifying risk Family

HistoryTool

Scheuner M et al. Am J Med Genet 1997;71:315-324.

Resource manual for primary care

Family History

Binder with chapter for each disease

• recommended interventions for each level of risk

e.g., colorectal cancerAverage – screening at age 50Moderate – screening at age 40?High – referral for genetic consult

• explanation of potential Mendelian conditions underlying high risk

e.g., HNPCC, APC

• additional resources - web sites, brochures

Results of FHx screening for hypothetical, healthy 23-yr-old male

CVD 1 1st-degree relative moderate 60%diagn >60 yrs

Colorectal 2 1st-degree relatives high 50%Cancer 1 diag <50 yrs

Melanoma none average <1%

Condition Family History Risk Group LifetimeRisk

Settings and informatics

Electronic tool with applications • Personal computers• Internet• Hand-held devices

Potential settings• primary care providers• public health clinics• drug stores, schools• home

• develop pilot studies to fine tune the tool

• create funding opportunities

• evaluate the tool, algorithms and resource manual in different settings and populations

• evaluation framework - ACCE

Phase 3 – Pilot testing and Evaluation

ACCE Evaluation framework

Effective Intervention(Benefit)

NaturalHistory

EconomicEvaluation

QualityAssurance

Education Facilities

PilotTrials

Monitoring&

Evaluation

Ethical, Legal, &Social Implications

(safeguards& impediments)HealthRisks

ClinicalSpecificity

ClinicalSensitivity Prevalence

PPVNPV

Penetrance

Assay Robustness

QualityControl

AnalyticSpecificity

AnalyticSensitivity

Disorder&

Setting

Analytic validity – sensitivity, specificity

How well does the tool measure disease status among a person’s relatives?

Clinical validity – predictive value

How accurate is FH data for stratifying disease risk and predicting future disease?

ACCE Evaluation

NaturalHistory

EconomicEvaluation

QualityAssurance

PilotTrials

Monitoring&

Evaluation

ClinicalSpecificity

PPVNPV

Penetrance

Assay Robustness

QualityControl

AnalyticSpecificity

AnalyticSensitivity

Disorder&

Setting

Clinical utility – interventions, cost

What are the benefits and risks from both negative and positive family histories?

• Are there effective interventions available for primary and secondary prevention?

• Will targeted interventions based on FH have an impact on disease prevention?

• Is the approach cost-effective?

ACCE Evaluation

NaturalHistory

EconomicEvaluation

QualityAssurance

PilotTrials

Monitoring&

Evaluation

ClinicalSpecificity

PPVNPV

Penetrance

Assay Robustness

QualityControl

AnalyticSpecificity

AnalyticSensitivity

Disorder&

Setting

Ethical, Legal, and Social Implications

Are there issues affecting data collection and interpretation that might negatively impact individuals, families, and society ?

• Are there legal issues re informed consent, ownership of the data, or obligation to disclose?

• What is known about stigmatization, discrimination, privacy/confidentiality, and personal, family and social issues associated with family history assessment and risk labeling?

ACCE Evaluation

NaturalHistory

EconomicEvaluation

QualityAssurance

PilotTrials

Monitoring&

Evaluation

ClinicalSpecificity

PPVNPV

Penetrance

Assay Robustness

QualityControl

AnalyticSpecificity

AnalyticSensitivity

Disorder&

Setting

*Phase 4 – Public health campaign & provider education

• develop public health messages about the value of knowing your family history

• demo and disseminate the tools

• work with professional organizations to implement FH collection and use

• development and implement provider education

Why would this approach be of interest or value to providers?• evidence–based guidelines e.g., United States

Preventive Services Task Force (USPSTF)

• recommended by professional orgs (e.g., AAFP, ACPM)

• incentives – improving quality of care, CMEs, standardizing a complex process, making it faster and easier, simplify billing

• adaptable technology

Most common diseases result from interactions of multiple genes with multiple environmental factors in complex patterns that - despite progress in sequencing the human genome – are unlikley to be fully understood in the near future.

In the meantime, family medical history represents a “genomic tool” that can capture the interactions of genetic susceptibility, shared environment, and common behaviors in relation to disease risk.

Family history – a “genomic tool”

Family History Work Group

Paula Yoon, CDCMaren Scheuner, GenRiskKris Peterson, CDCChris Friedrich, Univ MSAnn Malarcher, CDC Daniela Seminara, NCIBarbara Bowman, CDCPaul Beatty, NCHSLadene Larsen, Dept Hlth UTDebra Irwin, UNCTemitope Keku, UNCKaren Edwards, Univ WAJean Jenkins, NHGRI

Teri Manolio, NHLBIScott Ramsey, Fred HutchinsonSharon Kardia, U MIIngrid Hall, CDCJean Jenkins, NHGRISteve Coughlin, CDCEugene Rich, Creighton U Theresa Finlayson, CDCTed Adams, Univ UTSaul Malozowski, NIDDKRobin Bennett, Univ WAEbony Bookman, NHLBIAnupam Tyagi

Family History for Public Health and Preventive Medicine

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