Transcript How Do We Individualize Guidelines in an Era of Personalized

How Do We Individualize Guidelines in an Era of
Personalized Medicine?
Credit: The White House
Douglas K. Owens, MD, MS
VA Palo Alto Health Care System
Stanford University, Stanford CA, USA
September 2016
Disclosures and Disclaimer
• No financial disclosures
• Chair, American College of Physicians Guideline
Group
• Member, U.S. Preventive Service Task Force
2012-2015
• Disclaimer: Views mine, not USPSTF or US
Government
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Individualizing Guidelines
Things we know about someone
Age
Comorbidities
Gender
Preferences
Genomic data
Change Risk
Modify
disease course
Modify
response to
intervention
Evidence
Health Outcomes
(length and quality of
life)
Intervention
Lung cancer: National Lung Screening Trial
Statins: Primary prevention trials
Intervention
Intermediate
Outcomes
HIV screening
Health Outcomes
(length and quality of
life)
Goal: Determine Net Benefit
Age
Comorbidities
Gender
Preferences
Genomic data
Benefit
Harms
Examples from the U.S. Preventive Services
Task Force
• Aspirin for prevention of CVD and colorectal
cancer
• Statins for CVD prevention
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USPSTF Members
• The 16 volunteer members represent disciplines of primary care
including family medicine, internal medicine, nursing, obstetrics
and gynecology, pediatrics, and behavioral medicine
• Led by a Chair and Vice Chairs
• Serve 4-year terms
• Appointed by AHRQ Director with guidance from Chair and
Vice Chairs
• Current members include deans, medical directors, chief health
officers, practicing clinicians, and professors
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The USPSTF
• Makes recommendations on clinical preventive services to
primary care clinicians
– screening tests
– counseling
– preventive medications
• Affordable Care Act requires insurers to cover without co-pay
any services rated as A or B (recommended) by USPSTF
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Evidence review supports effectiveness and
harms of aspirin
• 22% reduction in non-fatal myocardial infarction
• 14% reduction in non-fatal stroke
• 33% reduction in mortality of colorectal cancer at
20 years
• 58% increase in gastrointestinal bleeding
• 27% increase in intracranial bleeding
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Goal: Determine Net Benefit of Aspirin
Age
Comorbidities
Gender
Preferences
Genomic data
Benefit
nonfatal
MI, stroke,
CRC
Harms
GI,
intracranial
bleeds
Balance of benefit and harms depends on
absolute risks (not relative risks)
• Greater absolute risk of CVD means greater benefit
from aspirin
• Risk of CVD depends on age, gender, and
comorbidities
• USPSTF recommended use of the ACC/AHA
pooled risk equation to estimate CVD risk
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ACC/AHA pooled risk equation for predicting 10-year CVD risk
No similar risk estimator for bleeding risk
• Risk of bleeding depends on:
» Aspirin dose and duration
» History of GI ulcers or abdominal pain
» Renal failure, severe liver disease, thrombocytopenia,
bleeding disorders, diabetes
» Other medications, including NSAIDs and
anticoagulants
» Male sex, OLDER AGE, current smoker, uncontrolled
hypertension
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Goal: Determine Net Benefit of Aspirin
Age
Comorbidities
Gender
Preferences
Genomic data
Benefit
nonfatal
MI, stroke,
CRC
Harms
GI,
intracranial
bleeds
How did we balance these complex benefits
and harms and allow for individualization?
• Decision model to estimate:
»
»
»
»
»
Benefits: MI, stroke, cancer averted
Harms: GI bleeds, intracranial bleeds
Life years gained (or lost)
Quality-adjusted life years gained (or lost)
Effect of patient preferences (that is, judgements about
quality of life with health outcomes and medication)
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Estimated health outcomes from use of aspirin
Bibbins-Domingo et al, USPSTF. Ann Intern Med 2016: 164(12):836-45
Goal: Determine Net Benefit of Aspirin
Age
Comorbidities
Gender
Preferences
Genomic data
Benefit
nonfatal
MI, stroke,
CRC
Harms
GI,
intracranial
bleeds
USPSTF Recommendation – initiate aspirin if:
• 50 to 59
»
»
»
»
> 10% 10 year CV risk
NO increased bleeding risk
life expectancy of at least 10 years
willing to take aspirin for 10 years (grade = B)
• 60 to 69
» same criteria
» and patient places higher value on potential benefits
than harms (grade = C)
Bibbins-Domingo et al, USPSTF. Ann Intern Med 2016: 164(12):836-45
USPSTF (draft) recommends statin if:
• 40 to 75 years
» > 10% 10-year CVD risk AND
» One or more of the following risk factors:
– Hypertension
– Dyslipidemia
– Diabetes
– Smoking
– B recommendation
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Data is not always available to individualize
• Black women have higher death rate from breast
cancer
(USPSTF Screening for breast cancer. Ann Intern Med 2016 164: 279-296.)
• Black race is associated with higher incidence and
mortality from colorectal cancer
(USPSTF CRC screening JAMA.
2016;315(23):2564-2575)
• Black men have increased risk of developing and
dying of prostate cancer
(USPSTF Prostate cancer screening. Ann Intern Med. 2012;157:120-
134)
• Aspirin use in people over 75
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How to individualize guidelines in an era of
personalized/precision medicine?
Credit: www.whitehouse.gov
Conclusion: Feasible to individualize guidelines
• Requires evidence linking personal characteristics to
» Risk
» Disease course
» Different treatment response
• Decide what standard of evidence is required
» How much extrapolation is reasonable?
• Modeling can be very useful, may be essential
» But is limited by data also
» Is modeling sufficient?
Thanks