What is the Cardiovascular Biomarker Standardization Program?

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• What is the Cardiovascular Biomarker
  Standardization Program?

Walter Snip Young, PhD Consultant,
NACDD Hubert Vesper, PhD Chief, CDC Clinical
Chemistry Branch
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What is standardization?

• When we buy fruit at a market we expect the
  scales to be accurate.
• When we pump gas we expect to get the amount of
  gas the display shows us.
• Scales and gas pumps are checked for accuracy and
  certified with a sticker.
• It seems reasonable that we assume that accuracy
  of blood measurements is checked the same way.
• This is NOT the case.

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Problem

• Variability in clinical test results exists
• - across laboratories
• - across lab equipment manufacturers
• - by varied lab procedures and
• - over time.
• Variability contributes to preventable morbidity
  mortality from chronic diseases

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Quick Poll

• Have you ever asked your provider about the
  accuracy and reliability of your cholesterol
  tests?

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Solution

• CDC Clinical Chemistry Lab assigns reference
  values to serum samples, the same way reference
  balances are used to create a certified weight.
• The Cardiovascular Standardization Program sends
  these serum samples to laboratories and equipment
  manufacturers for certification.

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Why is NACDD involved?

• Rationale Activity Domains
• Domain Health system interventions to improve
  the effective delivery and use of clinical and
  other preventive services
• Domain Strategies to improve community-clinical
  linkages ensuring that communities support and
  clinics refer patients to programs services for
  management of chronic conditions

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Deaths Prevented or Postponed and Life-Years
Gained Attributable to the LSP and CRMLN, 2000
Attributable to LSP and CRMLN Deaths Prevented or Postponed Life-Years Gained
0.5 558 6,756
1 1,116 13,512
5 5,579 67,561
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FY08 Monitary Benefits of the Lipid
Standardization Program
Percentage Attributable to the LSP and CRMLN Life-Years (LYs) Gained Benefits ( millions) Benefits ( millions) Benefits ( millions)
Percentage Attributable to the LSP and CRMLN Life-Years (LYs) Gained 50,000 /LY 113,000/LY 300,000/LY
0.5 6,756 338 763 2,027
1 13,512 676 1,527 4,054
5 67,561 3,378 7,634 20,268
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Importance of Accuracy in Blood Lipid Testing

• Public health surveillance and evaluation
• - Tracking population trends
• - Program evaluation (cholesterol screening /
  education)
• Research testing
• - Early cholesterol research was limited due to
  high variability in lipid testing accuracy.
• - Standardization allows results from disparate
  studies to be compared across labs, procedures
  and over different time periods.
• Clinical testing
• - Increased accuracy reduces misclassification,
  missed diagnoses
• - Without standardization More false
  positives, false negatives, needless treatment
  costs , preventable human costs of no
  treatment.

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What cardiovascular tests are currently
standardized?

• Only lipid testing. (Lipid Std. Program)
• Cardiovascular laboratory tests such as
  troponin I-used as a test of several different
  heart disorders, including heart attack.
• B-naturetic peptide - used to treat
  decompensated heart failure
• C-reactive protein - used mainly as a marker of
  inflammation determining disease progress or
  treatment effectiveness
• are NOT standardized.

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Quick Poll

• Do you think the results of your lab tests for
  cholesterol might be dependent on the lab your
  provider uses?

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Clinical Chemistry Branch Div. of Lab. Sciences,
Center for Environmental Health

• Goal Improve the diagnosis, treatment and
  prevention of cardiovascular diseases through
  standardized laboratory testing.
• Service Objectives
• Support national international clinical
  laboratory communities that want the highest
  reliability of their tests.
• Provide assistance and advice on lipid testing,
• Help assure the quality of lipid testing in
  studies.

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NACDD Partnership Roles with Division of
Laboratory Sciences

• Chair manage the Cardiovascular Biomarker
  Standardization Steering Committee (CBSSC)
• Educate public, public health community
  policymakers re
• A) relationship of standardization to clinical
  outcomes
• B) nutrition status in the U.S. population.
• 3. Advocate for standardization of chronic
  disease tests.
• 4. Produce data to support educational activities
  
• (e.g., A cost-benefit analysis of lipid
  standardization in U.S.)
• Hoerger TJ, Wittenborn JS, Young W. A
  cost-benefit analysis of lipid standardization in
  the United States. Prev Chronic Dis
  20118(6)XX. http//www.cdc.gov/pcd/issues/2011/n
  ov/10_0253.htm..

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NACCD brochure about clinical laboratory
standardization

• Goal
• Provide basic information about
• Standardization,
• Standardization process,
• Benefits of Standardization
• Target Audience
• Public health officials
• Physicians
• Patient care and advocacy groups
• Those who benefit from standardization
• The brochure uses examples from the CDC Lipid
  Standardization Program

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Roles / Activities of CBSSC?

• Provides expert opinion on
• - Expansion of CVD test standardization, beyond
  the Lipid Standardization Program
• - Reviews new CDC technologies research
• - Addition of mass spectrometry methods
• - Progress on new method for measuring small
  particle LDL
• - Suggests funding sources advocates for
• expansion of CV standardization program

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Cardiovascular Biomarker Standardization Steering
Committee (CBSSC) Members

• Neil Greenberg, PhD, Former Director, Regulatory
  Affairs, Clinical Lab Products,lOrtho Clinical
  Diagnostics
• Elena Kuklina, MD, PhD, Sr. Service Fellow, Div
  of Heart Disease and Stroke Prevention, CDC
• Elizabeth Teng Leary, PhD, Chief Scientific
  Officer, Pacific Biometrics.
• Nader Rifai, PhD, Director, Clinical Chemistry,
  Laboratory Medicine, Boston Childrens Hospital
• Russell Tracy, PhD, Sr. Assoc. Dean for Research
  and Academic Affairs, University of Vermont,
  College of Medicine,
• Donald A. Wiebe, PhD, Assoc Prof, School of
  Medicine and Public Health Pathology and
  Laboratory Medicine, U of Wisconsin
• Peter W. F. Wilson, MD, Emory U., School of
  Medicine, Department of Medicine, Cardiology
  Division

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What are the steps to the Lipid Standardization
Process?.

• Step 1 Reference System - A reference system
  consisting of reference methods and materials is
  established.
• Step 2 Calibration - Clinical tests are
  calibrated using the single donor sera developed
  in the first step.
• Step 3 Patient Testing Assessment - Patient
  testing is assessed to monitor accuracy and
  precision.

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Benefits to Public health officials

• Public health officials can reliably evaluate
  public health efforts by monitoring biomarkers in
  populations over many years even when tests and
  testing equipment change over time.

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Benefits to Physicians

• Physicians can diagnose treat patients more
  effectively with accurate tests that allow the
  use of evidence-based clinical guidelines.

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Benefits to Researchers

• Researchers can compile compare cardiovascular
  testing data across laboratories and studies to
  formulate evidence-based patient guidelines
  public health policies.

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Benefits to Patients

• Patients can be assured of the accuracy of their
  clinical tests, more confident in disease
  prevention and treatment recommendations, and
  perhaps motivated to be more compliant with
  clinical recommendations.

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Conclusion Cardiovascular Biomarker
Standardization Program assures accuracy and
reliability of tests for

• Total cholesterol (TC)
• High-density lipoprotein
• cholesterol (HDL-C)
• Low-density lipoprotein
• cholesterol (LDL-C)

• Triglycerides (TG)
• Apolipoprotien B
• C-reactive protein
• LDL-subfractions
• in development

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Conclusion Standardized laboratory tests are
needed to

• Accurately diagnose patients provide better
  patient care
• Reliably monitor population health and assess
  effectiveness of public health activities
• Inform decision-making within clinical and
  public health domains

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For Additional Information

• NACDD Walter Snip Young, PhD
• ? [phone] ? www.chronicdisease.org ?
  young_at_chronicdisease.org
• CDC, Clin. Chem. Branch- Hubert Vesper, PhD
• ? [phone]
• ? hvesper_at_cdc.gov

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