What is the Cardiovascular Biomarker Standardization

Program?

Walter ‘Snip’ Young, PhD

Consultant, NACDD

Hubert Vesper, PhD

Chief, CDC Clinical Chemistry Branch

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.

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

Quick Poll

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

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.

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

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

FY08 Monitary Benefits of the Lipid Standardization Program

Percentage Attributable to the LSP and CRMLN

Life-Years (LYs)

Gained

Benefits ($ millions)

$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

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.

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.

Quick Poll

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

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.

CDC User

Suggest to change "CRMLN/Accurcay-based PT" to "Clinical Lab Standardization" or "Patient Care Testing Standardization"to emphasize that we do adress testing done in patient care.

NACDD Partnership Roles with Division of Laboratory Sciences

1. Chair & manage the Cardiovascular Biomarker Standardization Steering Committee (CBSSC)

2. 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 2011;8(6):XX. http://www.cdc.gov/pcd/issues/2011/nov/10_0253.htm..

NACCD brochure about clinical laboratory standardization

GoalProvide 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

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

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 Children’s 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

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.

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.

Benefits to: Physicians

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

Benefits to: Researchers

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

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.

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

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

For Additional InformationNACDD – Walter ‘Snip’ Young, PhD

(303) 358-4681 www.chronicdisease.org young@chronicdisease.org

CDC, Clin. Chem. Branch- Hubert Vesper, PhD

(770) 488-4191 hvesper@cdc.gov

Improve Educate Prevent Promote