TECHNICAL BULLETIN Vol. 1 No. 2, January 2005

Understanding Flu Testing 1

2

3

4

Flu Facts

Choosing a Rapid Flu A+B Test

Better Patient Care

Better Financial Outcomes

7

BD Directigen™ Flu A+B Technology: Two-step lateral flow process enhanced by proprietary reagents

8

BD Directigen™ EZ Flu A+B Technology: Optimal readability

TECHNICAL BULLETIN

Flu Facts

2

l The flu is a contagious respiratory illness caused by Influenza viruses. Influenza A and B are the two types of Influenza viruses that cause epidemic human disease. Influenza C usually causes mild upper respiratory tract disease, and as such, is not as important clinically.

l Influenza A viruses are further categorized into subtypes on the basis of two surface antigens: hemagglutinin (H) and neuraminidase (N). For example, H3N2 is the strain that has caused recent Flu infections.

l In the U.S., more than 200,000 people are hospitalized each year from flu-related complications.1

l Approximately 36,000 people die from Flu every year.2 l Flu-related costs are estimated to be anywhere from $12-20 billion annually.3

l High-risk populations for serious Flu complications include: n older adults n young children n those with certain health conditions, including pregnancy l Diagnosis is most often determined clinically, based on symptoms during the appropriate time of year if disease is occurring in the community. Diagnostic tests are performed whenever diagnosis is uncertain and therapy is being considered. The FDA has cautioned healthcare professionals regarding the dangers of prescribing anti-viral drugs for Influenza based simply on clinical interpretation without a definitive flu diagnosis.4

1 2 3

4

As reported at the CDC website: http://www.cdc.gov/flu/about/qa/hospital.htm The CDC MMWR report P1, May 28, 2004/Vol. 53/HR-6 Flu season could cost $20B. (2004, October 14). Retrieved from CNN website: http://money.cnn.com/2004/10/18/news/economy/flu_costs/ As reported at the FDA website: http://www.fda.gov/bbs/topics/ANSWERS/ANS00995.html

VOL. 1 NO. 2, JANUARY 2005

3

Choosing a Rapid Flu A+B Test

There are currently several rapid Flu A+B tests available utilizing two major technologies, enzyme immunoassay (EIA) and chromatographic immunoassay (lateral flow). Each test offers a wide range of performance and specimen choices. Key factors that each laboratory should be aware of when choosing a rapid Flu A+B test include:

l l l l l l l

Test accuracy Capability to differentiate Flu A and Flu B Turnaround time Choices of specimen type Choices of transport medium Financial impact Reliable supply

BD Diagnostics provides two choices for rapid Flu A+B testing—BD Directigen Flu A+B and BD Directigen EZ Flu A+B.

BD Directigen Flu A+B Built on enzyme immunoassay technology.

BD Directigen EZ Flu A+B Built on lateral flow technology.

TECHNICAL BULLETIN

Choosing a Rapid Flu A+B Test

BD Directigen Flu A+B Technology

(continued)

BD Directigen EZ Flu A+B

Enzyme immunoassay (EIA)

Chromatographic immunoassay (lateral flow)

A purple triangle

A visable test line

Yes

Yes

Specimen Options

Nasal Washes Nasal Swabs Throat Swabs Nasalpharyngeal Washes Nasalpharyngeal Aspirates Bronchial-Alveolar Lavages

Lower Nasal Swabs Throat Swabs Nasalpharyngeal Washes Nasalpharyngeal Aspirates

Transport Options

20

20

Extraction Reagent

Improves antigen exposure

Improves antigen exposure and breaks down difficult mucoid specimens

Sufficient liquid controls provided

Sufficient liquid controls provided

Time to Results

15 minutes

15 minutes

Number of Steps

Multiple steps

Two steps

Kit Configuration

20 Tests

30 Tests

Cat. No.

256010

256050

Positive Result Indicator Differentiation of Flu A+B

External Controls

VOL. 1 NO. 2, JANUARY 2005

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5

Better Patient Care

Rapid identification of Influenza cases is essential, both for the initiation of antiviral therapy when appropriate, and also for the avoidance of improper use of antibiotics. Confirmatory diagnosis of Influenza is also important to aid in preventing transmission of Influenza to high-risk patients. The use of a rapid test kit with increased sensitivity will result in more accurate patient diagnosis. Improper diagnosis of influenza can lead to inappropriate use of antibiotics, lack of appropriate antiviral therapy and increased spread of influenza to high-risk patients and others in the community. In addition to being the first Flu kit on the market, the high accuracy of the BD Directigen Flu A+B kit has made it the #1 rapid Flu A+B test used by hospital labs. As the innovator of lateral flow technology, BD is pleased to take Flu testing to a new level of performance with the lateral flowbased BD Directigen EZ Flu A+B Test. BD Directigen EZ Flu A+B Clinical Trial Performance Compared to Culture hnology

NP Washes / Aspirates BD EZ Flu A+B

1

Cell Culture _ +

Flu A

+ _

67

0

5

196

Flu B

+ _

12

1

0

255

Throat / Lower Nasal Swabs

Sensitivity

Specificity

BD EZ Flu A+B

93.1%

100.0%

+ _

100.0%

99.6%

+ _

Cell Culture _ + 5

4

1

91

0

0

0

101

101 patient throat or lower nasal swab samples were tested during our clinical trial. However, due to the ~99% prevalence of Flu A during the 2003-2004 Flu season*, none of them were confirmed positive for Flu B. The excellent performance for both Flu A and Flu B demonstrated with NP washes and aspirates suggests that it will perform similarly with lower nasal swabs and throat swabs. Results with Flu A on swabs were also very good. As a result, similar results are expected for Flu B swab specimens. Additionally, an in-house study comparing the BD Directigen Flu A+B test to the BD Directigen EZ Flu A+B test was conducted with seeded LN/T swabs. No significant difference between the two tests was observed, as they had an overall agreement of 98% (118/121)**.

** As reported by the CDC at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5313a2.htm. ** Data on file.

TECHNICAL BULLETIN

Sensitivity

Specificity

83.3%

95.8%

N/A1

100.0%

Better Financial Outcomes

6

The choice of Flu A+B kit impacts both the cost of patient therapy and the level of reimbursement for laboratories. I. Financial Impact to Reimbursement Correct coding and subsequent reimbursement for any laboratory procedure, including Influenza tests can be a challenging process. Factors to be aware of when choosing a CPT code for Influenza testing include: 1. CLIA Waived vs. Moderately Complex Tests 2. Non-differentiated vs. Differentiated Tests l Tests that identify Influenza, but which cannot differentiate Flu A and Flu B can be reimbursed only once.

l Tests that differentiate Flu A and Flu B may be billed twice, only if separate test procedures are conducted with separate test results.

For differentiated tests: 3. Single Step vs. Multiple Step Tests l For tests with a single step, the CPT code 87450 should be used. For example: CPT code 87450 should be billed once when using Nasal Wash/Aspirate specimens with the Binax NOW Flu kits.

l Multiple step CPT code 87400 applies to tests requiring multiple steps. 4. Single Test vs. Multiple Test Procedures

l If a single test procedure is used to differentiate between Flu A and Flu B, then the appropriate CPT code may be billed once. continued on page 7

VOL. 1 NO. 2, JANUARY 2005

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Better Financial Outcomes (continued)

For example: The Remel Xpect Flu A&B, Binax NOW Flu A&B, Wampole ClearView Flu A+B and Quidel QuickView Flu A+B tests require one sample addition, and so involve only one procedure. It is not appropriate to bill twice for these single test procedures.

l If separate multi-step procedures are conducted to separately identify both Flu A and Flu B, then the appropriate CPT code can be billed twice. For example: BD Directigen Flu A+B and BD Directigen EZ Flu A+B tests require separate procedures with differentiated results for Flu A and Flu B and so can be billed twice for 87400.

TECHNICAL BULLETIN

Better Financial Outcomes (continued)

II. Financial Impact to Your Laboratory A lot of time and many resource hours can be spent on validating specific transport media and specimen type requirements. Choosing a differentiated Flu A+B test with maximum flexibility in these areas can result in considerable savings in time and money for your laboratory. III. Financial Impact to Patient Therapy Increasingly, more adults are being treated for the flu due to an increased availability of antiviral drugs. Common antiviral drugs for Influenza fall into one of two categories, those that are Influenza A specific, and those that treat both Influenza A and B. The combined Influenza A+B drugs (Zanamivir and Oseltamivir) are significantly more expensive than those that are Influenza A specific (Amantadine and Rimantadine). The use of a differentiated Flu test, which provides separate results for both Flu A and Flu B, enables the use of targeted antiviral therapies that treat specifically for either Flu A or Flu B. When using Influenza Treatment Costs other Flu tests that do not differentiate between Flu A and Flu B, treatment must Cost of Rx Course of Treatment Drug Cost of Rx rely on more expensive broad-spectrum antiviral drugs. Influenza A Specific Drugs 6

5

Amantadine

7 days - 2x per day

$12.00

$18.99 7

Rimantadine

7 days - 2x per day

$34.00

$33.45

Combined Influenza A+B Drugs Zanamivir

5 days - 2x per day

$50.00

$54.41

Oseltamivir

5 days - 2x per day

$65.00

$65.99

1 2 3

Improper diagnosis of Influenza can also result both in improper therapy as well as continued spread of the disease to highrisk patients and others in the community.

Costs are from Independent Pharmacy. Costs are from the RiteAid website: http://www.riteaid.com/ Cost is for a 60-tab packet.

VOL. 1 NO. 2, JANUARY 2005

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9

BD Directigen™ EZ Flu A+B Technology: Two-step lateral flow process enhanced by proprietary reagents The BD Directigen EZ Flu A+B test utilizes a unique, patented form of lateral flow technology invented by BD. This technology enables a simpler workflow while providing maximum performance and easy readability. In order to detect all strains of Influenza subtypes, rapid Flu tests are typically designed to detect the Influenza nucleoprotein. The nucleoprotein resides within the virus and is well conserved among subtypes. As a result, viral extraction is necessary to release the nucleoprotein and maximize detection. The BD Directigen EZ Flu A+B test utilizes a proprietary sample processing reagent specially developed to break down mucoid specimens for maximal antigen release (compare illustrations 1 and 2). Increased antigen release can allow for improved sensitivity.

Illustration 1 Influenza antigen release without sample processing.

Other lateral flow Flu A+B tests may lack the sample process step or may require that mucoid samples be sonicated prior to testing.

Illustration 2 Influenza antigen release after sample processing.

TECHNICAL BULLETIN

BD Directigen™ EZ Flu A+B Technology: Optimal readability The BD Directigen EZ Flu A+B test is designed for easy readability. Variations in test line intensity are typically seen with chromoatographic (lateral flow) immunoassays. The sample process reagent in the BD Directigen EZ Fly A+B test helps create a clear white background in the test result window. This allows for easier to read test lines. Optimized concentrations of antibodies and detector provide clearer test lines that are easier to read even with weak positive samples. BD Directigen EZ Flu A+B kit features:

l Unmatched accuracy to ensure proper diagnosis l Two separate tests to differentiate Flu A and Flu B using one device

l Easy-to-use workflow l Multiple specimen types and transport choices for maximum flexibility

l Clear white background in test result window for improved readability

l Clear test line intensity even with weak positive samples l Procedural controls built into each test strip to ensure test integrity

l Liquid controls included to allow for easy QC compliance l Room temperature storage

VOL. 1 NO. 2, JANUARY 2005

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Featured in this bulletin: Cat. No.

Unit

Description

256050

30 tests

BD Directigen™ EZ Flu A+B Kit

256010

20 tests

BD Directigen™ Flu A+B Kit

Other BD Directigen™ EZ Respiratory Testing Products: Cat. No.

Unit

Description

256030

30 tests

BD Directigen™ EZ RSV Kit

253020

20 tests

BD Directigen™ RSV Kit

253040

40 tests

BD Directigen™ RSV Kit

256017

30 tests

BD Directigen™ EZ Group A Strep Kit

BD Diagnostics 7 Loveton Circle Sparks, MD 21152-0999 USA 800.638.8663 www.bd.com/ds

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Expect is a trademark of Remel Inc. Quidel and QuickVue are registered trademarks of Quidel Corporation. NOW is a registered trademark of Binax, Inc. BD, BD Logo and Directigen are trademarks of Becton, Dickinson and Company. ©2004 BD. 0-2740 January 2005

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