LYMEPOLICYWONK: The CDC, the FDA and Lyme Disease Lab Tests: Two-Tiered Tests, IGeneX, the C6, and the New Culture Test
16th March 2013
The CDC website now states that before the CDC will recommend new tests, “their performance must be demonstrated to be equal to or better than the results of the existing procedure, and they must be FDA approved.” But is FDA approval required for diagnostic tests? No, FDA approval is only required for tests that are marketed to other labs. Single lab tests, like those offered by IGeneX and Advanced Laboratory Services (ALS) do not require FDA approval. Instead, federal law requires that they undergo a rigorous validation process established by the Centers for Medicare and Medicaid Services (CMS) and Clinical Laboratory Improvement Amendments (CLIA). CMS and CLIA require developers to prove that their tests are accurate, precise, sensitive, and specific prior to marketing. Both IGeneX and ALS diagnostic tests are CLIA and CMS approved.
To pass CLIA, Lyme tests must demonstrate that they accurately detect positive samples of blood and test negative on control samples of blood. This is how these tests are validated. These samples are provided by the CDC—so there is no dispute that the samples are accurate. Why is the CDC asking for more than compliance with federal regulations using CDC sample sets?
And, what about its other requirement—that the test must be equal to or better than the existing two-tiered testing procedure recommended by the CDC. Research shows that the current two-tiered testing procedures do more harm than good. While the testing has few false positives (called “high specificity”), it has many false negatives (or “low sensitivity”). Two-tiered testing misses 44 of every 100 patients who have Lyme disease. Imagine if that were the case with AIDS! Take a look at the table below from the article “Let’s Tackle the Testing”:
What plan do the CDC and NIH have for the future of testing? Well, the NIH has invested heavily in the C6 test. The C6 is commercially marketed by two companies, Immunetics and DiaSorin, both of whom have commercial ties with Dr. Wormser, who authored the IDSA guidelines which require positive lab tests for diagnosis. In addition, Immunetics receives NIH research grants, which fund Dr. Wormser’s research. Dr. Barbara Johnson of the CDC and Dr. Gary Wormser, who authored the IDSA guidelines, have jointly published a number of articles supporting this test, which is FDA approved, but performs no better than the two-tiered strategy. So, why is the American public funding C6 research?
What plan do the CDC and NIH have for the future of testing? Well, the NIH has invested heavily in the C6 test. The C6 is commercially marketed by two companies, Immunetics and DiaSorin, both of whom have commercial ties with Dr. Wormser, who authored the IDSA guidelines which require positive lab tests for diagnosis. In addition, Immunetics receives NIH research grants, which fund Dr. Wormser’s research. Dr. Barbara Johnson of the CDC and Dr. Gary Wormser, who authored the IDSA guidelines, have jointly published a number of articles supporting this test, which is FDA approved, but performs no better than the two-tiered strategy. So, why is the American public funding C6 research?
And, how do tests the CDC is targeting fare? The IGeneX test is called on in a CDC “warning” issued in February 2005 cautioning against tests that “interpret Western blots using criteria that have not been validated and published in peer-reviewed scientific literature.” IGeneX test reports specify whether the test results meet the CDC interpretation criteria, which requires 5 of 10 IgG bands. However, other studies were able to increase the sensitivity of the test to 93% or higher by using an interpretation requiring 2 of 5 bands. So, IGeneX also reports this information. Why is the CDC ignoring these studies which have a far greater sensitivity?
What about the ALS culture test? The CDC surveillance criteria list “culture test” as an acceptable test, and culture tests are widely regarded as the “gold standard” of testing. As noted above, the ALS test has been validated using the CLIA and CMS requirements. However, it is a relatively new test. A recently published study of the test demonstrated that it had sufficient sensitivity and specificity, but these findings should be confirmed in additional studies. Why isn’t the government funding this type of research?
It’s time for the CDC and the NIH to abandon the failed two-tiered strategy and stop funding tests like the C6, which do no better. Patients want diagnostic tests with greater sensitivity so that patients can get diagnosed and treated. A recent article pegs the number of Lyme tests performed annually at 3.4 million—which translates into a market of roughly $340 million a year. Not only do these numbers suggest that there is a lot more Lyme around than the CDC or IDSA acknowledge, but they also tell us that commercially vested interests and the researchers they consult with may have a stake in keeping the status quo in lab testing regardless of how bad the tests are.Could monetary considerations have something to do with opposition to new lab tests?
The LYME POLICY WONK blog is written by Lorraine Johnson, JD, MBA, who is the Chief Executive Officer of LymeDisease.org, formerly CALDA. Contact her at lbjohnson@lymedisease.org.
Bibliography:
The American Association for Clinical Chemistry, which is a professional association of over 8,000 members concerned with blood diagnostic tests, has an extensive website describing diagnostic lab test validation requirements. Interested readers should check it out.
Centers for Disease Control and Prevention, Lyme disease: Two-step Laboratory Testing Process http://www.cdc.gov/lyme/diagnosistesting/LabTest/TwoStep/index.html
Centers for Disease Control and Prevention. Notice to Readers: Caution Regarding Testing for Lyme Disease. Mmwr. February 11, 2005 February 11, 2005;54((05)):125.
Engstrom SM, Shoop E, Johnson RC. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J. Clin. Microbiol. 33(2), 419–427 (1995).
Kelly, J. Lyme Culture Test Causes Uproar. Medscape (Jan 30, 2013).
Ma B, Christen B, Leung D, Vigo-Pelfrey C. Serodiagnosis of Lyme borreliosis by western immunoblot: reactivity of various significant antibodies against Borrelia burgdorferi. J. Clin. Microbiol. 30(2), 370–376 (1992).
Sapi E, Pabbati N, Datar A, Davies EM, Rattelle A, Kuo BA. Improved culture conditions for the growth and detection of borrelia from human serum. Int J Med Sci. 2013;10(4):362-76.
Shah JS, Du Cruz I, Narciso W, Lo W, Harris NS. Improved clinical sensitivity for detection of antibodies to Borrelia burgdorferi by Western blots prepared from a mixture of two strains of B. burgdorferi, 297 and B31, and interpreted by in-house criteria.European Infect. Dis. 2010;4:56–60.
Stricker RB, Johnson L. Lyme wars: let’s tackle the testing. BMJ. 2007 Nov 17;335(7628):1008.
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