June 14, 2001 - FDA Blood Products Advisory Committee: Clinical Laboratory Improvement Act (CLIA) Criteria for In Vitro Diagnostic Tests: Applicability of Waivers to HIV Rapid Tests

The American Society for Microbiology (ASM) appreciates the opportunity to submit comments to the Food and Drug Administration's (FDA) Blood Products Advisory Committee regarding the issue of waiving HIV rapid tests from certain requirements of the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The ASM is the largest single life science society in the world with more than 42,000 members representing a broad spectrum of subspecialties, including microbiologists who work in biomedical, clinical, public health, and industrial laboratories. The mission of ASM is to enhance the science of microbiology to better understand basic life processes and to promote the application of this knowledge for improved health and well-being.

Twenty years ago, the acquired immunodeficiency syndrome (AIDS) was first recognized. In the intervening period, the medical, social and economic manifestations of this devastating disease have become well known. In recognition of the increasing worldwide pandemic, and the need to reach new populations at risk (women, children, racial and ethnic minorities, and those living in rural and small urban areas), ASM supports the development and licensing of rapid, sensitive, and specific diagnostic tests for HIV infection. It also supports efforts to review current AIDS strategies to arrest the spread of HIV infection. However, it must be recognized that erroneous diagnostic test results - false negatives or false positives - will have catastrophic consequences. Infected patients could be undiagnosed and could continue to represent an unrecognized reservoir of infection; non-infected patients would suffer the emotional trauma associated with the diagnosis of this potentially fatal infection. It could be said that no other laboratory test is weighted more seriously than one for the diagnosis of an HIV infection.

It is for this reason that ASM opposes waiving HIV rapid tests from CLIA regulation. Granting such a waiver would undermine the purpose of CLIA in providing safe and high quality laboratory testing. The intent of CLIA to provide waiver from regulation is only for those tests that feature the most simple and basic of testing mechanisms, not for moderate and high complexity tests such as HIV antibody tests. HIV rapid tests require quality control, proficiency testing and confirmatory testing to validate results. It is important to point out that even though waived tests are deemed simple to perform, erroneous results are possible and can be devastating. Furthermore, the fact that rapid tests can produce a result within 15 to 20 minutes has no impact on its complexity categorization.

The ASM's comments are consistent with the Food and Drug Administration Modernization Act of 1997 (FDAMA) which defines waived tests as "laboratory examinations and procedures that have been approved by the Food and Drug Administration for home use or that, as determined by the Secretary, are simple laboratory examinations and procedures that have an insignificant risk of an erroneous result, including those that:

(A) employ methodologies that are so simple and accurate to render the likelihood of erroneous results by the user negligible, or

(B) the Secretary has determined pose no unreasonable risk of harm to the patient if performed incorrectly."

Although it is conceivable that a simple and accurate test can be developed, it should be noted that currently, all positive HIV antibody screening tests performed in clinical laboratories are repeated in duplicate and confirmed as positive by a more specific test method. Clearly, the accuracy of tests performed by certified medical personnel still requires appropriate oversight. In addition, it must be recognized that an HIV test performed incorrectly cannot be classified as one that "poses no unreasonable risk of harm to the patient" or to the contacts of the patient.

ASM's concern about the FDA's consideration of HIV rapid tests for CLIA waiver is further heightened by recent studies conducted by the Health Care Financing Administration (HCFA). Approximately 74% of registered laboratories have Certificates of Waiver (COW) or Provider-Performed Microscopy (PPMP) Certificates, and therefore, no government oversight. According to HCFA's pilot study of COW and PPMP laboratories in Ohio and Colorado, 50% of such laboratories frequently failed to follow current manufacturers' instructions or had deficiencies in the area of quality control. HCFA's expanded survey of COW and PPMP laboratories in eight additional states conducted between October 2000 and January 2001, noted similar problems of the same magnitude.

With the lack of quality control and adherence to manufacturer's instructions documented by the HCFA study, there is no guarantee that untrained users of a waived test will seek confirmatory tests to verify positive test results or even inform the individual tested of the significance of the result, whether it be positive or negative. Without CLIA-mandated quality control, proficiency testing and personnel standards, there is no mechanism for assuring that tests are being performed correctly. Tests conducted in unregulated environments cannot provide patients and health care professionals with the same degree of assurances as those tests conducted in environments subject to quality control, proficiency testing, confirmatory testing, and the availability of professional counseling. The CLIA waived category does not provide a mechanism to assure this.

Alternative approaches under CLIA, such as "limited public health use," is an avenue that should be considered by the FDA and the Blood Products Advisory Committee. This would improve access to testing as well as provide for the proper oversight as required for non-waived tests.

Prompt diagnosis of HIV and accessibility of testing is critical to the effective treatment of HIV infected patients. Testing must be safe, valid, reliable, and meaningful for patients and health care providers. Emphasis should be placed on the safety and the accuracy (defined as a comparison with a reference method) of HIV test results to ensure that appropriate patient care is provided to tested individuals.