Edward McCabe, MD, PhD
Secretary's Advisory Committee
on Genetic Testing
National Institutes of Health
9000 Rockville Pike, Building 1, Room 103
Bethesda, Maryland 20892

Dear Chairman McCabe:

The American Association for Clinical Chemistry (AACC) welcomes the opportunity to comment on the Secretary's Advisory Committee on Genetic Testing's (SACGT's) December 7, 2000 request for public input on its proposed test classification methodology for genetic testing. In general, AACC supports the broad objectives of the panel, namely to ensure that patients and clinicians are fully informed about the limitations, as well as the benefits of genetic tests, and that the tests actually measure what the manufacturer or laboratory claims that they do. AACC is not convinced, however, that the proposed model outlined in the December 7th notice achieves these objectives.

Level of Review
AACC agrees that any regulatory model should be simple and easy to implement. However, we are concerned that the current approach is so narrowly constructed that it does not differentiate between those tests that are of higher and lesser risks. Some factors that could be used to separate the tests include its intended use, availability of therapy, disease incidence, disease progression, availability and strength of confirmatory procedures, and reliability of clinical corroboration, among others. We also recommend that the differences between Level I and Level II be further delineated. It is difficult to evaluate the effectiveness of the framework, when the requirements for the two levels do not seem to differ greatly.

Recommended Criteria
AACC supports the use of "analytical validity" as the threshold criterion. Moreover, AACC opposes specific thresholds or minimum standards for the components of analytical validity. Thus, the analytical sensitivity and analytical specificity requirements should be flexible depending on the characteristics of the test and the disease. AACC believes that any attempt to establish stringent thresholds would defeat the intended purpose of the classification scheme by precluding "new and innovative oversight mechanisms" for genetic testing.

Also, we recommend that SACGT further define how population screening would be utilized for determining the level of scrutiny. There are many tests that can be used for both diagnostic and population screening purposes. If a new test is initially used for diagnostic purposes, but later used for population screening, would that trigger an additional FDA review?

Similary, for frequency of disease, there is a strong association between disease prevalence and race and ethnicity. How will SACGT address these variations? For example, the prevalence of cystic fibrosis (CF) is approximately 1/2000 in Northern Europeans, 1/5000 in African Americans and even less frequent among Asian and Native Americans. Thus, a CF test could be classified as rare or common depending on which prevalence data are used.

Refine and Re-propose
AACC suggests that SACGT:

  • continue to work with HCFA and CDC as they attempt to refine the CLIA standards;
  • continue to work the FDA, which is currently examining these very issues; and
  • re-propose a more detailed proposal for comment.

By way of background, AACC is the principal association of professional laboratory scientists--including MDs, PhDs and medical technologists. AACC's members develop and use chemical concepts, procedures, techniques and instrumentation in health-related investigations and work in hospitals, independent laboratories and the diagnostics industry nationwide. The AACC's objectives are to further the public interest and educational activities and to help maintain high professional standards.

If you have any questions or we may be of any assistance, please call me at (215)662-6575 or Vince Stine, Director, Government Affairs, at (202) 835-8721.


Larry Kricka, D.Phil., F.A.C.B.,
C.Chem., F.R.S.C., F.R.C.Path.

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