Genetic (Genomic) Testing

CMS wishes to obtain the MEDCAC’s recommendation regarding the desirable characteristics of evidence that could be used by the Medicare program to determine whether genetic (including genomic) testing as a laboratory diagnostic service improves health outcomes in Medicare beneficiaries. SACGHS has defined genetic testing as “…any test performed using molecular biology methods to test DNA or RNA, including germline, heritable, and acquired somatic variations.”

Medicare may cover a diagnostic test that is used by the beneficiary’s treating physician to guide the physician’s diagnosis and treatment of the beneficiary’s personal condition. This contrasts with a screening test used to identify an occult condition or state in an asymptomatic person. The questions below should be addressed in the former context, i.e. diagnostic testing.

Q1. Are the desirable characteristics of evidence for diagnostic genetic testing different from the desirable characteristics of diagnostic testing in general?

Discussion

Q2. What are the desirable characteristics of evidence for determining the analytical validity of genetic diagnostic tests?

Discussion

Q3. Beyond aspects of analytical validity considered above, are there meaningful differences in the desirable and/or necessary characteristics of evidence about the effect of genetic testing on outcomes for the three testing paradigms below? If yes, please consider question 4 separately for each paradigm. If not, please consider question 4 to apply equally to all three.

• Diagnostic assessment
• Prognostic assessment
• Pharmacogenomic assessment

Q4. For each type of outcome below, how confident are you that methodologically rigorous evidence on the outcome is sufficient to infer whether or not diagnostic genetic testing improves patient centered health outcomes?

For each lettered outcome type, assign a number from 1 to 5 to indicate your vote. A lower number indicates lower confidence; a higher number indicates higher confidence.

1. Changes in physician-directed patient management
2. Indirect or intermediate healthcare outcomes e.g., changes in laboratory test results such as hemoglobin or time to achieve a target value
3. Direct patient-centered healthcare outcome e.g., mortality, functional status, adverse events

Q5. Are there ethical issues particular to genetic testing that may alter the methodologic rigor of studies of genetic testing?

Please discuss the existence, relevance, and impact of such issues.

Q6. Does the age of the Medicare beneficiary population present particular challenges that may compromise the generation and/or interpretation of evidence regarding genetic testing?

Please discuss the existence, relevance, and impact of such issues.

Medicare Evidence Development and Coverage Advisory Committee
Meeting of February 25, 2009: Diagnostic Uses of Genetic Testing

CMS seeks advice from the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) about the basis of evidence for coverage of genetic testing. Each of these two MEDCAC sessions will focus on a separate use of genetic testing:

1. The first, in February 2009, seeks guidance on the types of evidence on which to base coverage decisions relating to diagnostic uses of genetic testing (see examples below) as it may apply to improving health outcomes in the Medicare beneficiary population.
2. The second, tentatively scheduled for May 2009, will focus on screening uses of genetic testing and its potential application to Medicare beneficiaries. Further clarification of specific issues which CMS asks this MEDCAC session to consider will be available later.

CMS considers that a laboratory test is performed for screening if used to detect the presence or the risk of a latent or inapparent disease on a test sample from an individual who does not demonstrate signs or symptoms of the disease. Screening uses of laboratory tests (including genetic tests) are not generally benefits under the Medicare program and thus are ineligible for Medicare coverage unless Congress has specifically directed otherwise..

In Question 3 proposed for MEDCAC consideration, the Committee may wish to consider several uses of genetic testing together or separately:

• Diagnostic assessment: for example, testing for the variant of the gene HD associated with Huntington’s disease;
• Prognostic assessment: for example, assessment of gene expression in tumor tissue to evaluate likelihood of distant recurrence in patients with early-stage breast cancer; and
• Pharmacogenomic assessment: for example, testing for variants in the K-ras gene which indicated absent response to certain chemotherapy for colorectal cancer (e.g., cetuximab).

A table briefly summarizing recent articles on each genetic test cited above is included below.

References:

1. Walker FO. “Huntington’s Disease”. Lancet 2007; 369: 218–28.
2. EGAPP Working Group. “Recommendations from the EGAPP Working Group: can tumor gene expression profiling improve outcomes in patients with breast cancer?” Genet Med 2009 January; 11(1): 66-73.
3. Allegra CJ, Jessup JM, Somerfield MR, et al. “American Society of Clinical Oncology Provisional Clinical Opinion: Testing for KRAS Gene Mutations in Patients with Metastatic Colorectal Carcinoma to Predict Response to Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Therapy”. American Society of Clinical Oncology, Alexandria, VA, 2008. Downloaded on 1/21/2009 from www.asco.org.