Issue:
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 the screening use of genetic testing improves health outcomes or leads to early detection of clinically inapparent disease. The Secretary’s Advisory Committee on Genetics, Health and Society (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.”
Pursuant to Title XVIII of the Social Security Act (the Act), §1862(a)(1)(A), Congress gave the Secretary of Health and Human Services the authority to consider Medicare coverage of diagnostic tests. Diagnostic tests are used by the treating physician to diagnose or treat a condition or disease when the beneficiary has signs or symptoms of a disorder. In contrast to diagnostic tests, screening tests are administered to asymptomatic individuals for the prevention or early detection of illness or disability. During the last 25 years, Congress has added some screening services that are now covered by Medicare; and these screening services include: mammography, glaucoma, pelvic exam and pap test, diabetes, lipids, colorectal cancer and prostate cancer.
Recently, the Medicare Improvements for Patients and Providers Act of 2008 (MIPPA) (Pub. L. 110-275) was approved by Congress. Effective January 1, 2009, MIPPA, section 101(a), provides for Medicare Part B coverage for additional preventive services, that are not already described in Title XVIII of the Act, when the Secretary determines through the national coverage determination (NCD) process (as described in section 1869(f)(1)(B) of the Act) that a new service meets the following statutory requirements for coverage.
(1) The service is reasonable and necessary for the prevention or early detection of an illness or disability;
(2) The United States Preventive Services Task Force (USPSTF) provides a grade A or B recommendation for the service. (The USPSTF recommendations are located at: http://www.ahrq.gov/clinic/uspstfix.htm); and
(3) The service is appropriate for beneficiaries entitled to benefits under Part A or enrolled under Part B.
Currently, Medicare does not have a national coverage decision for screening genetic tests. Since screening is conducted on asymptomatic individuals, the analytic framework for screening tests involves consideration of several different factors compared to diagnostic tests and therapeutic interventions. One framework for evaluating screening tests was outlined by Cochrane and Holland (1971) as follows: “The value of a screening test may be assessed according to the following criteria:
i. Simplicity. In many screening programmes more than one test is used to detect one disease, and in a multiphasic programme the individual will be subjected to a number of tests within a short space of time. It is therefore essential that the tests used should be easy to administer and should be capable of use by para-medical and other personnel.
ii. Acceptability. As screening is in most instances voluntary and a high rate of co-operation is necessary in an efficient screening programme, it is important that tests should be acceptable to the subjects.
iii. Accuracy. The test should give a true measurement of the attribute under investigation.
iv. Cost. The expense of screening should be considered in relation to the benefits resulting from the early detection of disease, i.e., the severity of the disease, the advantages of treatment at an early stage and the probability of cure.
v. Precision (sometimes called repeatability). The test should give consistent results in repeated trials.
vi. Sensitivity. This may be defined as the ability of the test to give a positive finding when the individual screened has the disease or abnormality under investigation.
vii. Specificity. This may be defined as the ability of the test to give a negative finding when the individual screened does not have the disease or abnormality under investigation.”
An example of a genetic test suggested for screening use is detection of the homozygous presence of e4 allele of the APOE gene (also expressed as APOE e4/e4). This genetic characteristic has been shown in published studies to be associated with an elevated risk of developing Alzheimer disease (Odds Ratio 2.1 (95% CI, 5.1-11.9)b). A further discussion of considerations for using this genetic test in a specific clinical scenario is provided in the series of recent articles.
Reference: Attia J, Ioannidis JPA, Thakkinstian A, McEvoy M, Scott RJ, Minelli C, et al. How to use an article about genetic association:
A: background concepts. JAMA 2009 Jan 7; 301(1): 74-81;
B: Are the results of the study valid? JAMA 2009 Jan 14; 301(2): 191-7;
C: What are the results and will they help me in caring for my patients? JAMA Jan 21; 301(3): 304-8.
Questions:
The following questions should be addressed in the context of screening genetic tests for the early detection of disease:
Q1. Are there differences in the desirable characteristics of evidence about screening genetic tests versus those of screening tests in general?
Discussion
Q2. What are the desirable characteristics of evidence for determining the analytical validity of screening genetic tests?
Discussion
Q3A. Beyond aspects of analytical validity, are there meaningful differences in the desirable and/or necessary characteristics of evidence about the effect of genetic testing on outcomes? If yes, please consider question 3 separately for each paradigm.
- Early detection of disease in an asymptomatic person
- Early treatment of disease (before signs or symptoms are apparent)
Q3B. What comparative data are needed on alternative strategies for screening?
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 screening genetic testing is effective for the prevention or early detection of illness or disability?
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.
a) Additional (confirmatory) diagnostic procedure
b) Survival
c) Other patient-focused healthcare outcomes e.g., functional status, incidence of adverse events
Q5. What are the desirable measures of the cost-effectiveness of screening genetic tests for the prevention or early detection of illness or disability?
Consider ranking (1=lowest thru 3=highest) the below (a-c) options and/or identify other measures that would be appropriate.
a) Quality-adjusted life years (QALYs) gained due to screening?
b) Decreases in incidence of illness or disability, or net gains in other patient-focused healthcare outcomes?
c) Net changes in lifetime costs of illness or disability?
For discussion.
Q6. What are the desirable methodological characteristics of studies of cost-effectiveness for screening genetic tests for the prevention or early detection of illness of disability?
For discussion.
Q7. Are there ethical issues particular to screening genetic testing that may alter the methodologic rigor of studies of genetic testing?
Please discuss the existence, relevance, and impact of such issues.
Q8. 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 challenges.
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