TO: Administrative File: CAG-00455N
FROM: Tamara Syrek Jensen, JD
Director, Coverage and Analysis Group
Joseph Chin, MD, MS
Deputy Director, Coverage and Analysis Group
Melissa Evans, PhD, MSAE
Director, Division of Policy and Evidence Review
Lori Ashby, MA
Deputy Director, Division of Policy and Evidence Review
Heather Hostetler, JD
Lead Analyst
Joseph Dolph Hutter, MD, MA
Lead Medical Officer
SUBJECT: Proposed decision memorandum for AlloMap® Molecular Expression Testing for Detection of Rejection of Cardiac Allografts
DATE: 10/16/2020
I. Proposed Decision
The Centers for Medicare & Medicaid Services (CMS) is proposing to not issue a National Coverage Determination (NCD) for AlloMap® Molecular Expression Testing for Detection of Rejection of Cardiac Allografts.
In the absence of an NCD, coverage determinations for AlloMap® Molecular Expression Testing for Detection of Rejection of Cardiac Allografts, under section 1862(a)(1)(A) of the Social Security Act (the Act) and any other relevant statutory requirements, will continue to be made by the local Medicare Administrative Contractors (MACs).
II. Background
AlloMap® Molecular Expression (AlloMap®) Testing is an FDA-approved In Vitro Diagnostic Multivariate Index Assay (IVDMIA) test service performed in a single laboratory, assessing the gene expression profile of ribonucleic acid (RNA) isolated from peripheral blood mononuclear cells (PBMC). AlloMap® Testing is intended to give physicians information on the risk of acute cellular rejection in their patients following heart transplant. AlloMap® is one type of non-invasive diagnostic test that may be used to identify patients who have a low probability of moderate/severe acute cellular rejection at the time of testing. Physicians can use results of this test in conjunction with standard clinical assessment to identify which post-transplant patients should undergo heart biopsy.
AlloMap® received market clearance from the Food and Drug Administration on August 26, 2008 and is indicated for use in heart transplant recipients who are 15 years of age or older and at least 2 months (≥55 days) post-transplant.
Throughout this document we use numerous acronyms, some of which are not defined as they are presented in direct quotations. Please find below a list of these acronyms and corresponding full terminology:
ACR – Acute cellular rejection
CMS - Centers for Medicare & Medicaid Services
FDA - Food and Drug Administration
IVDMIA - In Vitro Diagnostic Multivariate Index Assay
MAC - Medicare Administrative Contractor
NCA - National Coverage Analysis
NCD - National Coverage Determination
PBMC - Peripheral blood mononuclear cells
RNA - Ribonucleic Acid
US - United States
III. History of Medicare Coverage
Prior to this national coverage analysis, CMS did not have an NCD specific to AlloMap® Molecular Expression Testing for Detection of Rejection of Cardiac Allografts. In the absence of an NCD, coverage decisions are made by local MACs.
A. Current Request
We received a complete, formal request in January 2013 from Marc Halushka MD, PhD, Department of Pathology, Johns Hopkins Medical Institutions to make a national coverage determination to non-cover AlloMap® Molecular Expression Testing for Detection of Rejection of Cardiac Allografts. The requestor stated that generally a blood-based assay to detect acute cellular rejection and antibody-mediated rejection in individuals would benefit patients and be a significant improvement in diagnosis and treatment, given the limitations and risks of the more invasive heart biopsy. However, the requestor believed based on the evidence included in the request, that this particular assay "does not perform adequately." Specifically, it has "poor sensitivity," "no intrinsic predictive capability," and "is useful in only a small percentage of Medicare patients." The formal request letter can be viewed via the tracking sheet for this NCA on the CMS website at: http://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id302.pdf.
B. Benefit Category
Medicare is a defined benefit program. For an item or service to be covered by the Medicare program, it must fall within one of the statutorily defined benefit categories outlined in the Act. The benefit category is diagnostic tests, X-rays, & clinical laboratory services
IV. Timeline of Recent Activities
| Date |
Action |
| October 16, 2020 |
CMS initiates this national coverage analysis and posts the proposed decision memorandum. A 30-day public comment period begins. |
V. Public Comment
CMS will respond to the public comments on this proposed decision when issuing the final decision memorandum.
VI. CMS Analysis
The term "national coverage determination" is defined by statute and means a determination by the Secretary of the Department of Health and Human Services (Secretary) with respect to whether or not a particular item or service is covered nationally under Title XVIII of the Act. NCDs are controlling authorities for Medicare contractors and adjudicators as described more fully in 42 CFR 405.1060.
In the absence of an NCD, Medicare contractors may establish a local coverage determination (LCD) (defined in section 1869(f)(2)(B) of the Act) or adjudicate claims on a case-by-case basis. The case-by-case adjudicatory model permits consideration of a beneficiary's particular factual circumstances described in the medical record. The case-by-case model affords more flexibility to consider a particular individual's medical condition than is possible when the agency establishes a generally applicable rule.
With relatively few exceptions, the statute provides in section 1862(a)(1) of the Act that no payment may be made under Part A or Part B for any expenses incurred for items or services which "are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member." The Supreme Court has recognized that "[t]he Secretary's decision as to whether a particular medical service is ‘reasonable and necessary’ and the means by which she implements her decision, whether by promulgating a generally applicable rule or by allowing individual adjudication, are clearly discretionary decisions." Heckler v. Ringer, 466 U.S. 602, 617 (1984). See also, Almy v. Sebelius, 679 F.3d 297, 303-04 (4th Cir. 2012) ("The Medicare statute preserves this discretion for the Secretary, leaving it to her judgment whether to proceed by implementing an NCD, by allowing regional contractors to adopt an LCD, or by deciding individual cases through the adjudicative process."); International Rehabilitative Services Inc. v. Sebelius, 688 F.3d 994, 1001 (9th Cir. 2012) ("But while the agency may make coverage determinations via up-front rules, it is not required to do so; rather, the agency has discretion in whether to make coverage determinations by up-front rulemaking or by case-by-case adjudication.")
We believe the proposed decision to continue to allow MACs to determine coverage of AlloMap® Molecular Expression Testing for Detection of Rejection of Cardiac Allografts is clinically appropriate and in the best interest of beneficiaries. Since 2013, when we received the request to open an NCD to non-cover AlloMap, there have been at least three new studies published in the peer-reviewed medical literature evaluating the test (Deng 2014, Kobashigawa 2015, Crespo-Leiro 2015).1 Two of these studies focus specifically on the predictive capabilities of the test (Deng 2014, Crespo-Leiro 2015). While each study has limitations, collectively they demonstrate that use of the test may better allow physicians to select patients who should undergo post-transplant heart biopsy. Thus there is evidence that for some Medicare beneficiaries in certain clinical scenarios, use of the test may be reasonable and necessary under Section 1862(a)(1)(A) of the Act. Due to the very low number of tests, which are used by << 1 percent of the Medicare population, and the need for careful patient selection, CMS believes that coverage of AlloMap is an appropriate determination made by the Medicare Administrative Contractors (MACs). The MACs are structured to be able to take into account local patient, clinician and institutional factors, which are important when the overall prevalence is low.
VII. Conclusion
The Centers for Medicare & Medicaid Services (CMS) is proposing to not issue a National Coverage Determination (NCD) for AlloMap® Molecular Expression Testing for Detection of Rejection of Cardiac Allografts.
In the absence of an NCD, coverage determinations for AlloMap® Molecular Expression Testing for Detection of Rejection of Cardiac Allografts, under section 1862(a)(1)(A) of the Social Security Act (the Act) and any other relevant statutory requirements, will continue to be made by the local Medicare Administrative Contractors (MACs).
[1] Deng MC, Elashoff B, Pham MX, et al. Utility of Gene Expression Profiling Score Variability to Predict Clinical Events in Heart Transplant Recipients. Transplantation. 2014;97(6).
Kobashigawa J, Patel J, Azarbal B, et al. Randomized pilot trial of gene expression profiling versus heart biopsy in the first year after heart transplant: early invasive monitoring attenuation through gene expression trial. Circ Heart Fail. 2015;8(3).
Crespo-Leiro MG, Stypmann J, Schulz U, et al. Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients. BMC Cardiovasc Disord. 2015;15(120).
