Proposed LCD - MolDX: Molecular Testing for Solid Organ Allograft Rejection (DL38582)

CMS National Coverage PolicyTitle XVIII of the Social Security Act (SSA), 1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary42 CFR 410.32(a) Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: ConditionsCMS Internet-Only Manuals, Pub. 100-02, Medicare Beneficiary Policy Manual, Chapter 15, 80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, and Other Diagnostic Tests, 80.1.1 Certification ChangesCoverage Indications, Limitations, and/or Medical NecessityDEFINITIONSFor purposes of this policy the following definitions are used:Surveillance (Protocol)  patient is asymptomatic; no clinical signs or symptoms of organ injury/rejection.For-Cause  patient has clinical signs or symptoms of organ injury/rejection.AR  Acute RejectionACR  Acute Cellular RejectionAMR  Antibody-Mediated RejectionAV  Analytical ValidityCV  Clinical ValidityOPTN - Organ Procurement and Transplantation NetworkGEP  Gene Expression Profilingdd cfDNA  Donor-Derived Cell-Free DNAThis Medicare contractor will provide limited coverage for molecular diagnostic tests used in the evaluation and management of patients who have undergone solid organ transplantation. These tests can inform decision making along with standard clinical assessments in their evaluation of organ injury for active rejection (AR).These tests may be ordered by qualified physicians considering the diagnosis of AR, helping to rule in or out this condition when assessing the need for or results of a diagnostic biopsy.They should be considered along with other clinical evaluations and results and may be particularly useful in patients with significant contraindications to invasive procedures.Molecular diagnostic tests that assess a transplanted allograft for rejection status are covered when ALL of the following criteria are met:The test must provide information about at least one of the two following clinical status determinations:AR statusCellular or Antibody-mediated rejection (ACR or AMR) statusThe intended use of the test must be to inform clinical decision making as per the following:To assist in the evaluation of adequacy of immunosuppression, wherein a non-invasive or minimally invasive test can be used in lieu of a tissue biopsy in a patient for whom information from a tissue biopsy would be used to make a management decision regarding immunosuppression, ORAs a rule-out test for AR in validated populations of patients with clinical suspicion of rejection with a non-invasive or minimally invasive test to make a clinical decision regarding obtaining a biopsy, ORFor further evaluation of allograft status for the probability of allograft rejection after a physician-assessed pretest, ORTo assess rejection status in patients that have received a biopsy, but the biopsy results are inconclusive or limited by insufficient material.Therefore, molecular diagnostic tests are not covered if the results will not inform clinical decision making (for example if the patient has undergone a recent biopsy with a definitive diagnosis or has a planned upcoming biopsy that will be performed regardless of the result of the molecular test). Similarly, if a molecular test is performed as a result of findings from a pre-test, this suggests that the molecular test is informed by and performed after the results of the pre-test are known; as such, the molecular tests should be performed after the relevant pre-test(s).IF the molecular diagnostic test is performed in-lieu of a surveillance (protocol) biopsy, the testing frequency must be no more frequent than the OPTN center-specific surveillance biopsy schedule.The test demonstrates analytical validity (AV), including an analytical and clinical validation for any given measured analytes, and has demonstrated equivalence or superiority for sensitivity or specificity (depending on intended use) of detecting allograft rejection to other already-accepted tests for the same intended use measuring the same or directly comparable analytes.Clinical validity (CV) of any analytes (or expression profiles) measured must be established through a study published in the peer-reviewed literature for the intended use of the test in the intended population. The degree of validity must be similar or superior to established and covered tests (see associated coverage Articles). If conducted with concordance to tissue histologic evaluation the most current Banff Classification for renal allografts or other accepted criteria (if existing) for other organs must be used.The test is being used in a patient who is part of the population in which the test was analytically validated and has demonstrated CV.For a given patient encounter, only one molecular test for assessing allograft status may be performed.For minimally or non-invasive tests, the benefit to risk profile of the molecular test is considered by the ordering clinician to be more favorable than the benefit to risk profile of a tissue biopsy, or a tissue biopsy cannot be obtained. For example, this may be the case if a biopsy is considered medically contraindicated in a patient.The test successfully completes a Molecular Diagnostic Services Program (MolDX) Technical Assessment that will ensure that AV, CV, and clinical utility criteria set in this policy are met to establish the test as Reasonable and Necessary.Covered tests with AV that is significantly below similar services may have coverage rescinded.General InformationAssociated InformationN/ASources of InformationN/ABibliography