LCD L35062: Biomarkers Overview

Compliance with the provisions in this LCD may be monitored and addressed through post payment data analysis and subsequent medical review audits.

History/Background and/or General Information

The emergence of personalized laboratory medicine has been characterized by a multitude of testing options which may more precisely pinpoint management needs of individual patients. As a result, the growing compendium of biomarkers requires a more careful evaluation by both clinicians and laboratorians as to what testing configurations can more optimally realize the promises of personalized medicine. There are a plethora of burgeoning tools, including both gene-based (genomic) and protein-based (proteomic) assay formats, in tandem with more conventional (longstanding) flow cytometric, cytogenetic, etc. biomarkers. Classified somewhat differently, there are highly diverse approaches ranging from single mutation biomarkers to multiple biomarker platforms, the latter of which often depend upon sophisticated biomathematical interpretative algorithms. This policy will provide guidance on the broad range of (recently coded) biomarkers, and how such a wide array of testing platforms can be best accommodated by this local Medicare Administrative Contractor.

Medicare coverage for screening of those individuals with a family history of certain disease is covered only for a limited number of services as listed in the Section 280 – Preventative and Screening Services of the IOM 100-02, Medicare Benefit Policy Manual , Chapter 15.

Tests performed without relationship to treatment or diagnosis of a patient with no findings or history for a specific illness, symptom, complaint or injury unless set exclusion are so noted in Title 42 CFR, Section 411.15(a)(1).

Local Medicare coverage of such biomarkers must be predicated upon three fundamental principles:

First, there must be an underlying performance of acceptable, high-quality analytical validity for all such laboratory testing. As a result, the laboratory shall have available upon request:

• Analytical and clinical validation reports for Clinical Laboratory Improvement Amendments (CLIA), including the test description, intended use, and indications for testing.

• If applicable, all formal, written minutes and correspondences (including any Q & A and supporting documentation) with the New York State Department of Health (NYSDOH) or the United States (U.S.) Food and Drug Administration (FDA).

• Most recent inspection results (including recommendations) or scheduled inspection(s) from CLIA, College of American Pathologists (CAP), or NYSDOH, as applicable.

Second, there must be an appreciation of evidence-in-transition where new biomarkers should be brought on-line in harmonization with their proven clinical validity/utility (CVU). Although analytical validity is an equally important metric, it remains more outside of a payer's purview to conduct such detailed evaluations. Therefore, in the absence of a standard CVU referee process (e.g., although FDA labeling of biomarkers can be a helpful adjunct, it may not always be relevant), the key imperative is for medical necessity to be reflected by the clear articulation of a particular biomarker niche.

Third, there must be a recognized decision impact of such biomarkers by the clinical community. In other words, there must be acceptance/uptake of specific testing into patient management. It should be taken into account that to reach the medical necessity threshold, such acceptance should be based on the strongest evidence available, ideally from along the spectrum of high-quality masked, randomized controlled clinical trials, and much less preferably from lower levels of evidence, which are predicated upon expert opinion only without primary study data.

Per above, it is relevant to categorize biomarkers into functional clusters which, in turn, can enable longitudinal coverage guidance that is most relevant to the Medicare program mission:

The commercial availability does not ensure that a molecular diagnostic test is indicated for clinical application. Molecular diagnostic testing is a rapidly evolving science in which the significance of detecting specific mutations has yet to be clarified in many circumstances. Analytical and clinical validity as well as clinical utility are the responsibility of the provider, and all testing must meet standards of care.

Covered Indications

1. GERMLINE (HEREDITARY) MUTATIONS

Medicare considers genetic testing medically necessary to establish a molecular diagnosis of an inheritable disease when all of the following criteria are met:

• The beneficiary must display clinical features of an associated disease, but noting that coverage of molecular testing for carrier status or family studies is considered screening and is statutorily excluded from coverage; and

• The result of the test will directly impact the treatment being delivered to the beneficiary; and

• A definitive diagnosis remains uncertain after history, physical examination, pedigree analysis, genetic counseling, and completion of conventional diagnostic studies.

Note: The following two germline hereditary mutation tests will be considered medically reasonable and necessary when performed for evaluation of venous thromboembolism. Refer to ICD-10 Code Group 3 in the related Local Coverage Article: Billing and Coding: Biomarkers Overview A56541.

• Factor II (F2 gene)

• Factor V (F5 gene)

* While not required for payment, NCCN Guidelines recommend referral to a cancer genetics professional with expertise and experience in cancer genetics prior to genetic testing and after genetic testing. Examples of cancer genetics professionals with expertise and experience in cancer genetics include: an American Board of Medical Genetics or American Board of Genetic Counseling certified or board eligible Clinical Geneticist, Medical Geneticist or Genetic Counselor not employed by a commercial genetic testing laboratory (excludes individuals employed by or contracted with a laboratory that is part of an Integrated Health System which routinely delivers health care services beyond just the laboratory test itself as these individuals are also considered independent); medical oncologist, obstetrician-gynecologist or other physician trained in medical cancer genetics, a genetic nurse credentialed as either a Genetic Clinical Nurse or an Advanced Practice Nurse in Genetics by either the Genetic Nursing Credentialing Commission (GNCC) or the American Nurses Credentialing Center (ANCC) who is not employed by a commercial genetic testing laboratory (excludes individuals employed by or contracted with a laboratory that is part of an Integrated Health System which routinely delivers health care services beyond just the laboratory test itself as these individuals are also considered independent).

2. SOMATIC MUTATIONS, ONCOLOGY :

• Please Refer to LCD L35396, Biomarkers for Oncology.

This LCD imposes frequency limitations. For frequency limitations please refer to the Utilization Guidelines section below.

Notice: Services performed for any given diagnosis must meet all of the indications and limitations stated in this policy, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules.

N/A