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.