LCD Reference Article Response To Comments Article

Response to Comments: Pharmacogenomic Testing

A59982

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Source Article ID
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Article ID
A59982
Original ICD-9 Article ID
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Article Title
Response to Comments: Pharmacogenomic Testing
Article Type
Response to Comments
Original Effective Date
07/13/2025
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As an important part of Medicare Local Coverage Determination (LCD) development, National Government Services solicits comments from the provider community and from members of the public who may be affected by or interested in our LCDs. The purpose of the advice and comment process is to gain the expertise and experience of those commenting.

We would like to thank those who suggested changes to the Pharmacogenomic Testing LCD. The official notice period for the final LCD begins on May 29, 2025, and the final determination will become effective on July 13, 2025.

Response To Comments

Number Comment Response
1

The Association for Molecular Pathology (AMP) commented, “AMP appreciates your recognition of the importance of providing coverage to Medicare beneficiaries for pharmacogenomic (PGx) testing. We greatly appreciate that DL 39995 directly refers to the Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines as meeting the necessary criteria for rigorous, standardized evaluation of PGx testing. AMP believes a benefit of crafting the coverage policy to specifically reference CPIC guideline level A or B, as well as the Food and Drug Administration (FDA) table of known gene-drug interactions and FDA labeling will allow coverage to evolve along with the science. We strongly urge you to continue to refer to these evidence sources for demonstrating actionability in clinical decisions in the final LCD.”

NGS appreciates your kind words and support for Pharmacogenomic Testing coverage, based on CPIC and FDA guideline tables of gene-drug pairs.

2

The Association for Molecular Pathology (AMP) further commented as follows:

  1. The removal of the "once per lifetime" restriction on pharmacogenomic (PGx) tests
  2. The addition of CYP3A4 to the relevant gene and drug associations in Billing Article due to its impact on drugs like quetiapine.
  3. The specification of gene names for Tier 2 Molecular Pathology codes 81401 and 81406 in Groups 15 and 16. 
  4. The updating nomenclature to reflect that IFLN3 and IFLN4 refer to the same intragenic variant; and 
  5. The inclusion of additional ICD-10 codes (F90.0, Z94.2, Z94.3, Z94.81, Z94.82, Z94.83)



NGS appreciates your submission of five thoughtful and succinct recommendations to which NGS responds according to the numbering of comments above:

  1. Thank you for the comment. The intent was not to limit PGx testing as the language is interpreted, but rather to address duplicate germline testing. We have added clarification in the finalized LCD and Article.
  2. Thank you for the comment. NGS disagrees at this time, due to the “provisional” status of CPIC’s determination. The intent is for coverage to evolve as the science evolves.
  3. Thank you for your request. Due to system constraints, the adjudication of specific gene/drug pairs automatically is not possible. CPT codes 81401 and 81406 require individual review. We suggest provision of the gene-drug pairing be placed in the Comment field in order to facilitate processing.
  4. NGS disagrees with revision of the nomenclature to reflect that IFLN3 and IFLN4 refer to the same intragenic variant at this time due to the current CPIC Table structure.
  5. The ICD-10-CM diagnosis codes Z94.0 through Z94.9 will not be added at this time.



3

The Dartmouth Cancer Center requested the inclusion and coverage of DPYD gene pharmacogenomic testing to provide necessary coverage to facilitate safer, individualized dosing regimens and improve patient outcomes in gastrointestinal cancers.



Thank you for your comment. NGS agrees and as indicated in the proposed policy, coverage for DPYD testing is provided, based on the Indications and Limitations of Coverage described in the Local Coverage Determination.

4

Dana-Farber Cancer Institute requested the addition of ICD-10-CM codes to Group 7 in the Billing and Coding Article to include code ranges: head and neck (C00-C14), esophagus (C15), stomach (C16), small intestine (C17), colon and rectum (C18-C21), biliary tract (C22-C24), pancreas (C25), female reproductive system (C53-C56), breast (C50), and neuroendocrine neoplasms (C7A). consistency across LCDs.

NGS agrees and will add the ICD-10-CM code ranges accordingly.

5

Brown University Health provided the following comments:

  1. Please remove the requirement that ordering providers must have diagnostic abilities, as PGx testing is utilized post-diagnosis to guide pharmacotherapy. 
  2. Add history of liver transplant to the limitations section, given that recipient DNA does not reflect donor liver metabolism, affecting test validity. 
  3. Clarify billing and coding specifics for multi-gene tests under CPT 81418, ensuring appropriate coding guidance.
  4. Suggests eliminating the need to submit medication names with claims to reduce operational burdens.
  5. Recommends including CPT code 81418 across all relevant groups with stipulations on gene inclusion and proposes adjustments to Table 2 for belzutifan by separating genes into individual rows and assigning appropriate CPT and ICD-10 codes.
  6. Assign ABCG2 (CPT 81479) to a group with associated ICD-10 codes for rosuvastatin and adding medications like metoprolol, tamsulosin, and Auvelity linked to CYP2D6.

 

Thank you for your comments. The responses are numbered to reflect each comment above.

  1. The ordering provider should be the qualified person who will treat the patient with the medications in question. In addition, the ordering provider of a PGx test is restricted to providers who have the licensure, qualifications, and necessary experience/training to both diagnose the condition being treated and also to prescribe medications (the provider must be able to do both) for the condition either independently or in an arrangement as required by all the applicable state laws. 
  2. Thank you for your recommendation. NGS agrees, and Z90.4 is automatically included in the “ICD-10-CM Codes that DO NOT Support Medical Necessity” section. 
  3. We have provided clarifying language in the policy regarding multi-gene tests under CPT code 81418. 
  4. Thank you for your request. Due to system constraints, the adjudication of specific gene/drug pairs automatically is not possible. We require the provision of the specific drug be placed in the Comment field in order to facilitate processing.
  5. Table 2 includes the specific genes indicated by the FDA for belzutifan. NGS will add the following asterisked ICD-10-CM code to support medical necessity: Q85.83*.
  6. The addition of gene-drug pairs will be evaluated, based on CPIC and FDA levels of evidence.

 

6

The American Academy of Dermatology Association and the Dermatology Contractor Advisory Committee (DermCAC) recommended revising the "Provider Qualifications" section of the Local Coverage Determination (LCD) to state that the ordering provider "must be the treating clinician who is responsible for the management of the patient’s condition and/or coordinating care with such clinician."

 

Thank you for your comment. Please see response 5, number one.

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Associated Documents

Medicare BPM Ch 15.50.2 SAD Determinations
Medicare BPM Ch 15.50.2
Related Local Coverage Documents
LCDs
L39995 - Pharmacogenomic Testing
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