Coverage criteria policies

These services may or may not be covered by your HealthPartners plan. Please see your plan documents for your specific coverage information. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage.

Prior authorization is required for pharmacogenetic testing, except for the following services when associated with procedure and primary diagnosis codes from the list below (under Codes):

• BRCA1/2 genotyping related to olaparib or rucaparib therapy
• CFTR genotyping related to ivacaftor or lumacaftor therapy
• CYP2D6 genotyping related to eliglustat or tetrabenazine therapy
• HLA-B*1502 genotyping related to carbamazepine or phenytoin therapy
• HLA-B*5701 genotyping related to abacavir therapy
• HLA-B*5801 genotyping related to allopurinol therapy

Medication coverage is outside the scope of this coverage policy.

For somatic testing related to cancer, see the Genetic Testing: Molecular Profiling for Cancer Management coverage policy.

Pharmacogenetic testing other than as described below is subject to a review for medical necessity, based on current clinical literature and expert recommendations, unless listed as an indication that is not covered.

Indications that are covered

• BRCA1/2 genotyping related to olaparib or rucaparib therapy
• CFTR genotyping related to ivacaftor or lumacaftor therapy
• CYP2D6 genotyping related to eliglustat or tetrabenazine therapy
• HLA-B*1502 genotyping related to carbamazepine or phenytoin therapy
• HLA-B*5701 genotyping related to abacavir therapy
• HLA-B*5801 genotyping related to allopurinol therapy
• DPYD genotyping related to fluoropyrimidine (fluorouracil or capecitabine) therapy in members with unusually early, severe, treatment-related toxicity in the first few therapy cycles
• TPMT genotyping related to 6-mercaptopurine or azathioprine therapy for inflammatory bowel disease
• TYMS genotyping related to fluoropyrimidine (fluorouracil or capecitabine) therapy in members with unusually early, severe, treatment-related toxicity in the first few therapy cycles
• UGT1A1 genotyping related to irinotecan therapy in members with elevated serum bilirubin or Gilbert syndrome

Indications that are not covered

1. Genetic testing is not covered and is considered not medically necessary when test results will not directly impact the treatment or management of a condition or provide a unifying diagnosis for a previously unidentified condition because the testing is not expected to restore or maintain the member’s health, prevent deterioration of the member’s condition, nor prevent the reasonably likely onset of a health problem or detect an incipient problem.
2. The following services are not covered and are considered not medically necessary because they are not within the practice parameters of the general medical community:
1. Comparative analysis using short tandem repeat (STR) markers, which is considered integral to the primary procedure and ineligible for separate coverage
2. Direct-to-consumer genetic testing
3. Genetic testing for acquired disorders (those of non-genetic etiology, such as a condition caused by an identified environmental factor).
4. Genetic testing which was not ordered by a licensed healthcare provider or physician (see Definitions) who has established a direct patient care relationship with the member to be tested.
5. Genetic testing that is provided solely to satisfy data collection and analysis needs and that will not be used in direct clinical management.
3. Repeat testing of a unique analyte using the identical method of analysis is not covered and is considered not medically necessary because it is not considered an appropriate frequency of care.
4. Multiple-gene panels which include genes not associated with the specific condition, features, characteristics, or symptoms under evaluation, or including genes not associated with conditions within the ordering provider’s differential diagnosis list for the affected member, are not covered and are considered not medically necessary because they are not considered an appropriate type of service for the member’s condition.
5. The following services are considered experimental/investigational because reliable evidence does not permit conclusions concerning safety, effectiveness, or effect on health outcomes:
1. APOE genotyping
2. COMT genotyping
3. KIF6 genotyping
4. MTHFR genotyping
5. NUDT15 genotyping
6. Serotonin receptor (HTR2A and HTR2C) genotyping
7. SLCO1B1 genotyping
8. VKORC1 genotyping
9. Genotyping of CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP2B6, CYP1A2, or of any other gene in the Cytochrome p450 (CYP450) families for any indication except as described under Indications that are Covered
10. Multiple-gene pharmacogenetic panels for all indications, including, but not limited to, multiple-gene panels involving one or more genes from the Cytochrome p450 (CYP450) families
11. Pharmacogenetic testing to inform the selection or dose of medication therapy for management of depression, mood disorders, psychosis, anxiety, attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD), and/or substance use disorder

Cytochrome P450 (CYP450) includes multiple genes which affect the metabolism of a variety of drug classifications.

Genotyping is the process of determining which genetic variants an individual possesses.

Healthcare provider is any licensed non-physician (excluding naturopathic providers).

Pharmacogenetic tests (pharmacogenomic tests) analyze genes to identify patients who are likely to respond to a specific drug, those who may not respond, and those likely to have adverse reactions.

Physician is a licensed medical doctor or doctor of osteopathy.

If available, codes for a procedure, device or diagnosis are listed below for informational purposes only, and do not guarantee member coverage or provider reimbursement. The list may not be all inclusive.

These services do not require prior authorization when associated with pharmacogenetic testing:

These services do not require prior authorization when associated with either of these primary diagnoses: E75.22 Gaucher disease or G10 Huntington’s disease.

Prior authorization is required for all other primary diagnoses.

These services require prior authorization:

CPT Copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association

Products

This information is for most, but not all, HealthPartners plans. Please read your plan documents to see if your plan has limits or will not cover some items. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage. These coverage criteria may not apply to Medicare Products if Medicare requires different coverage. For more information regarding Medicare coverage criteria or for a copy of a Medicare coverage policy, contact Member Services at 952-883-7979 or 1-800-233-9645.

Number P005-03; Approved Medical Director Committee 10/18/10; Revised 4/28/11, 2/23/12, 5/11/15, 3/8/16, 10/27/16, 2/1/17, 2/12/18, 7/19/18; Annual Review 4/2011, 2/2012, 2/2013, 2/2014, 2/2015, 5/2015, 2/2016, 2/2017, 2/2018

References

1. Altar, C. A., Carhart, J., Allen, J. D., Hall-Flavin, D., Winner, J., & Dechairo, B. (2015). Clinical utility of combinatorial pharmacogenomics-guided antidepressant therapy: Evidence from three clinical studies. Molecular Neuropsychiatry, 1, 145-155.
2. Becker, M. A. (2018). Pharmacologic urate-lowering therapy and treatment of tophi in patients with gout. In: N. Dalbeth & P. L. Romain (Eds.). UpToDate. Waltham, MA: UpToDate.
3. Bird, S. J. (2017). Chronic immunomodulating therapies for myasthenia gravis. In: J. M. Shefner, I. N. Targoff, & A. F. Eichler (Eds.). UpToDate. Waltham, MA: UpToDate.
4. Brennan, F. X., Gardner, K. R., Lombard, J., Perlis, R. H., Fava, M., Harris, H. W., & Scott, R. (2015). A naturalistic study of the effectiveness of pharmacogenetic testing to guide treatment in psychiatric patients with mood and anxiety disorders. The Primary Care Companion for CNS Disorders, 17, doi: 10.4088/PCC.14m0171
5. Clancy, J. P., Johnson, S. G., Yee, S. W., McDonagh, E. M., Caudle, K. E., Klein, T. E., . . . Clinical Pharmacogenetics Implementation Consortium. (2014). Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype. Clinical Pharmacology and Therapeutics, 95, 592-597.
6. Deenen, M. J., Meulendijks, D., Cats, A., Sechterberger, M. L., Severens, J. L., Boot, H., . . . Schellens, J. H. (2016). Upfront genotyping of DPYD*2A to individualize fluoropyrimidine therapy: A safety and cost analysis. Journal of Clinical Oncology, 34, 227-234.
7. Domchek, S. M., Aghajanian, C., Shapira-Frommer, R., Schmutzler, R. K., Audeh, M. W., Friedlander, M., . . . Kaufman, B. (2016). Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecologic Oncology, 140, 199-203.
8. Eaton, K. D., & Lyman, G. H. (2017). Dosing of anticancer agents in adults. In: P. J. Hesketh & S. R. Vora (Eds.). UpToDate. Waltham, MA: UpToDate.
9. ECRI Institute. (2015a). GeneSight Psychotropic Pharmacogenetic Testing (Assurex Health, Inc.) for guiding medication selection for patients with neuropsychiatric disorders. Plymouth Meeting, PA: ECRI Institute.
10. ECRI Institute. (2015b). Pharmacogenetic testing to guide treatment of behavioral and mental health disorders. Plymouth Meeting, PA: ECRI Institute.
11. ECRI Institute. (2016a). Pharmacogenetic testing to guide treatment of chronic pain. Plymouth Meeting, PA: ECRI Institute.
12. ECRI Institute. (2016b). Proove Opioid Response (Proove Biosciences, Inc.) for predicting clinical response and optimal dosing of opioid medications. Plymouth Meeting, PA: ECRI Institute.
13. ECRI Institute. (2016c). Proove Opioid Risk (Proove Biosciences, Inc.) for assessing risk of opioid misuse. Plymouth Meeting, PA: ECRI Institute.
14. ECRI Institute. (2017). LifeKit Predict (Prescient Medicine) for predicting risk of opioid dependency. Plymouth Meeting, PA: ECRI Institute.
15. ECRI Institute. (2018). FoundationFocus CDxBRCA (Foundation Medicine, Inc.) for determining eligibility for rucaparib (Rubraca) treatment for ovarian cancer. Plymouth Meeting, PA: ECRI Institute.
16. Elliott, L. S., Henderson, J. C., Neradilek, M. B., Moyer, N. A., Ashcraft, K. C., & Thirumaran, R. K. (2017). Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial. PLoS One, 12, e0170905.
17. Flockhart, D A., O’Kane, D., Williams, M. S., Watson, M. S., Flockhart, D. A., Gage, B., . . . ACMG Working Group on Pharmacogenetic Testing of CYP2C9, VKORC1 Alleles for Warfarin Use. (2008). Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. Genetics in Medicine, 10, 139-150.
18. Gage, B. F., Bass, A. R., Lin, H., Woller, S. C., Stevens, S. M., Al-Hammadi, N., . . . Eby, C. S. (2017). Effect of genotype-guided warfarin dosing on clinical events and anticoagulation control among patients undergoing hip or knee arthroplasty: The GIFT randomized clinical trial. JAMA, 318, 1115-1124.
19. Hardinger, K., & Magee, C. C. (2017). Pharmacology of cyclosporins and tacrolimus. In: D. E. Furst, D. C. Brennan, & A. Q. Lam (Eds.). UpToDate. Waltham, MA: UpToDate.
20. Hayes, Inc. (2015a). Comprehensive Personalized Medicine Panel. Philadelphia, PA: Hayes, Inc.
21. Hayes, Inc. (2015b). CYP3A4 Genotyping for ivacaftor metabolism and toxicity. Philadelphia, PA: Hayes, Inc.
22. Hayes, Inc. (2015c). Cytochrome P450 (CYP450) genotyping to predict responses to antidepressant and antipsychotic medications. Philadelphia, PA: Hayes, Inc.
23. Hayes, Inc. (2015d). Cytochrome P450 genotyping to predict response to opioid pain medication. Philadelphia, PA: Hayes, Inc.
24. Hayes, Inc. (2015e). STA2R SureGene Test for antipsychotic and antidepressant response. Philadelphia, PA: Hayes, Inc.
25. Hayes, Inc. (2016). SLCO1B1 pharmacogenomic genotyping for statin dosing or selection. Philadelphia, PA: Hayes, Inc.
26. Hayes, Inc. (2017a). CYP2C19 pharmacogenomic genotyping to direct clopidogrel therapy for secondary prevention in patients with a history of stroke and/or transient ischemic attack. Philadelphia, PA: Hayes, Inc.
27. Hayes, Inc. (2017b). CYP2C19 pharmacogenomic genotyping to direct clopidogrel therapy in adult patients undergoing percutaneous coronary intervention (PCI). Philadelphia, PA: Hayes, Inc.
28. Hayes, Inc. (2017c). GeneSight Psychotropic (Assurex Health Inc.). Philadelphia, PA: Hayes, Inc.
29. Hayes, Inc. (2017d). Genetic testing to predict allopurinol toxicity. Philadelphia, PA: Hayes, Inc.
30. Hayes, Inc. (2017e). MTHFR genetic testing in common clinical conditions. Philadelphia, PA: Hayes, Inc.
31. Hayes, Inc. (2017f). MTHFR pharmacogenetic genotyping for altering drug treatments. Philadelphia, PA: Hayes, Inc.
32. Hayes, Inc. (2017g). PGxOne Plus (Admera Health). Philadelphia, PA: Hayes, Inc.
33. Hayes, Inc. (2017h). Pharmacogenomic testing for selected psychiatric and behavioral conditions. Philadelphia, PA: Hayes, Inc.
34. Hirsch, M., & Birnbaum, R. J. (2018). Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. In: P. P. Roy-Byrne & D. Solomon (Eds.). UpToDate. Waltham, MA: UpToDate.
35. Holbrook, A., Schulman, S., Witt, D. M., Vandvik, P. O., Fish, J., Kovacs, M. J., . . . Guyatt, G. H. (2012). Evidence-based management of anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9^th edition: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 141, e152S-e184S.
36. Hughes, D. (2017). Gaucher disease: Treatment. In: S. Hahn & E. TePas (Eds.). UpToDate. Waltham, MA: UpToDate.
37. Hull, R. D., Garcia, D. A., & Vazquez, S. R. (2018). Warfarin and other VKAs: Dosing and adverse effects. In: L. L. K. Leung & J. S. Timauer (Eds.). UpToDate. Waltham, MA: UpToDate.
38. Jung, J. W., Kim, D. K., Park, H. W., Oh, K. H., Joo, K. W., Kim, Y. S., . . . Kang, H. R. (2015). An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing. Genetics in Medicine, 17, 807-814.
39. Kato, M., Serretti, A., Nonen, S., Takekita, Y., Wakeno, M., Azuma, J., & Kinoshita, T. (2015). Genetic variants in combination with early partial improvement as a clinical utility predictor of treatment outcome in major depressive disorder. Translational Psychiatry, 5, e513.
40. Kaufman, B., Shapira-Frommer, R., Schmutzler, R. K., Audeh, M. W., Friedlander, M., Balmana, J., . . . Domchek, S. M. (2015). Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. Journal of Clinical Oncology, 33, 244-250.
41. Khanna, D., Fitzgerald, J. D., Khanna, P. P., Bae, S., Singh, M. K., Neogi, T., . . . American College of Rheumatology. (2012). 2012 American College of Rheumatology guidelines for management of gout part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care and Research, 64, 1431-1446.
42. Krishnamurthi, S. S. (2017). Enterotoxicity of chemotherapeutic agents. In: R. E. Drews & D. M. F. Savarese (Eds.). UpToDate. Waltham, MA: UpToDate.
43. MacDermott, R. P. (2017). 6-mercaptopurine (6-MP) metabolite monitoring and TPMT testing in patients with inflammatory bowel disease. In: P. Rutgeerts & K. M. Robson (Eds.). UpToDate. Waltham, MA: UpToDate.
44. Matulonis, U. A., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., . . . Ledermann, J. A. (2016). Olaparib maintenance therapy in patients with platinum-sensitive, relapsed serous ovarian cancer and a BRCA mutation: Overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy. Cancer, 122, 1844-1852.
45. Matulonis, U. A., Penson, R. T., Domchek, S. M., Kaufman, B., Shapira-Frommer, R., Audeh, M. W., . . . Coleman, R. L. (2016). Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: A multistudy analysis of response rates and safety. Annals of Oncology, 27, 1013-1019.
46. National Comprehensive Cancer Network. (2017a). Ovarian cancer including fallopian tube cancer and primary peritoneal cancer (version 5). Fort Washington, PA: National Comprehensive Cancer Network.
47. National Comprehensive Cancer Network. (2017b). Rectal cancer (version 4). Fort Washington, PA: National Comprehensive Cancer Network.
48. National Comprehensive Cancer Network. (2018). Colon cancer (version 1). Fort Washington, PA: National Comprehensive Cancer Network.
49. Pallet, N., Etienne, I., Buchler, M., Bailly, E., Hurault de Ligny, B., Choukroun, G., . . . Thervet, E. (2016). Long-term clinical impact of adaptation of initial tacrolimus dosing to CYP3A5 genotype. American Journal of Transplantation, 16, 2670-2675.
50. Phillips, E. J., & Mallal, S. A. (2017). Abacavir hypersensitivity reaction. In: J. G. Bartlett & J. MItty (Eds.). UpToDate. Waltham, MA: UpToDate.
51. Ramsey, L. B., Johnson, S. G., Caudle, K. E., Haidar, C. E., Voora, D., Wilke, R. A., . . . Niemi, M. (2014). The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clinical Pharmacology and Therapeutics, 96, 423-428.
52. Robson, M., Im, S. A., Senkus, E., Xu, B., Domchek, S. M., Masuda, N., . . . Conte, P. (2017). Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. New England Journal of Medicine, 377, 523-533.
53. Rosenson, R. S. (2018). Mechanisms of benefit of lipid-lowering drugs in patients with coronary heart disease. In: M. W. Freeman & G. M. Saperia (Eds.). UpToDate. Waltham, MA: UpToDate.
54. Schachter, S. C. (2018). Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects. In: P. Garcia & J. F. Dashe (Eds.). UpToDate. Waltham, MA: UpToDate.
55. Shi, Y. W., Min, F. L., Zhou, D., Qin, B., Wang, J., Hu, F. Y., . . . Liao, W. P. (2017). HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions. Neurology, 88, 2183-2191.
56. Simon, R. H. (2017). Cystic fibrosis: Overview of the treatment of lung disease. In: G. B. Mallory & A. G. Hoppin (Eds.). UpToDate. Waltham, MA: UpToDate.
57. Swisher, E. M., Lin, K. K., Oza, A. M., Scott, C. L., Giordano, H., Sun, J., . . . McNeish, I. A. (2018). Rucabarib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): An international, multicenter, open-label, phase 3 trial. The Lancet Oncology, 18, I75-87.
58. Tantry, U. S., Hennekens, C. H., Zehnder, J. L., & Gurbel, P. A. (2018). Clopidogrel resistance and clopidogrel treatment failure. In: L. L.
59. Van der Weide, K., & van der Weide, J. (2015). The influence of the CYP3A4*22 and CYP2D6 polymorphisms on serum concentrations of aripiprazole, haloperidol, pimozide, and risperidone in psychiatric patients. Journal of Clinical Psychopharmacology, 35, 228-236.
60. Wang, B., Canestaro, W. J., & Choudhry, N. K. (2014). Clinical evidence supporting pharmacogenomic biomarker testing provided in US Food and Drug Administration drug labels. JAMA Internal Medicine, 174, 1938-1944.
61. Wang, Y., Zhao, X., Lin, J., Li, H., Johnston, S. C., Lin, Y., . . . CHANCE Investigators. (2016). Association between CYP2C19 loss-of-function allele status and efficacy of clopidogrel for risk reduction among patients with minor stroke or transient ischemic attack. JAMA, 316, 70-78.
62. Wright, A. A., Bohlke, K., Armstrong, D. K., Bookman, M. A., Cliby, W. A., Coleman, R. L., . . . Edelson, M. I. (2016). Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology clinical practice guideline. Gynecologic Oncology, 143, 3-15.