Documenting Pharmacogenomic Testing with CPT Codes

By Erik Hefti, PharmD, MS, and Javier G. Blanco, ClinBiochem, PhD

The “personalized medicine” paradigm is at the forefront of discussions about the future of healthcare, and a wealth of new data concerning how human genetic variation contributes to drug response has the potential to change the practice of medicine. The promise of treating patients based on their individual characteristics, rather than by using empirical and generalized guidelines alone, holds interest for many stakeholders in the healthcare and scientific communities.

The individualization of drug therapy by using a patient’s unique genetic thumbprint has already been implemented into practice. As such, the pharmaceutical industry is developing a growing repository of new drugs that are effective in specific subsets of patients carrying distinctive molecular signatures. Pharmacogenomics, which is the study of how genetics impacts drug response, aims to develop patient-specific strategies for drug therapy by combining concepts from various disciplines, including:1

  • Pharmacology
  • Pharmacokinetics
  • Drug metabolism
  • Genetics
  • Pathology
  • Pharmacodynamics

Pharmacogenetic tests allow clinicians to better predict the potential efficacy or toxicity of a drug in a particular patient. These tests can detect the presence of a specific genetic variant in a patient’s DNA, a particular mutation in tumor DNA, combinations of mRNA transcripts in tumor samples, or the expression of specific proteins in tissue specimens. All of the aforementioned factors have the potential to impact drug therapy. Pharmacogenomic testing can be performed before or during therapy, and in some cases it allows for more precise treatments of diseases, such as certain types of cancer or infection with the human immunodeficiency virus (HIV).2 Widespread implementation of clinically useful pharmacogenetic tests can save healthcare dollars by guiding clinicians toward drug regimens that have a lower likelihood of failure or toxicity.3,4 These tests can also assist clinicians with making treatment decisions, such as when to use cytotoxic chemotherapy versus hormonal therapy for the treatment of certain forms of breast cancer.5

As pharmacogenetic tests become more widely available and less expensive due to technological advances, it is reasonable to suspect that the utilization of these tests will increase.6 As this occurs, it will become more critical for health information professionals to recognize and understand the pharmacogenomic tests that are available, and how to document their usage properly. Until relatively recently, it has been difficult to document specific pharmacogenomic tests using current procedural terminology (CPT) codes. The purpose of the concise review in this article is two-fold. Past and present difficulties with documenting these tests will be presented and discussed. Select examples of currently available pharmacogenomic tests and their corresponding CPT codes will also be addressed. For this review, published reports on pharmacogenomic testing from the PubMed and OVID Medline databases were utilized. This review aims to provide health information management (HIM) professionals with a better understanding and perspective of pharmacogenomic testing that will allow for better, more accurate documentation for the purposes of billing and record keeping.

Examples of Pharmacogenomic Tests with Associated CPT Codes for Identification and Documentation

CPT Code


Description of Test


CYP2C19 genotyping

Detects genetic variants of CYP2C19 associated with variable drug metabolism


CYP2D6 genotyping

Detects genetic variants of CYP2D6 associated with variable drug metabolism


CYP2C9 genotyping

Detects genetic variants of CYP2C9 associated with variable drug metabolism


VKORC1 testing

Detects genetic variants of VKORC1 associated with warfarin therapy


UGT1A1 genotyping

Detects genetic variants of UGT1A1 associated with irinotecan toxicity


11-dehydro thromboxane B2

Measures 11-dehydro thromboxane B2 in urine to determine aspirin resistance


HLA B*57:01

Detects the HLA B*57:01 allele associated with abacavir toxicity


G6PD quantitative

Measures glucose-6-phosphate dehydrogenase activity


BRAF mutation testing

Detects mutations in BRAF associated with BRAF inhibitor therapy


KRAS mutation testing

Detects mutations in KRAS associated with KRAS inhibitor therapy


HER2 expression

Detects the expression of HER2 to guide therapy with HER2 inhibitors


EGFR mutation testing

Detects mutations in EGFR associated with EGFR inhibitor therapy


CFTR profile

Detects mutations in CFTR, which is necessary prior to therapy with ivacaftor


HIV-1 tropism testing

Determines HIV tropism for C-C chemokine receptor 5 [CCR5], and/or CX-C chemokine receptor 4 [CXCR4] to guide therapy with receptor antagonists


MGMT gene methylation

Determines MGMT methylation status to guide therapy with certain alkylating agents

Note: Some tests may be components of multi-test panels offered by various companies.

Coding Early Pharmacogenomic Testing Presented Difficulties

Pharmacogenomic testing in the clinical setting has only been available since the early to mid-2000s, with the first test approved by the US Food and Drug Administration (FDA) occurring in 2005.7 Early adopters had difficulty documenting such procedures using CPT codes for two key reasons:

  1. Lack of familiarity with the new tests
  2. Non-specific coding practices

It is not known precisely how often these tests were utilized after they debuted, but it is reasonable to suspect that they were not widely employed by practitioners. Surveys published in 2009 showed slow adoption of pharmacogenomic tests in Europe, Australia, and New Zealand.8 There were scant clinical outcomes data to justify their cost, and much of the healthcare community was likely unaware of these tests when they first debuted.9 It should be noted that to the best of our knowledge, comprehensive rates of pharmacogenomic testing in the United States have not been reported.

Early on, there were few resources available for those in HIM to consult when documenting these tests. It was also difficult to accurately and appropriately document the tests due to a lack of specific CPT codes, as the American Medical Association (AMA) considered them “molecular pathology procedures.”10 Prior to 2012, pharmacogenomic tests were often documented as such, which had many consequences. First, individual pharmacogenomic tests could not be documented efficiently or accurately, and were often loosely differentiated by “stacking” various codes for specific tests. This lack of specificity made it very difficult to have a universally accepted method for coding specific pharmacogenetic tests. Non-specific coding also made tracking the utilization trends and the cost-efficacy of these tests outside of clinical trials more difficult. Next, correct and accurate reimbursement for using these tests would be in jeopardy because of the non-specific manner in which the tests were documented.

When the first pharmacogenetic tests became available, they were rarely covered by any insurance plans, and the cost was often paid by the patients themselves. However, as more clinical studies showed the benefits that pharmacogenomic testing can offer to patients in specific circumstances, many insurance entities began to cover select tests.11 This necessitated improved documentation practices for billing, reimbursement, and recordkeeping purposes. The lack of specific procedural codes led to confusion and consternation between clinicians and health information professionals alike.

Some Unique CPT Codes Now Available

The AMA acted on requests to assign many of these pharmacogenomic tests unique CPT codes for documentation purposes in 2012.12 These CPT codes are for pharmacogenomic tests that detect specific gene variants known to impact drug therapy. The new codes went into effect in 2013. The table above shows select pharmacogenomic tests that have unique CPT codes available for documentation purposes, as well as a brief description of the test. It is important to note that additional pharmacogenomic tests are available, but many have not been assigned a specific CPT code.

Some pharmacogenomic tests are actually comprised of multiple individual tests that are performed and analyzed with a proprietary algorithm to assist in therapeutic decision making. An example of this includes multi-gene combinatorial pharmacogenomic testing for the purposes of guiding treatment of depression or breast cancer. A few healthcare management entities have even opted to cover expensive genomic testing packages which utilize multiple pharmacogenomic tests to guide therapy for specific patient populations.13 These pharmacogenetic test packages often need to be documented with multiple CPT codes as each code documents a separate test that is performed as part of the complete package. The results of the individual tests are generally used in proprietary algorithms to generate treatment recommendations for practitioners.14

More Work Needed to Address Challenges

Pharmacogenetic testing continues to pose challenges for health information professionals. Documenting the use of pharmacogenetic tests accurately can still be difficult since new tests may not have unique CPT codes available yet. Genomic services and pharmacogenetic test packages can further complicate the documentation process because a single CPT code is not available—instead multiple codes need to be used. This challenge is likely to persist as it is probable that future drugs may require new genomic tests to be developed and introduced for ensured safety. To overcome the documentation challenges posed by pharmacogenomic testing, it is important to know that many pharmacogenomic tests do have specific codes available. It is also important to stay up-to-date with annual CPT code changes involving pharmacogenomic testing in general.

The AMA does address concerns with documenting pharmacogenomic testing via CPT codes sporadically, with the revisions in 2012 being one of the largest overhauls seen yet. It may be a good option to contact those companies that offer pharmacogenomic test packages that are based on multiple “sub-tests” to inquire what specific CPT codes are appropriate for documentation. These companies are often intimately familiar with the exact codes necessary to document for proper recordkeeping and reimbursement purposes.

Currently, there is very little published research concerning the impact of the increased specificity in coding on the efficiency of documentation. In general, the topic of pharmacogenomic test documentation is relatively unexplored. The lack of research in this area leads to difficulty when attempting to validate the impact of any procedural code changes with respect to pharmacogenomics testing. As personalized medicine receives more attention from the healthcare community, it is likely that pharmacogenetic testing will become more prevalent. Being a relatively new approach to delivering optimal and individualized patient care, pharmacogenomics is still not well understood by many in healthcare.15 Its potential to improve the lives and healthcare outcomes of patients makes the understanding of pharmacogenetic tests critical. Proper documentation of pharmacogenetic testing is of great importance to health information professionals and will continue to be for the foreseeable future.


  1. Kitzmiller, Joseph et al. “Pharmacogenomic testing: Relevance in medical practice—Why drugs work in some patients but not in others.” Cleveland Clinic Journal of Medicine 78 no. 4 (April 2011): 243-257.
  2. Wang, Liewei, Howard L. McLeod, and Richard M. Weinshilboum. “Genomics and Drug Response.” New England Journal of Medicine 364, no. 12 (March 24, 2011): 1144-1153.
  3. Ventola, C. L. “Pharmacogenomics in clinical practice: Reality and expectations.” Pharmacology and Therapeutics 36, no. 7 (2011): 412-450.
  4. Winner, J. et al. “Psychiatric pharmacogenomics predicts health resource utilization of outpatients with anxiety and depression.” Translational Psychiatry 3 (2013).
  5. Carlson, J. J. and J. A. Roth. “The impact of the oncotype Dx breast cancer assay in clinical practice: A systematic review and meta-analysis.” Breast Cancer Research and Treatment 141, no. 1 (2013): 13-22.
  6. Frueh, F. W. “Real-world clinical effectiveness, regulatory transparency and payer coverage: Three ingredients for translating pharmacogenomics into clinical practice.” Pharmacogenomics 11, no. 5 (May 2010): 657-660.
  7. Ventola, C.L. “Pharmacogenomics in clinical practice: Reality and expectations.”
  8. Sheffield, Leslie J. and Hazel E. Phillimore. “Clinical Use of Pharmacogenomic Tests in 2009.” The Clinical Biochemist Reviews 30, no. 2 (2009): 55-65.
  9. McKinnon, R. A., M. B. Ward, and M. J. Sorich. “A critical analysis of barriers to the clinical implementation of pharmacogenomics.” Journal of Therapeutics and Clinical Risk Management 3, no. 5 (2007): 751-759.
  10. Wu, Alan H. B., and Kiang-Teck J. Yeo, eds. Pharmacogenomic Testing in Current Clinical Practice Implementation in the Clinical Laboratory. New York: Humana Press, 2011.
  11. Hresko, Andrew and Susanne B. Haga. “Insurance Coverage Policies for Personalized Medicine.” Journal of Personalized Medicine 2, no. 4 (October 30, 2012): 201-216.
  12. Ohara, Karen. “CPT Code Updates for 2012.” Journal of AHIMA website. January 27, 2012.
  13. Assurex Health. “U.S. Department of Veterans Affairs Awards GeneSight® Federal Supply Schedule Contract.” Press release. June 24, 2014.
  14. Hall-Flavin, D. K. et al. “Using a pharmacogenomic algorithm to guide the treatment of depression.” Translational Psychiatry 2, no. 10 (2012): e172.
  15. Mrazek, D. A. and C. Lerman. “Facilitating clinical implementation of pharmacogenomics.” Journal of the American Medical Association 306, no. 3 (July 20, 2011): 304-305.

Erik Hefti ( is a PhD candidate and Javier G. Blanco is an associate professor in the department of pharmaceutical sciences at the State University of New York at Buffalo.

Article citation:
Hefti, Erik ; Blanco, Javier G. "Documenting Pharmacogenomic Testing with CPT Codes" Journal of AHIMA 87, no.1 (January 2016): 56-59.