Clinical integration of next generation sequencing: Coverage and reimbursement challenges

Journal of Law, Medicine and Ethics

Volumn 42, Issue s1, 2014, Pages 22-41

  Deverka, Patricia A ^a   Dreyfus, Jennifer C ^b  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

^b LLC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA SEQUENCE; ECONOMICS; HEALTH INSURANCE; HIGH THROUGHPUT SEQUENCING; HUMAN; HUMAN GENOME; INSURANCE; MEDICAL TECHNOLOGY; PERSONALIZED MEDICINE; REIMBURSEMENT; UNITED STATES;

GENOME, HUMAN; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; INSURANCE COVERAGE; INSURANCE, HEALTH; MEDICAL LABORATORY SCIENCE; PRECISION MEDICINE; REIMBURSEMENT MECHANISMS; SEQUENCE ANALYSIS, DNA; UNITED STATES;

EID: 84907875064     PISSN: 10731105     EISSN: 1748720X     Source Type: Journal    
DOI: 10.1111/jlme.12160     Document Type: Article

References (96)

1. C. B. Mauer, S. M. Pirzadeh-Miller, L. S. Robinson et al., "The Integration of Next-Generation Sequencing Panels in the Clinical Cancer Genetics Practice: An Institutional Experience, " Genetics in Medicine 16, no. 5 (2013): 407-412
2. F. E Dewey, M. E. Grove, and C. Pan et al., "Clinical Interpretation and Implications of Whole-Genome Sequencing, " JAMA 311, no. 10 (2014): 1035-1044.
3. P. Deverka, T. Doksum, and R. Carlson, "Integrating Molecular Medicine into the US Health-Care System: Opportunities, Barriers, and Policy Challenges, " Clinical Pharmacology and. Therapeutics 82, no. 4 (2007): 427-434.
4. C. Wilson, S. Schulz, and S. Waldman, "Biomarker Development, Commercialization, and Regulation: Individualization of Medicine Lost in Translation, " Clinical Pharmacology and Therapeutics 81, no. 2 (2007): 153-155
5. W. H. Rogowski, S. D. Grosse, and M. J. Khoury, "Challenges of Translating Genetic Tests into Clinical and Public Health Practice, " Nature Reviews Genetics 10, no 7. (2009): 489-495.
6. UnitedHealth Center for Health Reform & Modernization, Personalized Medicine: Trends and Prospects for the New Science of Genetic Testing and Molecular Diagnostics, Working Paper 7 (Minnetonka, Minnesota, 2012)
7. Blue Cross Blue Shield Association, Technology Evaluation Center Criteria, available at (last visited June 18, 2014).
8. J. Trosman, S. van Bebber, and K. Phillips, "Coverage Policy Development for Personalized Medicine: Private Payer Perspectives on Developing Policy for the 21-Gene Assay, " Journal of Oncology Practice 6, no. 5 (2010): 238-242; Palmetto, MolDx Technical Assessment Process, available at (last visited June 18, 2014).
9. A. Raskin and E. Casdin, The Dawn of Molecular Medicine: The Transformation of Medicine and Its Consequences for Investors: Executive Summary (New York: AllianceBernstein, 2011)
10. R. Tuckson, L. Newcomer, and J. De Sa, "Accessing Genomic Medicine: Affordability, Diffusion, and Disparities, " JAMA 309, no. 14. (2013): 1469-1470.
11. See UnitedHealth Center for Health Reform & Modernization
12. P. Deverka, "Pharmacogenomics, Evidence, and the Role of Payers, " Public Health Genomics 12, no. 3 (2009): 149-157.
13. A. M. Garber, "Evidence-Based Coverage Policy, " Health Affairs 20, no. 5 (2001): 62-82; Aetna, "Utilization Management: Guidelines for Determining Coverage, " available at (last visited June 18, 2014)
14. UnitedHealth Center for Health Reform & Modernization
15. M. Williams, "Insurance Coverage for Pharmacogenomics Testing in the USA, " Personalized Medicine 4, no. 4 (2007): 479-487.
16. I. Schrijver, N. Aziz, and D. H. Farkas et al., "Opportunities and Challenges Associated with Clinical Diagnostic Genome Sequencing: A Report of the Association for Molecular Pathology, " Journal of Molecular Diagnostics 14, no. 6 (2012): 525-540
17. Blue Cross Blue Shield Association
18. See UnitedHealth Center for Health Reform & Modernization,
19. F. Sun, W. Bruening, and S. Uhl, et al., Technology Assessment: Quality, Regulation and Clinical Utility of Laboratory-Developed Molecular Tests, Corrected Version (Agency for Healthcare Research and Quality Technology Assessment Program, 2010).
20. F. S. Collins and M. A. Hamburg, "First FDA Authorization for Next-Generation Sequencer, " New England Journal of Medicine 369, no. 25 (2013): 2369-2371.
21. A. Paxton, CAP Today, "CAP Leads Way with Next-Gen Checklist, " August 2012, available at (last visited June 18, 2014).
22. H. L. Rehm, S. J. Bale, and P. Bayrak-Toydemir et al., "ACMG Clinical Laboratory Standards for Next-generation Sequencing, " Genetics in Medicine 15, no. 9 (2013): 733-747.
23. A. S. Gargis, L. Kalman, and M. W. Berry et al., "Assuring the Quality of Next-Generation Sequencing in Clinical Laboratory Practice, " Nature Biotechnology 30, no. 11 (2012): 1033-1036.
24. S. Kamalakaran, V. Varadan, and A. Janevski et al., "Translating Next Generation Sequencing to Practice: Opportunities and Necessary Steps, " Molecular Oncology 7, no. 4 (2013): 743-755.
25. F. S. Ong, J. C. Lin, and K. Das et al., "Translational Utility of Next-Generation Sequencing, " Genomics 102, no. 3 (2013): 137-139.
26. S. H. Katsanis and N. Katsanis, "Molecular Genetic Testing and the Future of Clinical Genomics, " Nature Reviews Genetics 14, no. 6 (2013): 415-426.
27. S. Teutsch, L. Bradley, and G. Palomaki et al., "The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative: Methods of the EGAPP Working Group, " Genetics in Medicine 11, no. 1 (2009): 3-14.
28. L. M. Meckley and P. J. Neumann, "Personalized Medicine: Factors Influencing Reimbursement, " Health Policy 94, no. 2 (2010): 91-100.
29. M. Graf, D. Needham, and N. Teed et al., "Genetic Testing Insurance Coverage Trends: A Review of Publicly Available Policies from the Largest US Payers, " Future Medicine 10, no. 3 (2013): 235-243.
30. D. Veenstra, M. Piper, and J. Haddow et al., "Improving the Efficiency and Relevance of Evidence-Based Recommendations in the Era of Whole-Genome Sequencing: An EGAPP Methods Update, " Genetics in Medicine 15, no. 1 (2013): 14-24.
31. Centers for Disease Control and Prevention, "Genomic Tests and Family History by Levels of Evidence, " available at (last visited May 9, 2013).
32. GAPPFinder, available at (last visited August 2, 2013).
33. Hayes Inc., "Genetic Test Evaluation, " available at (last visited June 18, 2014).
34. ECRI Institute, "Health Technology Assessment Information Service: Patient-Centered Outcomes Research and Evidence-based Reports for Better Health Technology Decisions, " available at (last visited June 18, 2014).
35. R. Wolf, "A CEO's Guide to Molecular Diagnostic Reimbursement: Navigating the Many Challenges of Reimbursement and Commercialization, " DARK Daily Laboratory and Pathology News, available at (last visited June 18, 2014).
36. See Blue Cross Blue Shield Association,
37. Palmetto GBA, "Molecular Diagnostic Program (MolDXSM) Coverage, Coding, and Pricing Standards and Requirements, " available at (last visited June 18, 2014).
38. E. Lyon and R. Weiss, "The Shifting Regulatory Sands for Clinical Laboratories: The FDA and Other Things, " December 15, 2011, available at (last visited June 18, 2014)
39. C. Wintering, "The Evolving MolDX Program in Quadax, " 2012, available at (last visited June 18, 2014)
40. M. Abraham, J. T. Ahlman, and A. J. Boudreau, Current Procedural Terminology (CPT): Professional Education (American Medical Association, 2013).
41. "McKesson, AMA Developing Reference Product for MDx, " GenomeWeb Daily News, February 26, 2013, available at (last visited June 18, 2014).
42. Quorum Consulting, Diagnostics Reimbursement Quarterly 1, no. 1 (August 2012), available at (last visited June 18, 2014)
43. Xifin, "Mopath Code Fees by Payor, " available at (last visited June 18, 2014).
44. T. Ray, "CMS Issues Pricing for MDx Codes; Labs, Test Developers Still Critical of Rates and Methodology, " GenomeWeb, May 22, 2013, available at (login required; last visited May 5, 2014).
45. B. Carlson, "Seeking a Coding Solution for Molecular Tests: Managing the Estimated 1, 700 Molecular Tests Now on the Market Is Impossible without a Unique CPT Code for Each Test. What's at Stake? The Future of Personalized Medicine, " Biotechnology Healthcare 7, no. 3 (2010): 16-20.
46. See UnitedHealth Center for Health Reform & Modernization,
47. See UnitedHealth Center for Health Reform & Modernization
48. S. D. Walcoff and J. D. Pfeifer, "Modernizing US Regulatory and Reimbursement Policy to Support Continued Innovation in Genomic Pathology, " Personalized Medicine 9, no. 3 (2012): 295-308.
49. Centers for Medicare and Medicaid Services, National Coverage Determination (NCD) for Cyotgenetic Studies, available at (last visited June 23, 2014).
50. Centers for Medicare and Medicaid Services, National Coverage Determination (NCD) for Pharmacogenomic Testing for Warfarin Response (90.1), available at (last visited June 23, 2014).
51. Blue Cross Blue Shield, Special Report: Exome Sequencing for Clinical Diagnosis of Patients with Suspected Genetic Disorders, August 2013, available at (last visited June 23, 2014).
52. Genome Web, "William Blair Downgrades Sequenom, Citing Coding Issues and Increased Competition; Shares Down Sharply, " July 25, 2013, available at (last visited June 23, 2014).
53. FoundationOne, Billing and Reimbursement: Answers for Patients and Caregivers, " available at (last visited May 12, 2013).
54. Blue Cross Blue Shield Association, "Sequencing-Based Tests to Determine Fetal Down Syndrome (Trisomy 21) from Maternal Plasma DNA, " Technology Evaluation Center Assessment Program Executive Summary No. 10 (2013).
55. K. E. Ormond, M. T. Wheeler, and L. Hudgins et al., "Challenges in the Clinical Application of Whole-Genome Sequencing, " The Lancet 375, no. 9727 (2010): 1749-1751.
56. L. Biesecker, W. Burke, and I. Kohane et al., "Next-Generation Sequencing in the Clinic: Are We Ready?" Nature Reviews Genetics 13, no. 11 (2012): 818-824.
57. ACMG, American College of Medical Genetics Policy Statement: Points to Consider in the Clinical Application of Genomic Sequencing, May 15, 2012, available at (last visited June 23, 2014); ACMG, ACMG Updates Recommendation on "Opt Out" for Genome Sequencing Return of Results, Press Release, available at (last visited June 23, 2014).
58. ACMG, ACMG Updates Recommendation on "Opt Out" for Genome Sequencing Return of Results, Press Release, available at (last visited June 23, 2014).
59. L. F. Ross, M. A. Rothstein, and E. W. Clayton, "Mandatory Extended Searches in All Genome Sequencing: 'Incidental Findings, ' Patient Autonomy, and Shared Decision Making, " JAMA 310, no. 4 (2013): 367-368
60. R. C. Green, J. R. Lupski, and L. G. Biesecker, "Reporting Genomic Sequencing Results to Ordering Clinicians: Incidental, But Not Exceptional, " JAMA 310, no. 4 (2013): 365-366.
61. F. Meric-Bernstam, C. Farhangfar, and J. Mendelsohn et al., "Building a Personalized Medicine Infrastructure at a Major Cancer Center, " Journal of Clinical Oncology 31, no. 15 (2013): 1849-1857
62. S. Moorthie, A. Hall, and C. F. Wright, "Informatics and Clinical Genome Sequencing: Opening the Black Box, " Genetics in Medicine 15, no. 3 (2013): 165-171.
63. J. E. Saffitz, "Genomic Pathology: A Disruptive Innovation, " Personalized Medicine 9, no. 3 (2012): 237-239.
64. A. Berger and S. Olson, The Economics of Genomic Medicine: Workshop Summary (Institute of Medicine, Washington, D.C., 2013).
65. S. Olson, S. Beachy, C. Giammaria, and A. Berger, Integrating Large-Scale Genomic Information into Clinical Practice: Roundtable on Translating Genomic-Based Research for Health: Workshop Summary (Institute of Medicine, Washington, D.C., 2012); see Ormond et al., .
66. J. M. Crawford and M. G. Aspinall, "The Business Value and Cost-Effectiveness of Genomic Medicine, " Personalized Medicine 9, no. 3 (2012): 265-286.
67. See UnitedHealth Center for Health Reform & Modernization,
68. P. F. Engstrom, M. G. Bloom, and G. D. Demetri et al., "NCCN Molecular Testing Paper: Effectiveness, Efficiency, and Reimbursement, " Journal of the National Comprehensive Cancer Network 9, no. S6 (2011): S-1-S-16.
69. R. C. Green, J. S. Berg, and W. W. Grody et al., "ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing, " Genetics in Medicine 15, no. 7 (2013): 565-574.
70. W. Burke, A. H. M. Antommaria, and R. Bennett et al., "Recommendations for Returning Genomic Incidental Findings? We Need to Talk" Genetics in Medicine 15, no. 11 (2013): 854-859.
71. See Rehm et al., supra note 23; see ACMG (American College of Medical Genetics Policy Statement)
72. O. Gottesman, H. Kuivaniemi, and G. Tromp et al., "The Electronic Medical Records and Genomics (Emerge) Network: Past, Present, Future, " Genetics in Medicine 15, no. 10 (2013) 761-771.
73. A. J. Goldenberg and R. R. Sharp, "The Ethical Hazards and Programmatic Challenges of Genomic Newborn Screening, " JAMA 307, no. 5 (2012): 461-462.
74. U.S. Department of Health and Human Services, Discretionary Advisory Committee on Heritable Disorders in Newborns and Children, " available at (last visited March 21, 2014).
75. J. Karow, "With Up to $25M in NIH Funding, Four Pilot Projects Will Test Genome Sequencing in Newborn Screening, " Genome Web, September 4, 2013, available at (login required; last visited May 4, 2014).
76. C. Bell, D. Dinwiddie, and N. Miller et al., "Carrier Testing for Severe Childhood Recessive Diseases by Next-Generation Sequencing, " Science Translational Medicine 3, no. 65 (2011): 65ra4.
77. L. Jackson and R. E. Pyeritz, "Molecular Technologies Open New Clinical Genetic Vistas, " Science Translational Medicine 3, no. 65 (2011): 65ps2.
78. See ACMG (American College of Medical Genetics Policy Statement)
79. J. S. King, "Genetic Tests: Politics and Fetal Diagnostics Collide, " Nature 491, no. 7422 (2012): 33-34.
80. R. Rebouche and K. Rothenberg, "Mixed Messages: The Intersection of Prenatal Genetic Testing and Abortion, " Howard Law Journal 55, no. 3 (2012): 983-1023.
81. M. Heger, "Using NGS as CDx Will Require Paradigm Shift, Regulatory Changes, According to Experts at AACR, " Genome Web, April 16, 2014, available at (login required; last visited May 4, 2014).
82. See Blue Cross Blue Shield Association
83. P. Deverka, D. Messner, and T. Dutta, Effectiveness Guidance Document: Evaluation of Clinical Validity and Clinical Utility of Actionable Molecular Diagnostic Tests in Adult Oncology (Center for Medical Technology Policy, Baltimore, MD, 2013)
84. N. I. Simonds, M. J. Khoury, and S. D. Schully et al., "Comparative Effectiveness Research in Cancer Genomics and Precision Medicine: Current Landscape and Future Prospects, " Journal of the National Cancer Institute 105, no. 13 (2013): 929-936.
85. Blue Cross Blue Shield Association, "Special Report: Multiple Molecular Testing of Cancers to Identify Targeted Therapies, " Technology Evaluation Center Assessment Program Exeutive. Summary 28, no. 1 (2013).
86. G. Frampton, "Validation of a Comprehensive NGS-Based Cancer Genomic Assay for Clinical Use, " Presented at the American Association for Clinical Chemistry Annual Meeting, July 17, 2012
87. N. Duan, R. L. Kravitz, and C. H. Schmid, "Single-Patient (N-of-1) Trials: A Pragmatic Clinical Decision Methodology for Patient-Centered Comparative Effectiveness Research, " Journal of Clinical Epidemiology 66, no. S8 (2013): S21-S28
88. N. B. Gabler, N. Duan, and S. Vohra et al., "N-of-1 Trials in the Medical Literature: A Systematic Review, " Medical Care 49, no. 8 (2011): 761-768.
89. E. O. Lillie, B. Patay, and J. Diamant et al., "The N-of-1 Clinical Trial: The Ultimate Strategy for Individualizing Medicine?" Personalized Medicine 8, no. 2 (2011): 161-173.
90. National Institutes of Health, "NIH Program Explores the Use of Genomic Sequencing in Newborn Healthcare, " available at (last visited June 24, 2014).
91. J. Armstrong, "Implementing Genomic Medicine Programs: Financial Impact, " (PowerPoint presentation), May 3-4, 2012, available at (last visited March 20, 2013).
92. B. Carlson, "Payers Try New Approaches to Manage Molecular Diagnostics: Some Payers Require Prior Authorization for Molecular Diagnostic Testing and Some Don't. And Some Payers Are Looking at Other Options, " Biotechnology and Healthcare 7, no. 3 (2010): 26-30.
93. GenomeWeb, "Health Reform Covers Breast Cancer Test, " March 2013, available at (login required; last visited March 20, 2013).
94. Center for Medical Technology Policy, "Green Park Collaborative, " available at (last visited June 24, 2014).
95. Medical Device Innovation Consortium homepage, available at (last visited June 24, 2014).
96. National Biomarker Development Alliance homepage, available at (last visited May 4, 2014).