Grant Summary: Risk-benefit trade-offs for whole genome sequencing

The major goals of this project were to evaluate the potential benefit-risk tradeoffs of whole genome sequencing (WGS) from the perspectives of patients, providers, the health care delivery system, and society by using systematic and quantitative approaches. Our specific aims were to examine patient preferences, coverage and reimbursement decisions, and economic value.

In total, we published 31 papers, including key articles in influential journals such as JAMA, Science, Health Affairs, Genetics in Medicine, Nature Biotechnology, and Journal of the National Comprehensive Cancer Network.


We completed a survey from a nationally representative sample of 410 respondents on willingness-to-pay and also included a discrete choice experiment to measure how patients make trade-offs. The results of this survey resulted in the publication of 2 articles, one on the analysis of willingness-to-pay, and a second using the discrete choice experiment data. We also published a paper with MedSeq collaborators to publish a paper on willingness-to-pay using data from MedSeq and a survey of college seniors.


We analyzed coverage policies and conducted interviews with clinical experts and payers, resulting in the completion of three papers for panels including BRCA, for inherited cancer risk panels, and for tumor sequencing. We also examined how to engage public payers and smaller regional payers in order to expand our work beyond the large private payers.

In the final year and NCE, we analyzed coverage policies and conducted interviews with clinical experts and payers, resulting in the completion of 8 papers and several presentations and posters on coverage policies (for panels including BRCA, inherited cancer risk panels, tumor sequencing, cell-free DNA prenatal screening, and whole exome sequencing).

We also evaluated historical insurer coverage frameworks for Next-Generation Sequencing as part of a Value in Health theme issued published in 2018.

Last, we had a series of publications in Science, JAMA, and Journal of Clinical Oncology Precision Oncology regarding the coverage of Next-Generation Tumor Sequencing by the Centers for Medicaid and Medicare (CMS) National Coverage Decision.


We published a paper on the budget impact and true costs of sequencing (Is the “$1000 Genome” Really $1000?). We published a paper on how to assess the true costs of sequencing and a second paper in Genetics in Medicine on what is known about the cost-effectiveness of clinically actionable incidental findings.

In the final year and NCE, we published 12 papers related to the Economics or Value of Sequencing and contributed to a book chapter on the evaluation and evidence of personalized medicine. These publications include a paper on budget impact and true costs of sequencing, several reviewing the economic evidence, methodological challenges and solutions for assessment of NGS tests, and 2 with MedSeq Collaborators on the short-term costs of WGS and lessons learned form cost analyses of WGS.

Additionally, we obtained a supplement (3R01HG007063-02S1) – “Who is Paying, Will be Paying, and Should be Paying for Genomic Sequencing?” This supplement addressed the overall objective of the parent R01 – to examine benefit-risk tradeoffs for sequencing. We focused on reimbursement issues by developing a comprehensive registry of public and private payer coverage policies for new and emerging sequencing tests, as well as illustrative examples of existing molecular diagnostic (MDx) tests for comparative analyses. The outcome of creating this registry and subsequent analyses resulted in 6 publications. The registry is currently being used for additional NIH-sponsored research.

Publications stemming from this grant include:

  1. Phillips, KA; Sakowski JA; Trosman, J; Douglas, MP; Liang S; and Neumann, P. The Economic Value of Personalized Medicine: What We Know and What We Need to Know. Genet Med. 2014. Mar;16(3):251-7. (PMCID: PMC3949119)
  2. Phillips, K. A., J. R. Trosman, R. K. Kelley, M. J. Pletcher, M. P. Douglas and C. B. Weldon Genomic sequencing: assessing the health care system, policy, and big-data implications. Health Affairs. 2014. 33(7): 1246-1253. (PMCID: PMC4113721)
  3. Phillips, KA; and Labno A. Private Companies Providing Health Care Price Data: Who Are They and What Information do They Provide? 2014. JMCM. 17(4):75-80. (PMCID: PMC4323083)
  4. Garfield S, Douglas MP, MacDonald KV, Marshall DA, and Phillips K A. Consumer familiarity, perspectives, and expected value of personalized medicine with a focus on applications in oncology. Personalized Medicine. 2015. 12(1):13-22 (PMCID: PMC4303575)
  5. Clain E, Trosman JR, Douglas MP, Weldon CB, and Phillips KA. Availability and payer coverage of BRCA1/2 tests and gene panels. Nat Biotechnol. 2015. 33(9):900-2. (PMCID: PMC4625918)
  6. Douglas MP, Ladabaum U, Pletcher MJ, Marshall DA, Phillips KA. Economic evidence on identifying clinically actionable findings with whole-genome sequencing: a scoping review. Genet Med. 2016 Feb;18(2):111-6. (PMCID: PMC4654986)
  7. Phillips KA, Ladabaum U, Pletcher MJ, Marshall DA, Douglas MP. Key emerging themes for assessing the cost-effectiveness of reporting incidental findings. Genet Med. 2015. 17(4):314-5. (PMCID: PMC4395812)
  8. Trosman JR, Weldon CB, Kelley RK, Phillips KA. Challenges of coverage policy development for next-generation tumor sequencing panels: Experts and Payers Weigh in. JNCCN. 2015. 13(3):311-8. (PMCID: PMC4372087)
  9. Phillips KA, Pletcher MJ, Ladabaum U. Is the “$1000 Genome” Really $1000? Understanding the Full Benefits and Costs of Genomic Sequencing. Technol Health Care 2015. 23(3)373-379. (PMCID: PMC4527943)
  10. Payne K, Redekop K, and Phillips KA. (2016) Personalized Medicine: Economic Evaluation and Evidence (book chapter). In World Scientific Handbook of Global Health Economics and Public Policy, Vol. 2, edited by Richard M. Scheffler. World Scientific, Imperial College Press. Hackensack, NJ.
  11. Phillips KA, Schleifer D, Hagelskamp C. Most Americans Do Not Believe That There Is An Association Between Health Care Prices And Quality Of Care. Health Affairs. 2016, 35:647-653. (PMCID: PMC5029784)
  12. Marshall DA, Gonzalez JM, Johnson FR, MacDonald KV, Pugh A, Douglas MP, Phillips KA. Who decides and what are people willing-to-pay for whole genome sequencing information? Genet Med. 2016; Dec;18(12):1295-1302. (PMCID: PMC5133139)
  13. Trosman JR, Weldon CB, Douglas MP, Kurian AW, Kelley RK, Deverka PA, Phillips KA. Payer Coverage for Hereditary Cancer Panels: Barriers, Opportunities, and Implications for the Precision Medicine Initiative. J Natl Compr Canc Netw. 2017; Feb;15(2):219-228. (PMCID: PMC5508568)
  14. Dervan AP, Deverka PA, Trosman JR, Weldon CB, Douglas MP, and Phillips KA. Payer Decision-Making for Next Generation Sequencing-Based Genetic Tests: Insights from Cell-Free DNA Prenatal Screening. Genet Med, 2017; May;19(5):559-567. (PMCID: PMC5362360)
  15. Marshall DA, Gonzalez JM, MacDonald KV, et al. Estimating Preferences for Complex Health Technologies: Lessons Learned and Implications for Personalized Medicine. Value Health. 2017;20(1): 32-39. (PMCID: PMC5319756)
  16. Phillips KA, Douglas MP, Trosman JR, et al. "What Goes Around Comes Around": Lessons Learned from Economic Evaluations of Personalized Medicine Applied to Digital Medicine. Value Health. 2017;20(1): 47-53. (PMCID: PMC5319740)
  17. Trosman JR, Weldon CB, Douglas MP, et al. Decision-Making on Medical Innovations in a Changing Health Environment: Insights from Accountable Care Organizations and Payers on Personalized Medicine and Other Technologies. Value Health. 2017;20(1): 40-46. (PMCID: PMC5319741)
  18. Marshall DA, MacDonald KV, Oliver Robinson J, Barcellos LF, Gianfrancesco M, Helm M, McGuire A, Green RC, Douglas MP, Goldman MA, Phillips KA. The price of whole genome sequencing may be decreasing, but who will be sequenced? Personalized Medicine, 2017; 14(2): 203-211. (PMCID: PMC5629976)
  19. Phillips KA, Deverka PA, Sox HC, Khoury MJ, Sandy LG, Ginsburg GS, Tunis SR, Orlando LA, Douglas MP. Making genomic medicine evidence-based and patient-centered: a structured review and landscape analysis of comparative effectiveness research. Genet Med. 2017; 19:1081-1091. (PMCID: PMC5629101)
  20. Phillips KA, Deverka PA, Trosman JR, Douglas MP, Chambers JD, Weldon CB, Dervan AP. Payer coverage policies for multigene tests. Nat Biotechnol. 2017 Jul 12;35(7):614-617. (PMCID: PMC5553867)
  21. Chambers JD, Saret CJ, Anderson JA, Deverka PA, Douglas MP, Phillips KA. Examining payer coverage policies for multi-gene panels and sequencing technology. Int J Technol Assess Health Care. 2017 Oct 25:1-7. (PMCID: PMC5732073)
  22. Phillips KA, Deverka PA, Hooker GW, Douglas MP. Genetic Test Availability And Spending: Where Are We Now? Where Are We Going? Health Aff (Millwood). 2018;37(5):710-716. (PMCID: PMC5987210)
  23. Ginsburg GS, Phillips KA. Precision Medicine: From Science to Value. Health Aff (Millwood). 2018;37(5):694-701. (PMCID: PMC5989714)
  24. Christensen KD, Vassy JL, Phillips KA, Blout CL, Azzariti DR, Lu CY, Robinson JO, Lee K, Douglas MP, Yeh JM, Machini K, Stout NK, Rehm HL, McGuire AL, Green RC, Dukhovny D. Short-term costs of integrating whole-genome sequencing into primary care and cardiology settings: a pilot randomized trial. Genet Med. 2018 Mar 22 (PMCID: PMC6151171 )
  25. Douglas MP, Parker SL, Trosman JR, Slavotinek AM, Phillips KA. Private Payer Coverage Policies for Whole Exome Sequencing (WES) in Pediatric Patients: Trends Over Time and Analysis of Evidence Cited. Genet. Med. 2018; Jul 12. [Epub ahead of print]. (PMCID: PMC6329652)
  26. Phillips KA, Trosman JR, Deverka PA, Quinn B, Tunis S, Neumann PJ, Chambers JD, Garrison LP Jr., Douglas MP, Weldon CB. Insurance coverage for genomic tests. Science. 2018; 360(6386):278-279. (PMCID: PMC5991085)
  27. Phillips KA. Evolving Payer Coverage Policies on Genomic Sequencing Tests: Beginning of the End or End of the Beginning? JAMA. 2018; 319(23):2379-2380. (PMCID: PMC6013401)
  28. Phillips KA, Deverka PA, Marshall DA, Wordsworth S, Regier DA, Christensen KD, Buchanan J. Methodological Challenges and Solutions for Assessing Economic Value of Next Generation Sequencing Tests. Value Health. 2018; 21(9):1033-1042. (PMCID: PMC6159915)
  29. Trosman JR, Weldon CB, Gradishar WJ, Benson AB III, Cristofanilli M, Kurian AW, Ford JM, Balch A, Watkins J, Phillips KA. From the Past to the Present: Insurer Coverage Frameworks for Next-Generation Tumor Sequencing. Value Health. 2018; 21(9):1062-1068. (PMCID: PMC6374027)
  30. Phillips KA, Trosman JR, Weldon CB, Douglas MP. The New Medicare Coverage Policy for Next Generation Tumor Sequencing: A Key Shift in Coverage Criteria with Broad Implications beyond Medicare. JCO Precis Oncol. 2018 :2, 1-5. (PMCID: PMC6503521)
  31. Christensen KD, Phillips KA, Green RC, Dukhovny D. Cost Analyses of Genomic Sequencing – Lessons Learned from the MedSeq Project. Value Health. Value Health. 2018; 21(9):1054-1061. (PMCID: PMC6444358)