Grant Summary: Personalized Medicine for Breast and Colorectal Cancer

The objective of this P01 was to use an integrated, interdisciplinary approach to obtain evidence about key aspects of the translation of genomic information for breast and colorectal cancer into clinical practice and health policy. The Specific Aims were:

AIM 1: Determine utilization of genomic risk stratification and targeted treatment by using the examples of GEP and HER2/neu testing for trastuzumab (Herceptin®) for breast cancer.

AIM 2: Develop an understanding of preferences for genomic testing and interventions using the example of Lynch-syndrome screening.

AIM 3: Develop a generalized, flexible model for evaluating the cost-effectiveness of personalized medicine and estimate the cost-effectiveness of GEP and HER2/neu testing for trastuzumab and Lynch-syndrome screening using unique data from the Program Projects.

AIM 4: Develop an evidence base for translating research findings into practice and policy by collecting and synthesizing data on the clinical applications and the regulatory, policy, and economic impacts of genetically based colorectal and breast cancer interventions.

AIM 5: Provide Projects with resources for conceptualizing, measuring, and investigating population differences; conducting qualitative and quantitative research; identifying and obtaining data sources; coordinating activities; and disseminating findings.

Key findings across studies are:

  1. There is a lack of evidence on how personalized medicine is implemented in actual practice and thus its value in “real world” settings.
  2. It is unclear whether personalized medicine will be cost-saving or more cost-effective than other alternatives.
  3. Analyses of targeted testing need to consider the method of targeting in order to appropriately assess the value of personalized medicine.
  4. Behavior of family members is a key factor in determining the value of personalized medicine for inherited mutations.
  5. Patient and provider preferences may affect the cost-effectiveness of personalized medicine.
  6. Payers struggle with how to assess the value of personalized medicine for making coverage and reimbursement decisions.
  7. Diffusion of personalized medicine appears to lag for certain subgroups, with implications for utilization and cost-effectiveness.

This program project grant produced 57 publications including key studies in JAMA, Nature Biotechnology, Cancer, and Genetics in Medicine.

  1. Phillips, K. A. (2008). "Closing the evidence gap in the use of emerging testing technologies in clinical practice." JAMA 300(21): 2542-2544. PMCID: 2910511.
  2. Phillips, K. A., S. Liang, S. Van Bebber and CANPERS Research Group (2008). "Challenges to the translation of genomic information into clinical practice and health policy: Utilization, preferences and economic value." Curr Opin Mol Ther 10(3): 260-266. PMCID: 2910510.
  3. Parekh, M., A. M. Fendrick and U. Ladabaum (2008). "As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasia." Aliment Pharmacol Ther 27(8): 697-712. PMCID: 3170173.
  4. Payne, K., W. G. Newman, D. Gurwitz, D. Ibarreta and K. A. Phillips (2008). "TPMT testing in azathioprine: a ‘cost-effective use of healthcare resources’?" Personalized Medicine 6(1): 103-113.
  5. Afable-Munsuz, A., S. Y. Liang, N. A. Ponce and J. M. Walsh (2009). "Acculturation and colorectal cancer screening among older Latino adults: differential associations by national origin." J Gen Intern Med 24(8): 963-970. PMCID: 2710471.
  6. Ferrusi, I. L., D. A. Marshall, N. A. Kulin, N. B. Leighl and K. A. Phillips (2009). "Looking back at 10 years of trastuzumab therapy: what is the role of HER2 testing? A systematic review of health economic analyses." Per Med 6(2): 193-215. PMCID: 2910630.
  7. Ikediobi, O. N., J. Shin, R. L. Nussbaum, K. A. Phillips, J. M. Walsh, U. Ladabaum and D. Marshall (2009). "Addressing the challenges of the clinical application of pharmacogenetic testing." Clin Pharmacol Ther 86(1): 28-31. PMCID: 2910521.
  8. Liang, S. Y., J. S. Haas and K. A. Phillips (2009). "Medicare formulary coverage for top-selling biologics." Nat Biotechnol 27(12): 1082-1084. PMCID: 2845541.
  9. Marshall, D. A., F. R. Johnson, N. A. Kulin, S. Ozdemir, J. M. Walsh, J. K. Marshall, S. Van Bebber and K. A. Phillips (2009). "How do physician assessments of patient preferences for colorectal cancer screening tests differ from actual preferences? A comparison in Canada and the United States using a stated-choice survey." Health Econ 18(12): 1420-1439.
  10. Phillips, K. A., D. A. Marshall, J. S. Haas, E. B. Elkin, S. Y. Liang, M. J. Hassett, I. Ferrusi, J. E. Brock and S. L. Van Bebber (2009). "Clinical practice patterns and cost effectiveness of human epidermal growth receptor 2 testing strategies in breast cancer patients." Cancer 115(22): 5166-5174. PMCID: 2783254.
  11. Wideroff, L., K. A. Phillips, G. Randhawa, A. Ambs, K. Armstrong, C. L. Bennett, M. L. Brown, M. S. Donaldson, M. Follen, S. J. Goldie, R. A. Hiatt, M. J. Khoury, G. Lewis, H. L. McLeod, M. Piper, I. Powell, D. Schrag, K. A. Schulman and J. Scott (2009). "A health services research agenda for cellular, molecular and genomic technologies in cancer care." Public Health Genomics 12(4): 233-244. PMCID: 2844634.
  12. Harris, J., D. J. Bowen, H. Badr, P. Hannon, J. Hay and K. Regan Sterba (2009). "Family communication during the cancer experience." J Health Commun 14 Suppl 1: 76-84.
  13. Harris, J. N., D. J. Bowen, A. Kuniyuki, L. McIntosh, L. M. FitzGerald, E. A. Ostrander and J. L. Stanford (2009). "Interest in genetic testing among affected men from hereditary prostate cancer families and their unaffected male relatives." Genet Med 11(5): 344-355. PMCID: 2683189.
  14. Hay, J., J. N. Harris, E. A. Waters, M. F. Clayton, L. Ellington, A. D. Abernethy and H. Prayor-Patterson (2009). "Personal communication in primary and secondary cancer prevention: evolving discussions, emerging challenges." J Health Commun 14 Suppl 1: 18-29.
  15. Marshall, D. and M. Hux (2009). "Design and Analysis Issues for Economic Analysis Alongside Clinical Trials." Med Care 7(Suppl 1): S14-20. PMCID: 19536012.
  16. Shaukat, A., M. Parekh, J. Lipscomb and U. Ladabaum (2009). "Can calcium chemoprevention of adenoma recurrence substitute or serve as an adjunct for colonoscopic surveillance?" Int J Technol Assess Health Care 25(2): 222-231. PMCID: 2972652.
  17. Johnson, F. R., A. F. Mohamed, S. Ozdemir, D. A. Marshall and K. A. Phillips (2010). "How does cost matter in health-care discrete-choice experiments?" Health Econ 20(3): 323-330.
  18. Johnson, F. R., S. Ozdemir and K. A. Phillips (2010). "Effects of simplifying choice tasks on estimates of taste heterogeneity in stated-choice surveys." Soc Sci Med 70(2): 183-190. PMCID: 3152257.
  19. Trosman, J. R., S. L. Van Bebber and K. A. Phillips (2010). "Coverage Policy Development for Personalized Medicine: Private Payer Perspectives on Developing Policy for the 21-Gene Assay." Journal of Oncology Practice 6(5): 238-242. PMCID: 2936466.
  20. Van Bebber, S. L., J. R. Trosman, S.-Y. Liang, G. Wang, D. A. Marshall, S. Knight and K. A. Phillips (2010). "Capacity building for assessing new technologies: approaches to examining personalized medicine in practice." Personalized Medicine 7(4): 427-439. PMCID: 3157083.
  21. Wang, G. and R. K. Kelley (2010). "KRAS mutational analysis for colorectal cancer: Application: Pharmacogenomic." PLoS Curr 2: RRN1175. PMCID: 2940138.
  22. Bowen, D. J., J. Harris, C. M. Jorgensen, M. F. Myers and A. Kuniyuki (2010). "Socioeconomic influences on the effects of a genetic testing direct-to-consumer marketing campaign." Public Health Genomics 13(3): 131-142.
  23. Cheung, E. L., A. D. Olson, T. M. Yu, P. Z. Han and M. S. Beattie (2010). "Communication of BRCA Results and Family Testing in 1,103 High-Risk Women." Cancer Epidemiology Biomarkers & Prevention 19(9): 2211-2219. PMCID: 3207738
  24. Elkin, E. B. and P. B. Bach (2010). "Cancer's next frontier: addressing high and increasing costs." JAMA 303(11): 1086-1087.
  25. Kelley, R. K. (2010) "What clinicians need to know about molecular markers in solid tumors." Medscape CME Oncology.
  26. Kelley, R. K. and A. P. Venook (2010). "Nonadherence to imatinib during an economic downturn." N Engl J Med 363(6): 596-598.
  27. Ladabaum, U., A. Ferrandez and A. Lanas (2010). "Cost-Effectiveness of Colorectal Cancer Screening in High Risk Spanish Patients: Use of a Validated Model to Inform Public Policy." Cancer Epidemiol Biomarkers Prev 19(11): 2765-2776. PMCID: 3159034.
  28. Marshall, D., S. E. McGregor and G. Currie (2010). "Measuring Preferences for Colorectal Cancer Screening: What are the Implications for Moving Forward?" The Patient: Patient-Centered Outcomes Research 3(2): 79-89.
  29. Kelley, R. K., S. L. Van Bebber, K. A. Phillips and A. P. Venook (2011). "Personalized Medicine and Oncology Practice Guidelines: A Case Study of Contemporary Biomarkers in Colorectal Cancer." Journal of the National Comprehensive Cancer Network 9(1): 13-25. PMCID: 3695822.
  30. Kelley, R. K. and A. P. Venook (2011). "Prognostic and Predictive Markers in Stage II Colon Cancer: Is There a Role for Gene Expression Profiling?" Clinical Colorectal Cancer 10(2): 73-80. PMCID: 3561586.
  31. Ladabaum, U., G. Wang, J. Terdiman, A. Blanco, M. Kuppermann, C. R. Boland, J. Ford, E. Elkin and K. A. Phillips (2011). "Strategies to Identify the Lynch Syndrome Among Patients With Colorectal Cancer." Annals of Internal Medicine 155(2): 69-79. PMCID: 3793257
  32. Liang, S.-Y., K. A. Phillips, G. Wang, C. Keohane, J. Armstrong, W. M. Morris and J. S. Haas (2011). "Tradeoffs of Using Administrative Claims and Medical Records to Identify the Use of Personalized Medicine for Patients With Breast Cancer." Medical Care 49(6): e1-e8 10.1097/MLR.1090b1013e318207e318287e. PMCID: 3383782.
  33. Ponce, N. A., J. Tsui, S. J. Knight, A. Afable-Munsuz, U. Ladabaum, R. A. Hiatt and J. S. Haas (2011). "Disparities in cancer screening in individuals with a family history of breast or colorectal cancer." Cancer. PMCID: 3262934
  34. Trosman, J. R., S. L. Van Bebber and K. A. Phillips (2011). "Health Technology Assessment and Private Payers' Coverage of Personalized Medicine." Journal of Oncology Practice 7(3S): 18s-24s. PMCID: 3092460.
  35. Wang, G., M. S. Beattie, N. A. Ponce and K. A. Phillips (2011). "Eligibility criteria in private and public coverage policies for BRCA genetic testing and genetic counseling." Genet Med 13(12): 1045-1050.
  36. Arar, N., S. J. Knight, S. M. Modell and A. M. Issa (2011). "The Genome-based Knowledge Management in Cycles model: a complex adaptive systems framework for implementation of genomic applications." Personalized Medicine 8(2): 191–205.
  37. Bridges, J. F. P., A. B. Hauber, D. Marshall, A. Lloyd, L. A. Prosser, D. A. Regier, F. R. Johnson and J. Mauskopf (2011). "Conjoint Analysis Applications in Health—a Checklist: A Report of the ISPOR Good Research Practices for Conjoint Analysis Task Force." Value in Health 14(4): 403-413.
  38. Elkin, E. B., D. A. Marshall, N. A. Kulin, I. L. Ferrusi, M. J. Hassett, U. Ladabaum and K. A. Phillips (2011). "Economic evaluation of targeted cancer interventions: critical review and recommendations." Genet Med 13(10): 853-860.
  39. Ferrusi, I. L., N. B. Leighl, N. A. Kulin and D. A. Marshall (2011). "Do Economic Evaluations of Targeted Therapy Provide Support for Decision Makers?" Journal of Oncology Practice 7(3S): 36s-45s. PMCID: 3092467.
  40. Haas, J., K. A. Phillips, S. Liang, M. Hassett, C. Keohane, E. Elkin, J. Armstrong and M. Toscano (2011). "Genomic Testing & Therapies for Breast Cancer in Clinical Practice." Journal of Oncology Practice 7(3S): e1s-e7s. PMCID: 3092459
  41. Haas, J. S., S. Y. Liang, M. J. Hassett, S. Shiboski, E. B. Elkin and K. A. Phillips (2011). "Gene expression profile testing for breast cancer and the use of chemotherapy, serious adverse effects, and costs of care." Breast Cancer Res Treat 130(2): 619-626. PMCID: 3590013.
  42. Kelley, R. K., G. Wang and A. P. Venook (2011). "Biomarker use in colorectal cancer therapy." J Natl Compr Canc Netw 9(11): 1293-1302. PMCID: 3696980.
  43. Lorizio, W., H. Rugo, M. S. Beattie, S. Tchu, T. Melese, M. Melisko, A. H. Wu, H. J. Lawrence, M. Nikoloff and E. Ziv (2011). "Pharmacogenetic testing affects choice of therapy among women considering tamoxifen treatment." Genome Med 3(10): 64. PMCID: 3239226.
  44. Odierna, D. H., A. Afable-Munsuz, O. Ikediobi, M. Beattie, S. Knight, M. Ko, A. Wilson and N. A. Ponce (2011). "Early developments in gene-expression profiling of breast tumors: potential for increasing black-white patient disparities in breast cancer outcomes?" Per Med 8(6): 669-679. PMCID: 3242007.
  45. Pletcher, M. J. and M. Pignone (2011). "Evaluating the clinical utility of a biomarker: a review of methods for estimating health impact." Circulation 123(10): 1116-1124. PMCID: 3138723.
  46. Beattie, M. S., G. Wang and K. A. Phillips (2012). "Differences in US healthcare coverage policies in BRCA testing and potential implications." Personalized Medicine 9(1): 5-8.
  47. Kuppermann, M., G. Wang, S. Wong, A. Blanco, P. Conrad, S. Nakagawa, J. Terdiman and U. Ladabaum (2012). "Preferences for Outcomes Associated with Decisions to Undergo or Forego Genetic Testing for Lynch Syndrome." Cancer 119(1):215-25.
  48. Ladabaum, U. and J. Ford (2012). "Lynch Syndrome in Patients with Colorectal Cancer: Finding the Needle in the Haystack." JAMA 308(15): 1581-1583.
  49. Mittmann, N., W. K. Evans, A. Rocchi, C. J. Longo, H.-J. Au, D. Husereau, N. B. Leighl, P. K. Isogai, M. D. Krahn, S. Peacock, D. Marshall, D. Coyle, S. C. Malfair Taylor, P. Jacobs and P. I. Oh (2012). "Guidelines for Health Technologies: Specific Guidance for Oncology Products in Canada." Value in Health 15(3): 580-585.
  50. Walsh, J., M. Arora, C. Hosenfeld, U. Ladabaum, M. Kuppermann and S. J. Knight (2012). "Preferences for genetic testing to identify hereditary colorectal cancer: perspectives of high-risk patients, community members, and clinicians." J Cancer Educ 27(1): 112-119.
  51. Wang, G., M. Kuppermann, B. Kim, K. A. Phillips and U. Ladabaum (2012). "Influence of patient preferences on the cost-effectiveness of screening for lynch syndrome." Am J Manag Care 18(5): e179-185. PMCID: 3348599.
  52. Ferrusi, I. L., C. C. Earle, M. Trudeau, N. B. Leighl, E. Pullenayegum, H. Khong, J. S. Hoch and D. A. Marshall (2013). "Closing the Personalized Medicine Information Gap: HER2 Test Documentation Practice." American Journal of Managed Care 19(1): 17-26.
  53. Phillips, K., J. Sakowski, S. Liang and N. Ponce (2013). "Economic Perspectives on Personalized Health Care and Prevention." Forum for Health Economics and Policy 16(2): 57-86.
  54. Reed Johnson, F., E. Lancsar, D. Marshall, V. Kilambi, A. Mühlbacher, D. A. Regier, B. W. Bresnahan, B. Kanninen and J. F. P. Bridges (2013). "Constructing Experimental Designs for Discrete-Choice Experiments: Report of the ISPOR Conjoint Analysis Experimental Design Good Research Practices Task Force." Value in Health 16(1): 3-13.
  55. Phillips KA, Ann Sakowski J, Trosman J, Douglas MP, Liang SY, Neumann P. The economic value of personalized medicine tests: what we know and what we need to know. Genet Med. 2014 Mar;16(3):251-7. PMCID: PMC3949119.
  56. Ponce NA, Ko M, Liang SY, Armstrong J, Toscano M, Chanfreau-Coffinier C, Haas JS. Early diffusion of gene expression profiling in breast cancer patients associated with areas of high income inequality. Health Aff (Millwood). 2015 Apr;34(4):609-15. PMID: 25847643.
  57. Bombard Y, Rozmovits L, Trudeau ME, Leighl NB, Deal K, Marshall DA. Patients' perceptions of gene expression profiling in breast cancer treatment decisions. Curr Oncol. 2014 Apr;21(2):e203-11. PMCID: PMC3997453.