Skip to main content Accessibility help
×
Home

Pharmacogenomic and pharmacogenetic-guided therapy as a tool in precision medicine: current state and factors impacting acceptance by stakeholders

  • GREGORY P. HESS (a1) (a2), EILEEN FONSECA (a3), RACHEL SCOTT (a4) and JESEN FAGERNESS (a4) (a5)

Summary

Pharmacogenetic/pharmacogenomic (PGx) testing is currently available for a wide range of health problems including cardiovascular disease, cancer, diabetes, autoimmune disorders, mental health disorders and infectious diseases. PGx contributes important information to the field of precision medicine by clarifying appropriate treatments for specific disease subtypes. Tangible benefits to patients including improved outcomes and reduced total health care costs have been observed. However, PGx-guided therapy faces many barriers to full integration into clinical practice and acceptance by stakeholders, whether practitioner, patient or payer. Each stakeholder has a unique perspective on the role of PGx testing, although all are similarly challenged with demonstrating or appraising its cost-to-benefit value. Coverage by insurers is a critical step in achieving widespread adoption of PGx testing. The acceleration of adoption of precision medicine in general and for PGx testing in particular will be determined by how quickly robust evidence can be accumulated that shows a return on investment for payers in terms of real dollars, for clinicians in terms of patient clinical responses, and for patients in terms of economic, health and quality of life outcomes. Trends in PGx testing utilization and uptake by payers in real-world practice are discussed; the role of pharmacoeconomics in assessing cost-effectiveness is highlighted using a case study in psychiatric care, and several issues that will affect adoption of PGx testing in the United States (US) over the next few years are reviewed.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Pharmacogenomic and pharmacogenetic-guided therapy as a tool in precision medicine: current state and factors impacting acceptance by stakeholders
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Pharmacogenomic and pharmacogenetic-guided therapy as a tool in precision medicine: current state and factors impacting acceptance by stakeholders
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Pharmacogenomic and pharmacogenetic-guided therapy as a tool in precision medicine: current state and factors impacting acceptance by stakeholders
      Available formats
      ×

Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

* Corresponding author: Gregory Hess, MD, MBA, MSc, Sr. Fellow LDI, Health Economics & Policy, University of Pennsylvania, Philadelphia, PA, USA, Chief Medical Officer and EVP, Symphony Health Solutions (SHS), Horsham, PA 19044, USA. Tel: 610-574-7250. Fax: 215-444-8832. E-mail: greg.hess@wharton.upenn.edu

References

Hide All
Aidsinfo NIH (2013). Ziagen (abacavir) prescribing information. Available at http://aidsinfo.nih.gov/drugs/257/ziagen/0/professional (Accessed 1 April 2015).
Amgen Corporation (2014). Vectibex (panitumumab) prescribing information. Available at pi.amgen.com/united_states/vectibix/vectibix_pi.pdf (Accessed 1 April 2015).
Astra Zeneca (2015). Lynparza (plaparib) prescribing information. Available at http://www.astrazeneca-us.com/cgi-bin/az_pi.cgi?product=lynparza&country=us&popup=no (Accessed 1 April 2015).
Austin, P. C. (2010). Statistical criteria for selecting the optimal number of untreated subjects matched to each treated subject when using many-to-one matching on the propensity score. American Journal of Epidemiology 172, 10921097.
Austin, P. C. (2011). Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharmaceutical Statistics 10, 150161.
Baser, O. (2006). Too much ado about propensity score models? Comparing methods of propensity score matching. Value Health 9, 377385.
Bhat, S., Dao, D. T., Terrillion, C. E., Arad, M., Smith, R. J., Soldatov, N. M. & Gould, T. D. (2012). CACNA1C (Cav1·2) in the pathophysiology of psychiatric disease. Progress in Neurobiology 99, 114.
Bristol-Myers Squibb (2013 a). Erbitux (cetuximab) prescribing information. Available at packageinserts.bms.com/pi/pi_erbitux.pdf (Accessed 1 April 2015).
Bristol-Myers Squibb (2013 b). Plavix (clopidogrel) prescribing information. Available at packageinserts.bms.com/pi/pi_plavix.pdf (Accessed 1 April 2015).
Burroughs, V. J., Maxey, R. W. & Levy, R. A. (2002). Racial and ethnic differences in response to medicines: towards individualized pharmaceutical treatment. Journal of the National Medical Association 94, 126.
Carlson, J., Garrison, L. & Sullivan, S. (2009). Paying for outcomes: innovative coverage and reimbursement schemes for pharmaceuticals. Journal of Managed Care Pharmacy 15, 683687.
CDC (2013). Health, United States 2013 With Special Feature on Prescription DrugsCenters for Disease Control; Figure 21. http://www.cdc.gov/nchs/data/hus/hus13.pdf (Accessed 1 April 2015).
Clancy, J. P., Johnson, S. G., Yee, S. W., McDonagh, E. M., Caudle, K. E., Klein, T. E., Cannavo, M. & Giacomini, K. M. (2014). Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype. Clinical Pharmacology and Therapeutics 95, 592597.
CMS (2014 a). Centers for Medicare & Medicaid Services. Available at http://www.cms.gov/Medicare/Coverage/Coverage-with-Evidence-Development/ (Accessed 1 April 2015).
CMS & HHS (2014 b). Medicare program; revisions to payment policies under the Physician Fee Schedule, Clinical Laboratory Fee Schedule, access to identifiable data for the Center for Medicare and Medicaid Innovation Models & other revisions to Part B for CY 2015. Final rule with comment period. Federal Register 79, 6754768010.
Cohen, J., Wilson, A. & Manzolillo, K. (2013). Clinical and economic challenges facing pharmacogenomics. The Pharmacogenomics Journal 13, 378388.
CPIC (2015). CPIC: Clinical Pharmacogenetics Implementation Consortium. Dosing Guidelines. Available at http://www.pharmgkb.org/view/dosing-guidelines.do?source=CPIC# (Accessed 1 April 2015).
Deverka, P. A. (2009). Pharmacogenomics, evidence, and the role of payers. Public Health Genomics 12, 149157.
Dowsett, M., Cuzick, J., Wale, C., Forbes, J., Mallon, E. A., Salter, J., Quinn, E., Dunbier, A., Baum, M., Buzdar, A., Howell, A., Bugarini, R., Baehner, F. L. & Shak, S. (2010). Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. Journal of Clinical Oncology 28, 18291834.
Dressler, L. & Terry, S. (2009). How will GINA influence participation in pharmacogenomics research and clinical testing? Clinical Pharmacology and Therapeutics 86, 472475.
Epstein, R. S., Frueh, F. W., Geren, D., Hummer, D., McKibbin, S., O'Connor, S., Randhawa, G. & Zelman, B. (2009). Payer perspectives on pharmacogenomics testing and drug development. Pharmacogenomics 10, 149151.
Evans, W. E. & McLeod, H. L. (2003). Pharmacogenomics – drug disposition, drug targets, and side effects. The New England Journal of Medicine 348, 538549.
Fagerness, J., Fonseca, E., Hess, G., Scott, R., Gardner, K. R., Koffler, M., Fava, M., Perlis, R., Brennan, F. X. & Lombard, J. (2014). Pharmacogenetic-guided psychiatric intervention associated with increased adherence and cost savings. The American Journal of Managed Care 20, e146e156.
FDA (2014 a). US Food and Drug Administration List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools). Available at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm (Accessed January 2015).
FDA (2014 b). US Food and Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labeling. Available at http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm (Accessed 1 April 2015).
FDA (2015 a). US Food and Drug Administration Database of Diagnositc Test Kits. Warfarin test kits. Available at http://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm (Accessed 1 April 2015).
FDA (2015 b). US Food and Drug Administration Guidance on Laboratory Developed Tests. Available at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm407296.htm (Accessed 1 April 2015).
Flockhart, D. A., O'Kane, D., Williams, M. S., Watson, M. S., Gage, B., Gandolfi, R., King, R., Lyon, E., Nussbaum, R., Schulman, K. & Veenstra, D. (2008). Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. Genetics in Medicine 10, 139150.
Freedman, A. N., Sansbury, L. B., Figg, W. D., Potosky, A. L., Weiss Smith, S. R., Khoury, M. J., Nelson, S. A., Weinshilboum, R. M., Ratain, M. J., McLeod, H. L., Epstein, R. S., Ginsburg, G. S., Schilsky, R. L., Liu, G., Flockhart, D. A., Ulrich, C. M., Davis, R. L., Lesko, L. J., Zineh, I., Randhawa, G., Ambrosone, C. B., Relling, M. V., Rothman, N., Xie, H., Spitz, M. R., Ballard-Barbash, R., Doroshow, J. H. & Minasian, L. M. (2010). Cancer pharmacogenomics and pharmacoepidemiology: setting a research agenda to accelerate translation. Journal of the National Cancer Institute 102, 16981705.
Genentech (2014). Herceptin (trastuzumab) prescribing information. Available at http://www.gene.com/download/pdf/herceptin_prescribing.pdf (Accessed 1 April 2015).
Genentech (2015). Zelboraf (vemurafenib) prescribing information. http://www.gene.com/download/pdf/zelboraf_prescribing.pdf (Accessed 1 April 2015).
Graf, M., Needham, D., Teed, N. & Brown, T. (2013). Genetic testing insurance coverage trends a review of publicly available policies from the largest US payers. Personalized Medicine 10, 235243.
Guyatt, G. H., Akl, E. A., Crowther, M., Gutterman, D. D. & Schuunemann, H. J. (2012). Executive summary: Antithrombotic Therapy And Prevention Of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141, 7S47S.
Heil, S. G. (2013). Epigenetic techniques in pharmacogenetics. Methods in Molecular Biology 1015, 179188.
Holmes, D. R. Jr, Dehmer, G. J., Kaul, S., Leifer, D., O'Gara, P. T. & Stein, C. M. (2010). ACCF/AHA clopidogrel clinical alert: approaches to the FDA “boxed warning”: a report of the American College of Cardiology Foundation Task Force on clinical expert consensus documents and the American Heart Association endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Journal of the American College of Cardiology 56, 321341.
Hresko, A. & Haga, S. B. (2012). Insurance coverage policies for personalized medicine. Journal of Personalized Medicine 2, 201216.
Kao, C. F., Fang, Y. S., Zhao, Z. & Kuo, P. H. (2011). Prioritization and evaluation of depression candidate genes by combining multidimensional data resources. PLoS ONE 6, e18696.
Kato, M. & Serretti, A. (2010). Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Molecular Psychiatry 15, 473500.
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., Rush, A. J., Walters, E. E. & Wang, P. S. (2003). The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 289, 30953105.
Kirchheiner, J., Nickchen, K., Bauer, M., Wong, M. L., Licinio, J., Roots, I. & Brockmoller, J. (2004). Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Molecular Psychiatry 9, 442473.
Lazarou, J., Pomeranz, B. H. & Corey, P. N. (1998). Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 279, 12001205.
Lencz, T., Robinson, D. G., Napolitano, B., Sevy, S., Kane, J. M., Goldman, D. & Malhotra, A. K. (2010). DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia. Pharmacogenetics and Genomics 20, 569572.
Luo, Z., Gardiner, J. C. & Bradley, C. J. (2010). Applying propensity score methods in medical research: pitfalls and prospects. Medical Care Research and Review 67, 528554.
Meckley, L. M. & Neumann, P. J. (2009). Personalized medicine: factors influencing reimbursement. Health Policy 94, 91100.
NCI (2014). National Cancer Institute: Cancer Pharmacoepidemiology and Pharmacogenomics. Available at http://epi.grants.cancer.gov/pharm/ (Accessed 20 April 2015).
NIH (2014). National Institute of Health, National Center for Advancing Translational Medicine. Available at www.ncats.nih.gov/news-and-events/e-news/vol03-iss04/july2014.html (Accessed 20 April 2015).
NIH (2015). The Genetic Information Nondiscrimination Act (GINA). Available at http://ghr.nlm.nih.gov/spotlight=thegeneticinformationnondiscriminationactgina (Accessed 20 April 2015).
Novartis (2014). Gleevec (imatinib) prescribing information. Available at http://www.pharma.us.novartis.com/product/pi/pdf/gleevec_tabs.pdf (Accessed 20 April 2015).
Pfizer (2014). Xalkori (crizotinib) prescribing information. Available at http://labeling.pfizer.com/ShowLabeling.aspx?id=676 (Accessed 20 April 2015).
Porcelli, S., Drago, A., Fabbri, C., Gibiino, S., Calati, R. & Serretti, A. (2011). Pharmacogenetics of antidepressant response. Journal of Psychiatry and Neuroscience 36, 87113.
Porcelli, S., Fabbri, C. & Serretti, A. (2012). Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. European Neuropsychopharmacology 22, 239258.
Psychiatric GWAS Consortium Bipolar Disorder Working Group (2011). Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nature Genetics 43, 977983.
Ramsey, L. B., Johnson, S. G., Caudle, K. E., Haidar, C. E., Voora, D., Wilke, R. A., Maxwell, W. D., McLeod, H. L., Krauss, R. M., Roden, D. M., Feng, Q., Cooper-DeHoff, R. M., Gong, L., Klein, T. E., Wadelius, M. & Niemi, M. (2014). The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clinical Pharmacology and Therapeutics 96, 423428.
Rosove, M. H. & Grody, W. W. (2009). Should we be applying warfarin pharmacogenetics to clinical practice? No, not now. Annals of Internal Medicine 151, 270273, W95.
Salloum, N. C., McCarthy, M. J., Leckband, S. G. & Kelsoe, J. R. (2014). Towards the clinical implementation of pharmacogenetics in bipolar disorder. BMC Medicine 12, 90.
Scott, S. A., Sangkuhl, K., Stein, C. M., Hulot, J. S., Mega, J. L., Roden, D. M., Klein, T. E., Sabatine, M. S., Johnson, J. A. & Shuldiner, A. R. (2013). Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clinical Pharmacology and Therapeutics 94, 317323.
Sorich, M. J., Wiese, M. D., O'Shea, R. L. & Pekarsky, B. (2013). Review of the cost effectiveness of pharmacogenetic-guided treatment of hypercholesterolaemia. Pharmacoeconomics 31, 377391.
Souery, D., Papakostas, G. I. & Trivedi, M. H. (2006). Treatment-resistant depression. The Journal of Clinical Psychiatry 67(Suppl 6), 1622.
Spear, B. B., Heath-Chiozzi, M. & Huff, J. (2001). Clinical application of pharmacogenetics. Trends in Molecular Medicine 7, 201204.
Talameh, J. A. & Kitzmiller, J. P. (2014). Pharmacogenetics of statin-induced myopathy: a focused review of the clinical translation of pharmacokinetic genetic variants. Journal of Pharmacogenomics & Pharmacoproteomics 5, pii: 128.
Tansey, K. E., Guipponi, M., Hu, X., Domenici, E., Lewis, G., Malafosse, A., Wendland, J. R., Lewis, C. M., McGuffin, P. & Uher, R. (2013). Contribution of common genetic variants to antidepressant response. Biological Psychiatry 73, 679682.
Thompson, P. D., Clarkson, P. & Karas, R. H. (2003). Statin-associated myopathy. JAMA 289, 16811690.
Tunis, S. R. & Pearson, S. D. (2006). Coverage options for promising technologies: Medicare's ‘coverage with evidence development’. Health Affairs (Millwood) 25, 12181230.
Vertex (2014). Kalydeco (ivacaftor) tablets prescribing information. Vertex Pharmaceuticals Incorporated. Available at pi.vrtx.com/files/uspi_ivacaftor.pdf (Accessed 20 April 2015).
Warden, D., Rush, A. J., Trivedi, M. H., Fava, M. & Wisniewski, S. R. (2007). The STAR*D Project results: a comprehensive review of findings. Current Psychiatry Reports 9, 449459.
Yaghjyan, L., Colditz, G. A., Collins, L. C., Schnitt, S. J., Rosner, B., Vachon, C. & Tamimi, R. M. (2011). Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to tumor characteristics. Journal of the National Cancer Institute 103, 11791189.
Zhang, J. P., Lencz, T. & Malhotra, A. K. (2010). Dopamine D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis. American Journal of Psychiatry 167, 763772.

Pharmacogenomic and pharmacogenetic-guided therapy as a tool in precision medicine: current state and factors impacting acceptance by stakeholders

  • GREGORY P. HESS (a1) (a2), EILEEN FONSECA (a3), RACHEL SCOTT (a4) and JESEN FAGERNESS (a4) (a5)

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.