Skip to main content
PMC home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2016 Apr 1.
Published in final edited form as: J Manag Care Spec Pharm. 2015 Apr;21(4):346–352. doi: 10.18553/jmcp.2015.21.4.346

Challenges to Integrating Pharmacogenetic Testing into Medication Therapy Management

Susanne B Haga 1,✉, Nancy M Allen LaPointe 2, Jivan Moaddeb 1
PMCID: PMC4522310  NIHMSID: NIHMS709730  PMID: 25803768

Abstract

Background

Some have proposed the integration of pharmacogenetic (PGx) testing into medication therapy management (MTM) to enable further refinement of treatment(s) to reduce risk of adverse responses and improve efficacy. PGx testing involves the analysis of genetic variants associated with therapeutic or adverse response and may be useful in enhancing the ability to identify ineffective and/or harmful drugs or drug combinations. This “enhanced” MTM might also reduce patient concerns about side effects and increase confidence that the medication is effective, addressing two key factors that impact patient adherence - concern and necessity. However, the feasibility and effectiveness of the integration of PGx testing into MTM in clinical practice has not yet been determined.

Objectives

In this paper, we consider some of the challenges to the integration and delivery of PGx testing in MTM services.

What is already known about this subject

While the addition of pharmacogenetic testing has been suggested, little literature exists exploring the challenges or feasibility of doing so.

Introduction

Medication therapy management (MTM) and comprehensive medication reviews (CMR) have been shown effective in reducing inappropriate medication use, adverse events due to drug-drug interactions, and medication non-adherence.1–3 Pharmacist review of a patient’s medication regimen, including indications for the medications, adverse event profile, and pharmacokinetic and pharmacodynamic properties, may identify ineffective and/or harmful drugs and drug combinations that can be changed and lead to improved health outcomes.3 Some have proposed the integration of pharmacogenetic (PGx) testing into MTM4,5 to enable further refinement of treatment(s) to reduce risk of adverse responses and improve efficacy.6,7 PGx testing involves the analysis of genetic variants associated with therapeutic or adverse response and may be useful in enhancing the ability to identify potentially ineffective and/or harmful drugs or drug combinations. This “enhanced” MTM might also reduce patient concerns about side effects and increase confidence that the medication is effective, addressing two key factors that impact patient adherence – concern and necessity.8 However, the feasibility and effectiveness of the integration of PGx testing into MTM in clinical practice has not yet been determined. In this paper, we consider some of the potential benefits and challenges to the integration and delivery of PGx testing in MTM services.

Overview of MTM

As the safe and effective self-management of medications has become increasingly recognized as a key component to improving health, MTM services have transitioned from primarily patient education and counseling to systematic and coordinated processes for comprehensive medication management.9 Patients with chronic medical condition(s) likely have numerous healthcare providers and medications and as a result, may inadvertently be prescribed multiple drugs within the same medication classes or drugs that may interact with each other, leading to increased risk of adverse events, failure to achieve therapeutic goals, discontinuation of medications, or reduced quality of life. Effective MTM aims to reconcile medication discrepancies and improve medication management.

Though practices can vary,10 MTM services should include five core elements: 1) medication therapy review (MTR), 2) personal medication record (PMR), 3) medication-related action plan (MAP), 4) intervention and/or referral, and 5) documentation and follow-up.11 Typically conducted by a pharmacist, MTM can serve as an educational tool for physicians and patients, and provide a personalized strategy for patients to improve adherence with their medications given their personal, economic, or other challenges with medication self-management. If modifications to a patient’s current drug regimen are warranted, the pharmacist can also act as a liaison with the prescriber on behalf of the patient.

In 2003, the U.S. Medicare Prescription Drug, Improvement, and Modernization Act established a prescription drug benefit (Part D) that included a requirement for participating health plans to offer MTM services to eligible patients beginning in 2006.12 Part D enrollees who had multiple chronic diseases, taking multiple Part D drugs, and likely to exceed $3,144 in annual costs (threshold for 2013) for covered Part D drugs (§ 423.153(d)(1)) were considered eligible for these MTM services. However, eligible enrollees in many plans initially had to opt in to receive the MTM services resulting in only a small proportion of eligible patients receiving these services on prescription medications.13 This provision has now been changed so that eligible enrollees are offered MTM services unless they opt out with the hope that a greater proportion of patients will receive these services. As of 2013, there were 645 active Part D contracts with an approved MTM program.14 In addition, several state Medicaid plans and private, non-Medicare health plans provide access to and payment for MTM services.

PGx Testing

PGx testing for patients’ genetic likelihood for an adverse response or to determine suitability for a targeted drug is at the forefront of the personalized medicine movement and gradually moving from specialty medications (e.g., oncology) to more broadly prescribed medications (e.g., codeine, statins, or warfarin). To date, the drug labels of 137 medications include PGx-related information15 and it has been estimated that 16 percent of medications prescribed in primary care are impacted by PGx variants.16 Knowledge of a patient’s genetic predisposition for an adverse response or therapeutic response can augment current clinical predictors to improve drug selection and response at the time of prescribing. For example, testing for HLA-B*57:01 is currently recommended to identify patients at risk of experiencing hypersensitivity reactions linked to abacavir.17–19 The Food and Drug Administration has issued warnings about potential codeine toxicity leading to adverse events or even death in those with a genetic variant of the CYP2D6 gene resulting in very rapid and complete conversion of codeine into morphine in children and nursing mothers.20–22 The utility and hence, integration, of PGx information for other medications are still actively under investigation. For example, use of CYP2C9/VKORC1testing to inform warfarin dosing is currently under investigation for its usefulness in clinical settings to achieving INR goals and reducing potential adverse events associated with out of range INRs. 23–25

At this time, the delivery model of PGx testing is unclear, with different approaches currently under investigation26,27,28. In general, PGx tests can be ordered at the time a medication is prescribed or preemptively for anticipated future treatment.27 Health professionals involved in the delivery of PGx testing may include the laboratorian, prescriber, pharmacist, and potentially a genetic counselor. With development of new and cheaper testing technologies,29,30 it is possible that patients’ genetic predisposition for a panel of drugs will be ascertained through a single test and results consulted as new medications are prescribed.

Challenges to Integrating PGx into MTM Services

The addition of PGx testing to current MTM services would align well with the goals of MTM and fit within the scope of information discussed and reviewed between the patient and MTM provider. However, given barriers to the provision of current MTM services, it is important to consider the feasibility of adding this new element. In particular, the successful integration of PGx into MTM services likely faces multiple challenges at the health system, provider, and patient levels. Our discussion will primarily focus on challenges to the integration of PGx testing into MTM from the health system and pharmacist perspectives. We recognize that the extent and scope of some of these challenges may be heavily impacted by the type of health system (e.g., integrated vs. non-integrated) and the extent to which pharmacists are utilized or valued in the broader health care system. We identify and discuss six potential challenges to the integration of PGx testing into MTM services in the U.S. health care environment. These challenges were identified from a review of experiences encountered by implementation of MTM and other pharmacy services, the limited experience of early physician adopters and prospective users of PGx testing31,32. This list is likely not comprehensive and new issues may be identified as more pharmacies begin to offer this service. We will provide a general overview of the challenges rather than attempt to delineate challenges in different types of healthcare systems.

1. Timing of and Access to PGx testing

Pharmacists may provide MTM services in a range of settings, most commonly in a hospital, outpatient clinic, or community pharmacy setting.33 As a result, each setting may present different challenges in integrating PGx testing into MTM services. As the majority of MTM services are currently delivered by community pharmacists or clinic-based pharmacists, we will limit most of our discussion to these settings.

As mentioned previously, PGx tests may be ordered at the time a drug is prescribed or preemptively when the patient is healthy and stored for future use. Regardless of when the test is ordered, a clinic-based pharmacist would likely have the most rapid and convenient access to the test results and patient’s complete medical record. In contrast, a community pharmacist would have to rely on the patient to inform the pharmacist of their test result or obtain a copy of the results from the patient or physician. However, patient recall of PGx test results may be challenging for some given the novelty of testing and unfamiliarity with terms such as ‘extensive metabolizer’ or test outcomes such as “genotype.” Acquiring a copy of the report from patients or providers may also be challenging as patients may not have been given a written report that they can share and physicians may be difficult to contact and reluctant to share laboratory reports with community pharmacists. A health information exchange (HIE) may be a feasible strategy for sharing test results amongst providers, including pharmacists, and could reduce duplicate testing by multiple providers 34,35, though a minority of states do not allow clinical laboratory results to be returned to a pharmacist.36 Although patients are generally supportive of HIE, some have expressed concerns about their privacy and the security of the HIE 37,38.

Alternatively, clinic-based pharmacists could order PGx tests through collaborative practice agreements (CPAs), also known as Collaborative Drug Therapy Management. CPAs enable pharmacists to provide a variety of services in collaboration with other health providers (typically physicians) and may allow pharmacists to order PGx testing rather than depending on physician providers. Most states have enacted legislation permitting pharmacists to provide a range of drug therapy management services through CPAs, though the scope varies from state-to-state.39,40 In 2013, 31 states permitted pharmacists to order clinical laboratory tests under a CPA (APhA).41 In some cases, credentialing may be required; for example, only pharmacists certified as diabetes educators (CDEs) can order point-of-care tests.42

2. Extended MTM sessions

A typical initial MTM session may last between 30 minutes to one hour with follow-up appointments, as necessary.3,43,44 If the pharmacist recommends PGx testing during the MTM, additional time will be needed to introduce PGx testing to the patient and discuss the purpose of the test, risks and limitations, and alternatives. In addition, a follow-up visit will be necessary to review the PGx results and their significance for the patient’s drug therapy. While care may be improved for some patients with the inclusion of PGx testing, the additional time required to provide this service may result in a relative reduction in other MTM services. Even without PGx testing, it has been recognized that expanded patient eligibility for MTM consultations warrant additional service delivery options to address potential workforce shortages in some geographic areas. The National Committee for Quality Assurance recommended that the 2006 Sound Medication Therapy Management Programs (Version 1.0) revise its position that the preferred delivery MTM model be face-to-face.45 In 2013, 92% of Part D programs offered CMR consultation by phone, 42% also offered in-person consultations (up from 28% in 2012), and 16% of programs offered CMR consultations through tele-health (up from 1% in 2012).14 Several studies have demonstrated the effectiveness of phone MTM in addressing medication-related issues46–49 and patient satisfaction.49 However, it is unclear whether MTM plus PGx testing can be fully delivered via tele-health, given the amount of new and potentially complex information that would be discussed.

3. Information Technology (IT)

The storage and portability of a patient’s PGx results will impact level of utilization. Information technology can greatly enable rapid access to patients’ prescription history and clinical test results.50 A clinic-based pharmacist, as described above, could have access to PGx results through the clinic or health system’s electronic health record. Likewise, MTM services could be documented in the electronic health record and recommendations based on the test results could also be contained within the electronic health record. However, the clinic-based pharmacist would likely have no to limited access to data on actual prescriptions filled or PGx tests ordered outside of his/her health system, except in a very small number of locations where these data might be accessible through an HIE.

Community pharmacists usually do not have access to a health system’s electronic health record. Instead, community pharmacists often have a local (or pharmacy chain-specific) IT system focused on prescription fills with a separate IT platform for MTM services. The prescription database and MTM application can be locally integrated in order to facilitate completion of a medication reconciliation process that uses health plan prescription data and local pharmacy prescription data, especially for patients that use multiple pharmacies for their prescription medications. Currently, health IT tools for MTM services are primarily used to facilitate identification of patients eligible for reimbursable MTM services, complete medication reconciliation, and process reimbursement for pharmacists’ MTM services.51 PGx test results obtained from the patient or provider could be manually entered into most of the MTM systems; however, access to these data by pharmacists in other locations may be non-existent or very limited. Alternately, if testing is ordered by a pharmacist in the community setting, storage of the result in the community pharmacy database is also possible as community pharmacists already have experience storing other lab results for drugs such as clozapine. Therefore, a similar record of PGx results could be established and accessed for each new prescription. However, this also limits utilization of the PGx test results to that particular pharmacy. This discontinuity of care may particularly affect patients that obtain prescription drugs from multiple pharmacies for various reasons (cost, type of insurance, convenience).52 In addition, the lack of connectivity with the prescriber with these IT systems impacts continuity of care.

In addition, even if pharmacists had access to PGx results, clinical decision supports (CDS) may be needed to promote appropriate interpretation and utilization of results. Some CDS tools have been developed to assist physicians in considering testing or dosing/drug selection based on test results.28,53 To our knowledge, no similar CDS has been explored for pharmacists.

4. Training & Workforce

In 2012, approximately 286,000 pharmacists are estimated to be practicing, primarily in community pharmacies (43%) and hospitals (23%).54 Likelihood and interest in providing MTM services is predicted by pharmacist training and comfort level.55 The Accreditation Council for Pharmacy Education (ACPE) currently requires colleges and schools of pharmacy to provide basic MTM training.56 To fulfill this requirement, a range of training programs for MTM have been developed and implemented in pharmacy schools and continuing education programs.57–59 If pharmacists are ordering lab tests, they will also require additional training on communicating test results. One of the issues raised by pharmacists with new testing programs such as HIV testing are discomfort with communicating positive results.60

The delivery of PGx testing as part of an MTM service will require additional training of pharmacists. Currently, pharmacists report low knowledge and confidence in using PGx information for adjusting dose or drug selection.61,62 Several professional pharmacy organizations have called for the addition of PGx material into pharmacy curricula and schools have positively responded,63 exploring numerous approaches.64–66 For practicing pharmacists, continuing education will help promote awareness of PGx, but more intensive training may be required if pharmacists offer PGx testing given the complexity of the material.67 Since decisions regarding changes to prescriptions must be approved by the prescriber, physicians, physician assistants and nurse practitioners must also be knowledgeable to understand the PGx-guided recommendations to act appropriately. Physicians have reported low knowledge about PGx68–70 and are likely to have had limited exposure in medical schools.71 Several professional nursing organizations have recommended PGx content in nursing programs72 and genetics core competencies recommendations,73,74 though more effort is also still needed to implement these recommendations into nursing programs.75

5. Standards-setting

Just as standards have been developed for MTM services in general, it will also be important to set standards for integrating PGx testing into MTM practice. In particular, given the relative novelty of PGx testing, it will be important to define what information should be delivered prior to testing and how to communicate the test results effectively and efficiently during the MTM session. Several factors may impact patient-provider communication about PGx testing, including provider knowledge, time, and patient interest. Since the genetics of drug response may be unfamiliar to patients, we suggest that a standardized teaching approach may be warranted to ensure the sufficient information is clearly presented to enhance patient understanding.

In addition, with the pharmacist’s expanded role in interpreting and communicating PGx test results with patients and other providers, pharmacist liability would need to be addressed as this expansion of current MTM services may be viewed as a potentially higher risk activity in our litigious society. Some have discussed the potential for liability and its potential adverse impact on provider behaviors regarding PGx testing.76,77 When multiple providers are involved in treatment decisions, pharmacist liability appears to be limited to medication dispensation (Moore & Matlock, 2014).78 However, courts have begun to recognize the broader roles of pharmacists beyond dispensation and applied a ‘reasonable professional” standard.79 Correspondence with the prescriber and patient are important elements in reducing liability80 and a copy of the MAP including the PGx test results (or summary for patients) should be shared with both parties If the pharmacist has knowledge of a pateint’s PGx test results, they may have a duty to warn patients of potential risks for current and future medications.81

6. Reimbursement

Another barrier to the provision of MTM services is reimbursement.82–84 Depending on the setting, pharmacist billing can vary33 and new models continue to be explored.85,86 For example, in ambulatory care clinics, billing for pharmacist MTM services may be submitted as incident-to physician care charges.87,88 With the establishment of pharmacists’ Current Procedural Terminology billing codes (CPT codes 99605, 99606, and 99607), pharmacists may also directly bill for services. The variability in payer fee schedules and actual reimbursement rates 89 further add to pharmacists’ concerns about appropriate reimbursement for MTM services. The current confusion regarding billing codes and additional time required to complete documentation and billing indicate pharmacists’ need for additional support to obtain reimbursement.84,90 Indeed, a survey conducted in 2011 found that a substantial proportion of pharmacists reported not billing for MTM services.33,91 Others believe that Medicare Part D reimbursement is too low for pharmacy services including MTM.92 The inclusion of PGx testing into MTM with the anticipated additional time needed to discuss testing, collect and ship the sample, re-contact the patient, and consult with the prescriber may further complicate reimbursement since pharmacist CPT codes do not account for complexity of MTM service and can only be used for in-person MTM.

Conclusion

The growth in PGx research and the readily available means for conducting PGx testing in non-traditional settings provides patients and clinicians with new ways to manage medications. Pharmacists are uniquely trained in using in-depth knowledge of drugs and their properties to safely and effectively select and manage complex medication regimen. PGx testing can provide a new level of detail for potentially even better drug selection and management decisions. Pharmacist-delivered services, especially in community practice settings continue to evolve to meet the demand from patients, payors, and other health care providers to improve medication management, including standardization and enhancements in MTM services. Now may be an opportune time to consider the feasibility of integrating PGx testing into MTM and to establish a niche for pharmacists in the personalized medicine movement. As with any new service, the integration of PGx testing into MTM conducted by pharmacists faces several challenges. In this paper, we explored some of those challenges to stimulate discussion on potential next steps. Agreement from multiple stakeholders on the feasibility and value of this service, tested and proven models for implementation and dissemination, and an established business case are needed to advance this potential new method of medication management. This will likely require new partnerships between pharmacists and physician groups, diagnostic laboratories, and software vendors and engagement of professional societies and/or consortium of pharmacies to develop this potential new opportunity. Despite the challenges, we envision community pharmacists are uniquely poised, with respect to their expertise of drugs, frequent interaction with patients, and interface between prescribers and patients, to play a key role in delivering PGx testing. We believe that patient engagement through a service like MTM will be necessary, particularly during the early stages of implementation of PGx testing in general, to increase patient familiarity with testing and understanding of the results for current and future medication needs. As additional tests may be performed for a given patient, the level of engagement needed may be less. As the practice of MTM and PGx testing matures, early integration of the two tools may benefit all stakeholders

Table.

Summary of potential challenges to provision of MTM plus PGx testing service by community pharmacists.

  1. Timing of and Access to PGx Testing

    • Timing PGx testing for making optimal drug decisions

    • Access to PGx test results done in various clinical care settings

    • Ability of pharmacists to order PGx testing

  2. Extended MTM Sessions

    • Pharmacist time constraints in community practice

    • Uncertain added time needed for Initial and follow-up session needed to introduce testing/discuss test results

    • Uncertain feasibility of discussing PGx testing by phone versus face-to-face

  3. Information Technology

    • Potentially limited access to patient’s electronic health record

    • Need to integrate PGx test information into health IT tools for MTM

  4. Training & Workforce

    • Limited PGx education in pharmacy curriculum

    • Need for continuing education as PGx field grows

  5. Standards-Setting

    • Development of standards for integrating PGx testing into MTM practice to provide consistent and documentable added value

    • Consideration of pharmacist liability

  6. Reimbursement

    • Obtaining adequate reimbursement for MTM plus PGx testing service

Open in a new tab

References

  • 1.DiMatteo MR, Giordani PJ, Lepper HS, Croghan TW. Patient adherence and medical treatment outcomes: a meta-analysis. Med Care. 2002;40(9):794–811. doi: 10.1097/00005650-200209000-00009. [DOI] [PubMed] [Google Scholar]
  • 2.Pellegrino AN, Martin MT, Tilton JJ, Touchette DR. Medication therapy management services: definitions and outcomes. Drugs. 2009;69(4):393–406. doi: 10.2165/00003495-200969040-00001. [DOI] [PubMed] [Google Scholar]
  • 3.Ramalho de Oliveira D, Brummel AR, Miller DB. Medication therapy management: 10 years of experience in a large integrated health care system. Journal of managed care pharmacy : JMCP. 2010;16(3):185–195. doi: 10.18553/jmcp.2010.16.3.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Reiss SM. Integrating pharmacogenomics into pharmacy practice via medication therapy management. J Am Pharm Assoc. 2011;51(6):e64–74. doi: 10.1331/JAPhA.2011.11543. [DOI] [PubMed] [Google Scholar]
  • 5.Shaw L, Burckhard G. Therapeutic drug monitoring and pharmacogenetics interface considerations. In: Valdes R, Payne DA, Linder MW, editors. Laboratory medicine practice guidelines: guidelines and recommendations for laboratory analysis and application of pharmacogenetics to clinical practice. Washington, DC: National Academy of Clinical Biochemistry (NACB); 2010. pp. 29–34. [Google Scholar]
  • 6.Gervasini G, Benitez J, Carrillo JA. Pharmacogenetic testing and therapeutic drug monitoring are complementary tools for optimal individualization of drug therapy. European journal of clinical pharmacology. 2010;66(8):755–774. doi: 10.1007/s00228-010-0857-7. [DOI] [PubMed] [Google Scholar]
  • 7.Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clinical pharmacology and therapeutics. 2011;89(3):464–467. doi: 10.1038/clpt.2010.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Haga SB, Lapointe NM. The potential impact of pharmacogenetic testing on medication adherence. The pharmacogenomics journal. 2013;13(6):481–483. doi: 10.1038/tpj.2013.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Barnett MJ, Frank J, Wehring H, et al. Analysis of pharmacist-provided medication therapy management (MTM) services in community pharmacies over 7 years. Journal of managed care pharmacy : JMCP. 2009;15(1):18–31. doi: 10.18553/jmcp.2009.15.1.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Touchette DR, Masica AL, Dolor RJ, et al. Safety-focused medication therapy management: a randomized controlled trial. J Am Pharm Assoc. 2012;52(5):603–612. doi: 10.1331/JAPhA.2012.12036. [DOI] [PubMed] [Google Scholar]
  • 11.Association AP. Medication therapy management in pharmacy practice: core elements of an MTM service model (version 2.0) J Am Pharm Assoc. 2008;48(3):341–353. doi: 10.1331/JAPhA.2008.08514. [DOI] [PubMed] [Google Scholar]
  • 12.CMS. Medicare Prescription Drug Benefit Final Rule: 42 CFR Parts 400, 403, 411, 417, and 423 Medicare Program. Federal Register. 2005;70(18):4193–4585. [PubMed] [Google Scholar]
  • 13.Rucker NL. Medicare Pard D’s Medication Therapy Management: Shifting from Neutral to Drive. AARP Public Policy Institute; 2012. Insight on the Issues(64) [Google Scholar]
  • 14.CMS. [Accessed March 12, 2014];Medicare Part D Medication Therapy Management (MTM) Programs: Fact Sheet Summary of 2013 MTM Programs. 2013 http://www.cms.gov/Medicare/Prescription-Drug-Coverage/PrescriptionDrugCovContra/Downloads/CY2013-MTM-Fact-Sheet.pdf.
  • 15.FDA. [Accessed March 12, 2014];Table of Pharmacogenomic Biomarkers in Drug Labels. 2014 http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm.
  • 16.Grice GR, Seaton TL, Woodland AM, McLeod HL. Defining the opportunity for pharmacogenetic intervention in primary care. Pharmacogenomics. 2006;7(1):61–65. doi: 10.2217/14622416.7.1.61. [DOI] [PubMed] [Google Scholar]
  • 17.Martin MA, Hoffman JM, Freimuth RR, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update. Clin Pharmacol Ther. 2014 doi: 10.1038/clpt.2014.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Saag M, Balu R, Phillips E, et al. High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients. Clin Infect Dis. 2008;46(7):1111–1118. doi: 10.1086/529382. [DOI] [PubMed] [Google Scholar]
  • 19.Mallal S, Nolan D, Witt C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002;359(9308):727–732. doi: 10.1016/s0140-6736(02)07873-x. [DOI] [PubMed] [Google Scholar]
  • 20.Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450 2D6 Genotype and Codeine Therapy: 2014 Update. Clin Pharmacol Ther. 2014 doi: 10.1038/clpt.2013.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Kelly PA. Pharmacogenomics: why standard codeine doses can have serious toxicities or no therapeutic effect. Oncol Nurs Forum. 2013;40(4):322–324. doi: 10.1188/13.ONF.322-324. [DOI] [PubMed] [Google Scholar]
  • 22.Prows CA, Zhang X, Huth MM, et al. Codeine-related adverse drug reactions in children following tonsillectomy: A prospective study. Laryngoscope. 2013 doi: 10.1002/lary.24455. [DOI] [PubMed] [Google Scholar]
  • 23.Anderson JL, Horne BD, Stevens SM, et al. A randomized and clinical effectiveness trial comparing two pharmacogenetic algorithms and standard care for individualizing warfarin dosing (CoumaGen-II) Circulation. 2012;125(16):1997–2005. doi: 10.1161/CIRCULATIONAHA.111.070920. [DOI] [PubMed] [Google Scholar]
  • 24.Pirmohamed M, Burnside G, Eriksson N, et al. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013;369(24):2294–2303. doi: 10.1056/NEJMoa1311386. [DOI] [PubMed] [Google Scholar]
  • 25.Kimmel SE, French B, Kasner SE, et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013;369(24):2283–2293. doi: 10.1056/NEJMoa1310669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Weitzel KW, Elsey AR, Langaee TY, et al. Clinical pharmacogenetics implementation: Approaches, successes, and challenges. Am J Med Genet C. 2014;166(1):56–67. doi: 10.1002/ajmg.c.31390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Haga SB, Moaddeb J. Comparison of delivery strategies for pharmacogenetic testing services. Pharmacogenetics and genomics. 2014;24(3):139–145. doi: 10.1097/FPC.0000000000000028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Hoffman JM, Haidar CE, Wilkinson MR, et al. PG4KDS: A model for the clinical implementation of pre-emptive pharmacogenetics. Am J Med Genet C. 2014;166(1):45–55. doi: 10.1002/ajmg.c.31391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Gamazon ER, Skol AD, Perera MA. The limits of genome-wide methods for pharmacogenomic testing. Pharmacogenetics and genomics. 2012;22(4):261–272. doi: 10.1097/FPC.0b013e328350ca5f. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Thomas RE, Chau SB. The AmpliChip: A review of its analytic and clinical validity and clinical utility. Curr Drug Saf. 2014 doi: 10.2174/1574886309666140428121036. [DOI] [PubMed] [Google Scholar]
  • 31.Ma JD, Lee KC, Kuo GM. Clinical application of pharmacogenomics. J Pharm Pract. 2012;25(4):417–427. doi: 10.1177/0897190012448309. [DOI] [PubMed] [Google Scholar]
  • 32.Scott SA. Clinical pharmacogenomics: opportunities and challenges at point of care. Clinical pharmacology and therapeutics. 2013;93(1):33–35. doi: 10.1038/clpt.2012.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Beatty SJ, McCormick KM, Beale DJ, et al. Current trends in outpatient pharmacy services and billing. J Am Pharm Assoc. 2012;52(2):154–160. doi: 10.1331/JAPhA.2012.11213. [DOI] [PubMed] [Google Scholar]
  • 34.Bailey JE, Pope RA, Elliott EC, Wan JY, Waters TM, Frisse ME. Health information exchange reduces repeated diagnostic imaging for back pain. Ann Emerg Med. 2013;62(1):16–24. doi: 10.1016/j.annemergmed.2013.01.006. [DOI] [PubMed] [Google Scholar]
  • 35.Bailey JE, Wan JY, Mabry LM, et al. Does health information exchange reduce unnecessary neuroimaging and improve quality of headache care in the emergency department? Journal of general internal medicine. 2013;28(2):176–183. doi: 10.1007/s11606-012-2092-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Witry MJ, Doucette WR. Obtaining patient test results from clinical laboratories: a survey of state law for pharmacists. J Am Pharm Assoc. 2009;49(3):423–426. doi: 10.1331/JAPhA.2009.08049. [DOI] [PubMed] [Google Scholar]
  • 37.Dimitropoulos L, Patel V, Scheffler SA, Posnack S. Public attitudes toward health information exchange: perceived benefits and concerns. Am J Manag Care. 2011;17(12 Spec No):SP111–116. [PubMed] [Google Scholar]
  • 38.O’Donnell HC, Patel V, Kern LM, et al. Healthcare consumers’ attitudes towards physician and personal use of health information exchange. Journal of general internal medicine. 2011;26(9):1019–1026. doi: 10.1007/s11606-011-1733-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.McKnight AG, Thomason AR. Pharmacists’ advancing roles in drug and disease management: a review of states’ legislation. J Am Pharm Assoc. 2009;49(4):554–558. doi: 10.1331/JAPhA.2009.08056. [DOI] [PubMed] [Google Scholar]
  • 40.Punekar Y, Lin SW, Thomas J., 3rd Progress of pharmacist collaborative practice: status of state laws and regulations and perceived impact of collaborative practice. J Am Pharm Assoc. 2003;43(4):503–510. doi: 10.1331/154434503322226257. [DOI] [PubMed] [Google Scholar]
  • 41.Weaver K. Collaborative practice agreements vary among the states. American Pharmacists Association; 2013. [Accessed on April 14, 2014]. [Google Scholar]
  • 42.Albanese NP, Rouse MJ. Scope of contemporary pharmacy practice: roles, responsibilities, and functions of pharmacists and pharmacy technicians. J Am Pharm Assoc. 2010;50(2):e35–69. doi: 10.1331/JAPhA.2010.10510. [DOI] [PubMed] [Google Scholar]
  • 43.Zingone MM, Malcolm KE, McCormick SW, Bledsoe KR. Analysis of pharmacist charges for medication therapy management services in an outpatient setting. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2007;64(17):1827–1831. doi: 10.2146/ajhp060438. [DOI] [PubMed] [Google Scholar]
  • 44.Christensen DB, Roth M, Trygstad T, Byrd J. Evaluation of a pilot medication therapy management project within the North Carolina State Health Plan. J Am Pharm Assoc. 2007;47(4):471–483. doi: 10.1331/JAPhA.2007.06111. [DOI] [PubMed] [Google Scholar]
  • 45.Sound Medication Therapy Management Programs, Version 2.0 with validation study. J Manag Care Pharm. 2008;14(1 Suppl B):S2–44. [PubMed] [Google Scholar]
  • 46.Moczygemba LR, Barner JC, Lawson KA, et al. Impact of telephone medication therapy management on medication and health-related problems, medication adherence, and Medicare Part D drug costs: a 6-month follow up. Am J Geriatr Pharmac. 2011;9(5):328–338. doi: 10.1016/j.amjopharm.2011.08.001. [DOI] [PubMed] [Google Scholar]
  • 47.Hassan S, Naboush A, Radbel J, et al. Telephone-based anticoagulation management in the homebound setting: a retrospective observational study. Int J Gen Med. 2013;6:869–875. doi: 10.2147/IJGM.S50057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Lau DT, Stubbings J. Medicare part D research and policy highlights, 2012: impact and insights. Clin Ther. 2012;34(4):904–914. doi: 10.1016/j.clinthera.2012.02.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Moczygemba LR, Barner JC, Brown CM, et al. Patient satisfaction with a pharmacist-provided telephone medication therapy management program. Res Social Adm Pharm. 2010;6(2):143–154. doi: 10.1016/j.sapharm.2010.03.005. [DOI] [PubMed] [Google Scholar]
  • 50.Schiff GD, Klass D, Peterson J, Shah G, Bates DW. Linking laboratory and pharmacy: opportunities for reducing errors and improving care. Archives of internal medicine. 2003;163(8):893–900. doi: 10.1001/archinte.163.8.893. [DOI] [PubMed] [Google Scholar]
  • 51.McMahan R. Operationalizing MTM through the use of health information technology. Journal of managed care pharmacy : JMCP. 2008;14(2):S18–S21. [PubMed] [Google Scholar]
  • 52.Lauffenburger JC, Balasubramanian A, Farley JF, et al. Completeness of prescription information in US commercial claims databases. Pharmacoepidemiol Drug Saf. 2013;22(8):899–906. doi: 10.1002/pds.3458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Hicks JK, Crews KR, Hoffman JM, et al. A clinician-driven automated system for integration of pharmacogenetic interpretations into an electronic medical record. Clinical pharmacology and therapeutics. 2012;92(5):563–566. doi: 10.1038/clpt.2012.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.BLS. Pharmacist: Occupational Outlook Handbook. U.S. Bureau of Labor Statistics; 2014. [Accessed March 13, 2014]. http://www.bls.gov/ooh/healthcare/pharmacists.htm. [Google Scholar]
  • 55.Blake KB, Madhavan SS. Perceived barriers to provision of medication therapy management services (MTMS) and the likelihood of a pharmacist to work in a pharmacy that provides MTMS. The Annals of pharmacotherapy. 2010;44(3):424–431. doi: 10.1345/aph.1M386. [DOI] [PubMed] [Google Scholar]
  • 56.ACPE. Accreditation standards and guidelines for the Professional Program in Pharmacy leading to the Doctor of Pharmacy Degree. Accreditation Council for Pharmacy Education; 2006. https://www.acpe-accredit.org/pdf/ACPE_Revised_PharmD_Standards_Adopted_Jan152006.pdf. [Google Scholar]
  • 57.Battaglia JN, Kieser MA, Bruskiewitz RH, Pitterle ME, Thorpe JM. An online virtual-patient program to teach pharmacists and pharmacy students how to provide diabetes-specific medication therapy management. American journal of pharmaceutical education. 2012;76(7) doi: 10.5688/ajpe767131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Begley KJ, Coover KL, Tilleman JA, Haddad AMR, Augustine SC. Medication therapy management training using case studies and the MirixaPro platform. American journal of pharmaceutical education. 2011;75(3) doi: 10.5688/ajpe75349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Eukel HN, Skoy ET, Frenzel JE. Provision of medication therapy management to university faculty and staff members by third-year pharmacy students. American journal of pharmaceutical education. 2010;74(10) doi: 10.5688/aj7410182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Ryder PT, Meyerson BE, Coy KC, von Hippel CD. Pharmacists’ perspectives on HIV testing in community pharmacies. J Am Pharm Assoc. 2013;53(6):595–600. doi: 10.1331/JAPhA.2013.12240. [DOI] [PubMed] [Google Scholar]
  • 61.Moczygemba LR, Goode JV, Silvester JA, Matzke GR. Pharmacy practice in Virginia in 2011. The Annals of pharmacotherapy. 2012;46(4):S13–26. doi: 10.1345/aph.1Q802. [DOI] [PubMed] [Google Scholar]
  • 62.McCullough KB, Formea CM, Berg KD, et al. Assessment of the pharmacogenomics educational needs of pharmacists. American journal of pharmaceutical education. 2011;75(3):51. doi: 10.5688/ajpe75351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Murphy JE, Green JS, Adams LA, Squire RB, Kuo GM, McKay A. Pharmacogenomics in the curricula of colleges and schools of pharmacy in the United States. American journal of pharmaceutical education. 2010;74(1):7. doi: 10.5688/aj740107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Krynetskiy E, Lee Calligaro I. Introducing pharmacy students to pharmacogenomic analysis. American journal of pharmaceutical education. 2009;73(4):71. doi: 10.5688/aj730471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Lee KC, Ma JD, Hudmon KS, Kuo GM. A train-the-trainer approach to a shared pharmacogenomics curriculum for US colleges and schools of pharmacy. American journal of pharmaceutical education. 2012;76(10):193. doi: 10.5688/ajpe7610193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Drozda K, Labinov Y, Jiang R, et al. A pharmacogenetics service experience for pharmacy students, residents, and fellows. American journal of pharmaceutical education. 2013;77(8):175. doi: 10.5688/ajpe778175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Formea CM, Nicholson WT, McCullough KB, et al. Development and evaluation of a pharmacogenomics educational program for pharmacists. American journal of pharmaceutical education. 2013;77(1):10. doi: 10.5688/ajpe77110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Haga SB, Burke W, Ginsburg GS, Mills R, Agans R. Primary care physicians’ knowledge of and experience with pharmacogenetic testing. Clinical genetics. 2012;82(4):388–394. doi: 10.1111/j.1399-0004.2012.01908.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Selkirk CG, Weissman SM, Anderson A, Hulick PJ. Physicians’ preparedness for integration of genomic and pharmacogenetic testing into practice within a major healthcare system. Genetic testing and molecular biomarkers. 2013;17(3):219–225. doi: 10.1089/gtmb.2012.0165. [DOI] [PubMed] [Google Scholar]
  • 70.Stanek EJ, Sanders CL, Taber KA, et al. Adoption of pharmacogenomic testing by US physicians: results of a nationwide survey. Clinical pharmacology and therapeutics. 2012;91(3):450–458. doi: 10.1038/clpt.2011.306. [DOI] [PubMed] [Google Scholar]
  • 71.Green JS, O’Brien TJ, Chiappinelli VA, Harralson AF. Pharmacogenomics instruction in US and Canadian medical schools: implications for personalized medicine. Pharmacogenomics. 2010;11(9):1331–1340. doi: 10.2217/pgs.10.122. [DOI] [PubMed] [Google Scholar]
  • 72.AACN. The essentials of baccalaureate education for professional nursing practice. Washington, DC: American Association of Colleges of Nursing; 2008. http://www.aacn.nche.edu/Education/pdf/BaccEssentials08.pdf. [Google Scholar]
  • 73.Greco KE, Tinley S, Seibert D. Essential genetic and genomic competencies for nurses with graduate degrees. Silver Spring, MD: American Nurses Association and International Society of Nurses in Genetics; 2012. [Google Scholar]
  • 74.Jenkins JF, Calzone K. Essentials of genetic and genomic nursing: competencies, curricula guidelines, and outcome indicators. 2. Silver Spring, MD: American Nurses Association; 2008. [Google Scholar]
  • 75.Thompson HJ, Brooks MV. Genetics and genomics in nursing: evaluating Essentials implementation. Nurse education today. 2011;31(6):623–627. doi: 10.1016/j.nedt.2010.10.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Evans BJ. Finding a liability-free space in which personalized medicine can bloom. Clinical pharmacology and therapeutics. 2007;82(4):461–465. doi: 10.1038/sj.clpt.6100335. [DOI] [PubMed] [Google Scholar]
  • 77.Prebula RJ. The promise of personalized medicine: regulatory controls and tort influences in the context of personalized risks and benefits. The Journal of contemporary health law and policy. 2010;26(2):343–372. [PubMed] [Google Scholar]
  • 78.Moore JJ, Matlock AG. Shared liability? Consultants, pharmacists, and the emergency physician: legal cases and caveats. The Journal of emergency medicine. 2014;46(5):612–616. doi: 10.1016/j.jemermed.2013.08.035. [DOI] [PubMed] [Google Scholar]
  • 79.Hornish ML. Just what the doctor ordered - or was it?: Missouri pharmacists’ duty of care in the 21st century. Missouri Law Rev. 2000;65(1075):1085. [Google Scholar]
  • 80.Zierler-Brown S, Brown TR, Chen D, Blackburn RW. Clinical documentation for patient care: models, concepts, and liability considerations for pharmacists. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2007;64(17):1851–1858. doi: 10.2146/ajhp060682. [DOI] [PubMed] [Google Scholar]
  • 81.Donovan MJ. Legal issues stemming from the advancement of pharmacogenomics. [Accessed March 25, 2013];UCLA Journal of Law & Technology. 2010 14(1):35. http://www.lawtechjournal.com/articles/2010/01_100915_donovan.pdf. [Google Scholar]
  • 82.Lounsbery JL, Green CG, Bennett MS, Pedersen CA. Evaluation of pharmacists’ barriers to the implementation of medication therapy management services. J Am Pharm Assoc. 2009;49(1):51–U54. doi: 10.1331/JAPhA.2009.017158. [DOI] [PubMed] [Google Scholar]
  • 83.Moczygemba LR, Barner JC, Gabrillo ER, Godley PJ. Development and implementation of a telephone medication therapy management program for Medicare beneficiaries. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2008;65(17):1655–1660. doi: 10.2146/ajhp070639. [DOI] [PubMed] [Google Scholar]
  • 84.Law AV, Okamoto MP, Brock K. Ready, willing, and able to provide MTM services?: A survey of community pharmacists in the USA. Res Social Adm Pharm. 2009;5(4):376–381. doi: 10.1016/j.sapharm.2009.01.001. [DOI] [PubMed] [Google Scholar]
  • 85.Lloyd KB, Evans RL. Reimbursement model for pharmacist-directed medication therapy management. J Am Pharm Assoc. 2012;52(2):161–169. doi: 10.1331/JAPhA.2012.11228. [DOI] [PubMed] [Google Scholar]
  • 86.Trapskin K, Johnson C, Cory P, Sorum S, Decker C. Forging a novel provider and payer partnership in Wisconsin to compensate pharmacists for quality-driven pharmacy and medication therapy management services. J Am Pharm Assoc. 2009;49(5):642–651. doi: 10.1331/JAPhA.2009.08158. [DOI] [PubMed] [Google Scholar]
  • 87.Scott MA, Hitch WJ, Wilson CG, Lugo AM. Billing for pharmacists’ cognitive services in physicians’ offices: multiple methods of reimbursement. J Am Pharm Assoc. 2012;52(2):175–180. doi: 10.1331/JAPhA.2012.11218. [DOI] [PubMed] [Google Scholar]
  • 88.Traynor K. CMS chief affirms incident-to billing for pharmacists is allowed. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2014;71(12):977–978. doi: 10.2146/news140042. [DOI] [PubMed] [Google Scholar]
  • 89.Boyd ST, Boyd LC, Zillich AJ. Medication therapy management survey of the prescription drug plans. J Am Pharm Assoc. 2006;46(6):692–699. doi: 10.1331/1544-3191.46.6.692.boyd. [DOI] [PubMed] [Google Scholar]
  • 90.Watkins JL, Landgraf A, Barnett CM, Michaud L. Evaluation of pharmacist-provided medication therapy management services in an oncology ambulatory setting. J Am Pharm Assoc. 2012;52(2):170–174. doi: 10.1331/JAPhA.2012.11171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Albada A, van Dulmen S, Bensing JM, Ausems MG. Effects of a pre-visit educational website on information recall and needs fulfilment in breast cancer genetic counselling, a randomized controlled trial. Breast Cancer Res. 2012;14(2):R37. doi: 10.1186/bcr3133. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  • 92.Zhang S, Doucette WR, Urmie JM, Xie Y, Brooks JM. Factors associated with independent pharmacy owners’ satisfaction with Medicare Part D contracts. Res Social Adm Pharm. 2010;6(2):121–129. doi: 10.1016/j.sapharm.2010.03.004. [DOI] [PubMed] [Google Scholar]

RESOURCES