Pharmacogenomic Testing to Support Prescribing in Primary Care: a Structured Review of Implementation Models

Figures & data

Figure 1. Study selection process to determine papers describing implementation models for PGx via panel testing within primary care.

Table 1. Summary of implementation models characteristics: recruitment strategy, patient eligibility, PGx testing strategy, PGx panel, lead practitioner, supporting practitioners, modality of results delivery, outcomes.

Implementation model characteristics	Dressler et al.	Dunnenberger et al.	Schwartz et al.	Haga et al.	Dawes et al.	Papastergiou et al.	Bank et al.	Van der Wouden et al.
Year	2016–2017	2015	2016	2012–2013	2015	Not stated	2014–2016	2018
Country	USA	USA	USA	USA	Canada	Canada	The Netherlands	The Netherlands
Recruitment strategy and setting	Recruitment by PCP	Recruitment by PCP into hospital setting, subsequently direct patient access from home	Research pharmacist within primary healthcare practice	In-practice pharmacist or PCP in 2 primary healthcare practices	PCP and community pharmacist in 5 primary healthcare practices and 1 community pharmacy	Community pharmacist in community pharmacy setting	Pharmacist in primary healthcare practice	Community pharmacist with previous PGx research training in primary healthcare practice
Patient eligibility	Pre-emptive testing: >65 yoa, Medicare insurance, 4 or more prescription drugs, at least one actionable GDI (as per CPIC guidelines)	Pre-emptive testing: no exclusions	Pre-emptive testing: patients prescribed 7 or more medications	Reactive testing after prescription of a listed medication.	Pre-emptive testing of patients with a specific chronic condition	Reactive testing: >18 yoa, 1 or more medications linked to known pharmacogenomic variant, in response to reduced effectiveness, ADR, or initiation of medication	Reactive testing: incident prescription of a listed medication	Reactive testing: initiation of a listed medication with DPWG recommendations
PGx strategy: pre-test counseling and sampling	PCP-led. Buccal sample	2 phase strategy: multi-disciplinary clinic comprising clinical geneticist, genetic counselor and pharmacist Direct access testing via home swab and on-line patient information	Pharmacist-led, buccal sample	2 approaches: PCP-led with pharmacy support, and in-house pharmacist-led with PCP support. Buccal sample	PCP-led: buccal sample	Pharmacist-led: buccal sample	Pharmacist-led: buccal sample	Pharmacist-led: buccal sample
Panel choice: number of variants and genes	Variants within 16 genes: 56 linked medications	Multi-gene panel (no further details)	Variants within 14 genes	Variants within 6 genes: 12 linked medications.	24 variants within 7 genes: 24 linked medications.	Variants within 10 genes: >100 linked medications	Variants within 8 genes	Variants within 12 genes
Medication classes included	Antidepressant, antipsychotic, analgesic, antigout, anticoagulant, anticonvulsant, anti-HIV, antineoplastic, cardiovascular (clopidogrel, statins) immunosuppressant, proton pump inhibitor, tamoxifen	No selection or limitation	Not stated	Antidepressant, anticoagulant, anticonvulsant, analgesic, cardiovascular (beta-blocker, clopidogrel, statins) proton pump inhibitor	Antidepressant, anticoagulant, antigout, analgesic, cardiovascular (beta-blocker, statins), proton pump inhibitor	Antidepressant anticoagulant analgesic cardiovascular (clopidogrel, statins), proton pump inhibitor	Antidepressant, cardiovascular (statins)	Antibiotic, antidepressant, antipsychotic, antineoplastic, analgesic cardiovascular (beta-blocker, clopidogrel, flecainide and statins) immunosuppressants, tamoxifen
Lead practitioner	PCP recruited patients and gave results	First multi-disciplinary clinic comprising clinical geneticist, genetic counselor and pharmacist. Subsequently PCP	Research pharmacist	Comparison of PCP-led with pharmacy support, and in-house pharmacist-led with PCP support	PCP and community pharmacist	Community pharmacist	Community pharmacist	Community Pharmacist
Supporting practitioners/expert advice	Pharmacist generated summary of PGxresults, concurrent medication and recommendations for medication management	Genetic counselor, ANP and pharmacist supported in taking family history and giving results	PCP and expert advisory group comprising pharmacists with PGx experience	Comparison of PCP-led with pharmacy support, and in-house pharmacist-led with PCP support				PCP
Modality of results delivery	Pharmacist generated summary utilized within PCP consultation	Clinical summary sent to patients and lead practitioner for use within results consultation: firstly clinical genetics service appointment, subsequently PCP consultation	MTM-plus consult: Summary and recommendations based on CDSS comprising PGx and other patient data, and on advice from expert group. Sent to PCP. Accepted medication changes communicated to patient by PCP Gene card containing PGx results sent to patient and PCP	Drug-specific brochures supported communication of results to patients at PCP discretion	Consultation utilizing Condition-based CDSS comprising PGx and other patient data: guideline-linked summary and recommendation Direct use of MDSS within consultation	Report summarizing Pgx data with CPIC guideline and FDA-linked recommendations	Report summarizing PGx data with DPWG-linked recommendations	Actionable results send to requesting pharmacist: results fed back patients +/− PCP at pharmacist discretion
Primary outcomes	Physician knowledge and barriers; pre- and post-test survey, and phone interviews Patient understanding: pre- and post-test surveys		Proof of feasibility of clinical pharmacist-led MTM Plus service Identification of ‘medication-related problems’ which comprised interactions and potential ADRs	Effectiveness: tests ordered, medication or dosage changes, ADR Change in PCP attitudes, knowledge and experience Patient attitudes and beliefs Costs: pharmacist consultation time, medication changes	Feasibility of obtaining genotype from buccal samples Ability to link results to MDSS utilization of MDSS	Feasibility of community-pharmacist-led PGx testing. Acceptance rate of recommendations by physicians	Feasibility of pharmacist-initiated pPGx testing in primary care Frequency of actionable genotypes, frequency of incident prescriptions, number of patients with actionable gene-drug pair, drug-related interventions, pharmacy visits, drug dose	Investigate shared decision-making, reporting of results to patients and time Identification of remaining implementation barriers and enablers

CDSS: Clinical decision support system; CPIC: Clinical Pharmacogenetics Implementation Consortium; DPWG: Dutch Pharmacogenetics Working Group; GDI: Drug–gene interaction; MDSS: Medication Delivery Support System; PCP: Primary care physician; PGx: Pharmacogenomic.

Data taken from [20–32].

Table 2. Summary of results: key barriers and challenges, key enablers and solutions.

Themes	Barriers and challenges	Enablers and potential solutions	Ref.
Pre-test counseling and consent	Practitioner time Patient time Lack of reimbursement Attendance at appointment within clinical genetics clinic Family-history taking Non-prescribing practitioners taking medication history	Condensed family history limited to 2 questions Pre-testing information for patients	[22,25,30,32]
Practitioner knowledge and education	PCP attendance at educational sessions Delivery of educational sessions at multiple geographical sites Lack of PCP knowledge Lack of pharmacist knowledge	Participation in delivering PGx testing in context of study Pilot phase for implementation PCPs undergoing PGx testing themselves On-demand educational material Education in combination of formats (face-to-face, on-line) Addressing specific educational needs (e.g. report interpretation, counseling) Creation of ‘champions’ PCP perception of value and utility of PGx testing	[20–23,27,32]
PGx testing	Inability to request PGx testing via EMR Lack of established eligibility criteria Turnaround times (7–23 days) Lack of reimbursement for pharmacist time Cost to patient Cost to medical insurer Buccal sample: patient administered at home	PGx testing via buccal samples: PCP or pharmacist-administered	[20,23,25,27–30,32]
Role of the pharmacist	PCP-initiated testing with access of practitioners to on-call pharmacy support only	Pharmacist-initiated PGx testing In-house or MDT Pharmacy support Recording PGx data in EMR Formulation of summaries Pharmacist-led medication review / MTM consultation	[20–22,25–27,29–32]
Recording of PGx data	Lack of IT infrastructure Patient concerns re data governance and privacy Time taken to record PGx data in EMR Lack of reimbursement for time	Direct integration of PGx data into EMR Recording of PGx data in EMR by pharmacist	[20,23,25,27,31,32]
Decision support	PCP confidence in interpretation of PGx results and reports Time constraints Managing patient expectations Lack of guidance Lack of interoperability between EHR and CDSS	Clinical summary comprising PGx data, medications and recommendations for medication management. Linkage of PGx data to guidance Shared decision-making involving PCPs and pharmacist Electronic CDSS Condition-based MDSS	[20,23,25,28,31,32]
Clinical utility: translation of recommendations into medication changes	Lack of access by PCP to pharmacist advice PCP lack of understanding of applicability Non-integration into clinical workflow	Recommendations made by Community pharmacist Recommendations reviewed within Medication review or MTM consultation	[20,25,29,30]
Clinical utility (other)	Lack of evidence for cost–effectiveness	Prevalence of PGx variants Prevalence of actionable variants (variants with concurrent prescription of relevant medication) ‘Re-use’ of PGx data in aiding prescribing decisions Patient autonomy Improving concordance Reassurance regarding medication decisions Explanation of previous medication experiences or ADR	[20,23–25,27–32]

ADR: Adverse drug reaction; CDSS: Clinical decision support system; EMR: Electronic medical record; MDSS: Medication-decision support system; MDT: Multi-disciplinary team; MTM: Medicines therapy management; PCP: Primary care practitioner/GP; PGx: Pharmacogenomic.

Table 3. Frameworks for implementation of genomic and non-genomic interventions into clinical care: domains and priorities mapped against implementation issues for PGx and potential enablers.

IGNITE Framework Domain: High Priority Construct	Integrating Primary and Specialist Healthcare in the UK	Issues identified for consideration of implementation of PGx into Primary Care in the UK	Existing infrastructure and other potential enablers
Inner setting: Implementation climate (reason, priority, organizational incentives, goals, learning climate)	Organizational buy-in Existing national transformational programs, mechanisms and collaborations		National commissioning and strategic infrastructure: nationalized state-funded NHS, NHS Genomic Medicine Service and GLH, Genomic Test Directory, Health Education England Genomics Education Program, National Workforce Steering Groups Nationally commissioned SMR in primary care setting
Inner setting: Implementation readiness (leadership/engagement, resources, access to knowledge and information)	Clinical leadership Workforce planning: knowledge and skills, definition of roles and responsibilities	Championing and expert advice role of PCPs or pharmacists with experience in PGx testing Need for clear infrastructure and pathway Define roles and responsibilities within Primary Care Team: pharmacists able and motivated to play a key role in leadership and in implementation within the Primary Care setting, with PCP and expert advice and support Development of CDSS: Recognition of CDSS as resource for awareness and education	PCPs and pharmacists in championing roles within national strategic and commissioning structures (NHSE, HEE GEP, RCGP) PCPs and pharmacists with additional genomic expertise (e.g. MSc in Genomic Medicine, Consultant Pharmacist model) Engagement of national representative bodies (RCGP, RPS) Collaboration of PCPs and pharmacists within these structures to establish pathways, roles and responsibilities Establishment of local and regional championing roles: for PCPs and pharmacists. British National FormularyNon-pharmacogenomics evidence-based CDSS implemented within routine NHS clinical care
Individuals‘ characteristics: Knowledge and beliefs about the intervention Self-efficacy	Education: knowledge and skills Working together: mechanisms for collaborative working and sharing knowledge, access to expert advice	Belief of PCP and pharmacists that PGx will be of value Collaborative working within the Primary Care Team, specifically prescribing practitioners and pharmacists Knowledge and resources linked to CDSS and PGx results; with mixed format CME to support	Existing multi-disciplinary working structures within Primary Care: pharmacists and PCPs already and increasingly work closely in multi-disciplinary structure National, regional and local championing roles HEE GEP to support development of educational resources, both point-of-care and other formats
Intervention characteristics: Relative advantage	Model of care: Based on evidence and guidelines Defined roles and responsibilities Commissioning arrangements	PGx testing with early evidence for clinical utility Identification of eligibility criteria for testing Process for requesting PGx testing directly from EMR or electronic platform Turnaround time Commissioning arrangements and cost–effectiveness	National research bodies promoting and supporting PGx research within Primary care Genomic Test Directory, Pharmacogenomics Genomics Clinical Interpretation Partnership and Pharmacogenomics Testing Working Group establishing national eligibility criteria and evidence-based PGx testing gene-panel NGIS National commissioning infrastructure
Intervention characteristics: Cost	Model of care: appropriately resourced	Adequate time for consent, testing, entry of patient information in EMR and for giving results and SMR Appropriate reimbursement	Continued generation of evidence for cost–effectiveness through research programs Establish commissioning infrastructure and accountability, aligning with existing NHS strategy and national primary care commissioning arrangements
Process: Engaging (opinion leaders, implementation leaders, champions)	Clinical leadership and champions	Championing and expert advice role of PCPs or pharmacists with experience in PGx testing	Establishment of local, regional and national network of champions PCPs and pharmacists in existing championing roles within national infrastructure (NHSE, RCGP, BPS, RPS, HEE GEP)
Process: Executing	Appropriately resourced Operational procedures: frameworks and adequately funded Stakeholder buy-in Shared guidelines and protocols Exchange of patient information on EMR Working together: mechanisms for collaborative working and sharing knowledge, access to expert advice	Adequate time for consent, testing, entry of patient information in EMR and forgiving results and SMR Appropriate reimbursement Consensus consent framework for PGx testing Pathway for recording patient information within EMR CDSS with embedded guidelines, clinically actionable recommendations	National commissioning structure: aligning with SMR Existing HEE GEP Competency Frameworks (e.g. consent for genomic testing): development of PGx-specific competency frameworks National IT infrastructure: collaboration between this and primary care IT providers Resources and training for all responsible for coding (clinical and admin roles) Existing nationalized infrastructure
Process: Reflecting and evaluating	Monitoring processes and outcomes
Patient characteristics	Patient-centered characteristics	Time taken and process for consent

CDSS: Clinical decision support system; CME: Continuing medical education; GLH: Genomic Laboratory Hub; HEE GEP: Health Education England Genomics Education Programme; IGNITE: Implementing GeNomics In PracTicE; NGIS: National Genomic Information System; NHS: National Health Service; PCP: Primary care practitioner; RCGP: Royal College General Practitioners; RPS: Royal Pharmaceutical Society; SMR: Structured medication review.

Data taken from [17,18].

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