Implementation of Pharmacogenetics in Primary Care: A Multi-Stakeholder Perspective

Introduction Aberrant pharmacogenetic variants occur in a high proportion of people and might be relevant for the prescription of over 26 drugs in primary care. Early identification of patients who metabolize these drugs more rapidly or slowly than average could predict therapeutic effectivity and safety. Yet implementation of pharmacogenetics is progressing slowly. A high public health impact can potentially be achieved by increasing the proportion of people tested, when and where eligible according to clinical validity and utility. Methods In this study we defined actions, roles, and responsibilities for implementation of pharmacogenetics in primary care in consultation with stakeholder groups, by using a three-step mixed-methods approach. First, to define barriers and facilitators, public pharmacists (n = 24), primary care physicians (n = 8), and patients (n = 21) participated in focus groups and face-to-face interviews. Second, a multidisciplinary expert meeting (n = 16) was organized to define desired actions, roles, and responsibilities. Third, an online Delphi Study (n = 18) was conducted to prioritize the designated actions. Results For the integration of pharmacogenetics in primary care guidelines and practice, lack of evidence for clinical utility was mentioned as a main barrier. Furthermore, reimbursement, and facilitation of data registration and sharing were considered as key elements for future routine application of pharmacogenetic testing. Moreover, the division of roles and responsibilities, especially between general practitioners and pharmacists, is currently perceived as unclear. Sixteen actions in these four areas (clinical utility, reimbursement, data registration and sharing, and roles and responsibilities) were formulated and assigned to specific actors during the expert meeting. After ranking these 16 actions in the Delphi Study, nine actions remained pertinent, covering the four areas with at least one action. However, participants showed low agreement on the prioritization of the different actions, illustrating their different perspectives and the need to attune between them. Discussion Stakeholders together were able to formulate required actions to achieve true integration of pharmacogenetics in primary care, but no consensus could be achieved on the prioritization of the actions. Coordination of the current independent initiatives by the different stakeholders could facilitate effective and efficient implementation of useful pharmacogenetics in primary care.

[1]  R. Altman,et al.  Pharmacogenomics: will the promise be fulfilled? , 2011, Nature Reviews Genetics.

[2]  W. Rodenburg,et al.  Review of the Reported Measures of Clinical Validity and Clinical Utility as Arguments for the Implementation of Pharmacogenetic Testing: A Case Study of Statin-Induced Muscle Toxicity , 2017, Front. Pharmacol..

[3]  Charis Eng,et al.  Implementation of Clinical Pharmacogenomics within a Large Health System: From Electronic Health Record Decision Support to Consultation Services , 2016, Pharmacotherapy.

[4]  C. Vleuten,et al.  Prioritization of future genetics education for general practitioners: a Delphi study , 2012, Genetics in Medicine.

[5]  F. Geels Technological transitions as evolutionary reconfiguration processes: a multi-level perspective and a case-study , 2002 .

[6]  N. Dalkey,et al.  An Experimental Application of the Delphi Method to the Use of Experts , 1963 .

[7]  Teri E Klein,et al.  Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers. , 2015, Annual review of pharmacology and toxicology.

[8]  H. Guchelaar,et al.  Just how feasible is pharmacogenetic testing in the primary healthcare setting? , 2012, Pharmacogenomics.

[9]  Chia-Chien Hsu,et al.  The Delphi Technique: Making Sense of Consensus , 2007 .

[10]  W. Burke,et al.  Pharmacogenetic testing: not as simple as it seems , 2008, Genetics in Medicine.

[11]  D. Gurwitz,et al.  Assessment of pharmacogenetic tests: presenting measures of clinical validity and potential population impact in association studies , 2016, The Pharmacogenomics Journal.

[12]  Janet E Olson,et al.  Integrating Pharmacogenomics into Clinical Practice: Promise vs Reality. , 2016, The American journal of medicine.

[13]  E. M. Vos,et al.  Stakeholder perspectives on the implementation of genetic carrier screening in a changing landscape , 2017, BMC Health Services Research.

[14]  M O Karlsson,et al.  Implementing Pharmacogenomics in Europe: Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium , 2017, Clinical pharmacology and therapeutics.

[15]  D. Voora,et al.  Delivering pharmacogenetic testing in a primary care setting , 2013, Pharmacogenomics and personalized medicine.

[16]  Jennifer Abbasí Getting Pharmacogenomics Into the Clinic. , 2016, JAMA.

[17]  Gillian Bartlett,et al.  Pharmacogenomics in Primary Care: A Crucial Entry Point for Global Personalized Medicine? , 2012, Current pharmacogenomics and personalized medicine.

[18]  Kelly L. Scolaro,et al.  Transitioning Pharmacogenomics into the Clinical Setting: Training Future Pharmacists , 2016, Front. Pharmacol..

[19]  Jan Rotmans,et al.  Towards transition management of European water resources , 2006 .

[20]  A. Shuldiner,et al.  Educational innovations in clinical pharmacogenomics , 2016, Clinical pharmacology and therapeutics.

[21]  T. Doksum,et al.  Integrating Molecular Medicine into the US Health‐care System: Opportunities, Barriers, and Policy Challenges , 2007, Clinical pharmacology and therapeutics.

[22]  J. Broerse,et al.  Developing a framework for implementation of genetic services: learning from examples of testing for monogenic forms of common diseases , 2014, Journal of Community Genetics.

[23]  F. Geels,et al.  Typology of sociotechnical transition pathways , 2007 .

[24]  Y. Teo,et al.  Role of pharmacogenetics in public health and clinical health care: a SWOT analysis , 2016, European Journal of Human Genetics.

[25]  J. Stingl,et al.  Medical education in pharmacogenomics—results from a survey on pharmacogenetic knowledge in healthcare professionals within the European pharmacogenomics clinical implementation project Ubiquitous Pharmacogenomics (U-PGx) , 2017, European Journal of Clinical Pharmacology.

[26]  F. Asselbergs,et al.  Use of Pharmacogenetic Drugs by the Dutch Population , 2019, Front. Genet..

[27]  Erica A. Bowton,et al.  Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing , 2013, Clinical pharmacology and therapeutics.

[28]  R. Verbrugge,et al.  Adoption of Pharmacogenomic Testing by US Physicians: Results of a Nationwide Survey , 2012, Clinical pharmacology and therapeutics.

[29]  M. Wagner,et al.  The IGNITE Pharmacogenetics Working Group: An Opportunity for Building Evidence with Pharmacogenetic Implementation in a Real‐World Setting , 2017, Clinical and translational science.

[30]  Hywel R. Thomas,et al.  Developing a curriculum statement based on clinical practice: genetics in primary care. , 2009, The British journal of general practice : the journal of the Royal College of General Practitioners.

[31]  M. Relling,et al.  Comparison of the Guidelines of the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group , 2018, Clinical pharmacology and therapeutics.

[32]  M. Relling,et al.  Development and use of active clinical decision support for preemptive pharmacogenomics , 2013, Journal of the American Medical Informatics Association : JAMIA.

[33]  Henk-Jan Guchelaar,et al.  Translating Pharmacogenomics: Challenges on the Road to the Clinic , 2007, PLoS medicine.

[34]  C. V. van El,et al.  ‘A morass of considerations’: exploring attitudes towards ethnicity-based haemoglobinopathy-carrier screening in primary care , 2013, Family practice.

[35]  G. Koppelman,et al.  What do we need to transfer pharmacogenetics findings into the clinic? , 2018, Pharmacogenomics.

[36]  M. V. Asselt,et al.  More evolution than revolution: transition management in public policy , 2001 .

[37]  Byron C. Wallace,et al.  Developing the Framework , 2013 .