Drug therapy cannot be viewed as one-size-fits-all
More than 90% of individuals carry at least one potentially actionable pharmacogenetic variation[1], giving pharmacogenomics (PGx) growing importance in clinical decision support. Additionally, non-European populations carry a greater frequency of variants, many not yet captured by current PGx allele definitions, that are predicted to be harmful[2].
Without knowledge of pharmacogenetic factors, improper drug selection and administration can result in reduced therapeutic response or serious adverse drug reactions (ADRs), the latter of which is estimated to be the sixth leading cause of death worldwide.
Some examples of clinically significant genomic variants influencing mediation therapy include:
- Reduced cytochrome P450-mediated opioid metabolism, which could lead to excessive respiratory depression and death
- Effects of decreased TPMT metabolism on thiopurine treatment, which could predispose to serious blood toxicities
- Effects of reduced liver uptake of sim-vastatin, which could lead to significant muscle damage. However, preemptive pharmacogenomics testing is still emerging as best practice, translating genotypes into actionable phenotypes.
While PGx is a subject that intrigues many clinicians, transitioning it into a practical component of the diagnostic and treatment routine will require access to consistent, evidence-based PGx data and a team-based approach involving healthcare professionals from prescribers, pharmacists, and nurses, to lab technicians and those managing benefits.
Awareness: Engaging clinicians on how, when, and why to use PGx
Clinicians are aware of the impact of genetic factors on drug therapy, but don’t always feel prepared to implement that in- formation into their daily practice:
- A survey of 285 physicians from five of the Implementing GeNomics In pracTiCe (IGNITE) clinical trial network sites revealed that most physicians felt unprepared to use genetic information in their practice and believed steps needed to be taken to develop tools and training for physicians. Those with five years or fewer in practice were more likely to report that their training had prepared them to care for genetically high-risk patients compared with those with over five years’ experience (41% vs 25%)[3].
Recognizing the need to help clinicians understand the importance of pharmacogenomics early on, Wolters Kluwer has curated clinically relevant PGx content since 2003 and is widely recognized as a leader in providing extensive and actionable clinical guidance on important PGx interactions.
This content covers the prevalence of genomic variants in patient populations, the utility and interpretation of laboratory testing, and subsequent clinical recommendations[4]. For clinicians working at the point of care, drug-gene summary monographs provide testing and patient management recommendations from authoritative clinically actionable guidelines[5].
When more comprehensive research data is required, clinicians need access to in-depth pharmacogenomics content.
To accommodate this need, Lexicomp® core drug monographs contain links to detailed, extensively referenced gene-based monographs which provide an overview of the population incidence of the most common or clinically important gene variations and the relevance to drug response. Online and mobile pharmacogenomics drug references also offer benefits outside of the direct care arena, providing valuable genetic research information for medical affairs departments and R&D and important safety context for healthcare benefits businesses, which have been slowly expanding coverage for gene testing over the past decade.
Alerting: Getting the right data into clinicians’ hands
Interviews with general practitioners in the United Kingdom revealed that most saw value in PGx but felt there were many obstacles to primary care embracing it in everyday practice, including educating clinicians, cost effectiveness, and incorporating the information into electronic health records[6].
Currently, integrating genomic data and clinical decision support tools into electronic health records is one of the largest barriers to more widespread adoption of preemptive pharmacogenomics testing. The Electronic Medical Records and Genomics (eMERGE) Network is leading the way in piloting and implementing PGx and integrating the results within EMR and clinical decision support systems in the U.S.
A survey of 10 of the sites within the network reported that delays in the process were not stemming from the pharmacogenomics testing itself, but more likely to be related to health information technology, among other logistical issues[7].
Pharmacogenomic data embedded within an EMR, clinical, or pharmacy system serves as a powerful tool for getting vital data before the clinicians’ eyes at the right time in the decision-making process. A smartly designed system with evidence-based data can help prevent high-risk patients from being exposed to “dangerous” drugs due to their genetic predispositions. Such a system would provide appropriate dosage recommendations based on relevant genetic variance and would only alert on known risky combinations, optimizing the alerts that fire in the system.
Wolters Kluwer looks to help clinicians overcome some of those technological barriers by infusing Medi-Span® embedded drug data modules with evidence-based and actionable pharmacogenomic data that aligns with respected Lexicomp content and by providing clear guidance and best practices on how to optimize and apply relevant pharmacogenomics data.
Alignment: PGx works best when care teams work together
With resources available at the point of care and in the EMR, the final element to successful adoption of PGx is human. Many clinical and non-clinical personnel need to collaborate, communicate, and align resources to fully integrate PGx into an organization’s regular practice.
As well as systems or infrastructure to support these needs:
- IT/EMR set-up and maintenance of ap- propriate PGx screening and alerts
- Process for documentation of relevant medication and family histories
- Billable-service provider
- Mechanism for reporting results
Wolters Kluwer’s investment in pharmacogenomics content seeks to benefit all members of this multi-disciplinary care team by providing solutions that centralize and standardize delivery of this content to the right provider, at the right time, providing insight and context relevant to the right patient.
Conclusion
As more clinicians adopt, adapt, and learn about personalized medicine and pharmacogenomics, it will only increase medication safety in the future. Peter Bonis, MD, Chief Medical Officer for Wolters Kluwer Clinical Effectiveness, notes that “scientific advances continue to offer new options for medications that have the potential to improve and save lives. The affordability of these drugs has spawned vigorous public debate. Equally important – but less in the public dialogue – are efforts to ensure that drugs are used both wisely and safely. Pharmacogenomics represents one such approach toward precision prescribing.”
References
- Van Driest et al, Clin Pharmacol Ther. 2014 Apr; 95(4): 423–431.
- https://pubmed.ncbi.nlm.nih.gov/33237584/
- https://pubmed.ncbi.nlm.nih.gov/30042363/
- Chang et al, J Med Libr Assoc. 2016 Jan;104(1):58-61; Vaughan et al, J Med Libr Assoc. 2014 Jan;102(1):47-51.
- Clinical Pharmacogenomics Implementation Consortium (CPIC): https://cpicpgx.org/guidelines/; Dutch Pharmacogenetics Working Group (DPWG): https://www.knmp.nl/patientenzorg/medicatiebewaking/farmacogenetica/pharmacogenetics-1/pharmacogenetics; FDA Table of Pharmacogenomic Biomarkers in
Drug Labeling: https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling. - J Community Genet. 2020 Jul;11(3):269-doi: 10.1007/s12687-020-00468-2. Epub 2020 May 28.
- https://www.sciencedirect.com/science/article/pii/S1098301516313079
