Pharmacogenomic Testing: Clinical Evidence and Implementation Challenges

Abstract

Pharmacogenomics can enhance patient care by enabling treatments tailored to genetic make-up and lowering risk of serious adverse events. As of June 2019, there are 132 pharmacogenomic dosing guidelines for 99 drugs and pharmacogenomic information is included in 309 medication labels. Recently, the technology for identifying individual-specific genetic variants (genotyping) has become more accessible. Next generation sequencing (NGS) is a cost-effective option for genotyping patients at many pharmacogenomic loci simultaneously, and guidelines for implementation of these data are available from organizations such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). NGS and related technologies are increasing knowledge in the research sphere, yet rates of genomic literacy remain low, resulting in a widening gap in knowledge translation to the patient. Multidisciplinary teams—including physicians, nurses, genetic counsellors, and pharmacists—will need to combine their expertise to deliver optimal pharmacogenomically-informed care.

Clinical implementation of preemptive pharmacogenomics in psychiatry: Τhe “PREPARE” study

“…For now, the implementation of PGx in everyday clinical routine faces various obstacles, such as awareness of the population and clinicians, bioinformatics issues, and very importantly, costs. 15 On the other hand, PGx carries the promise of benefits for the patients, in terms of efficacy and safety, whereas cost-effectiveness remains to be demonstrated. The present study aims to better define these obstacles, to find ways of remediation, and determine cost parameters.…”

“…Such obstacles include, among others, lack of clinicians' confidence and familiarity with genetics and genomics, logistics and infrastructure of incorporating PGx testing into the clinical routine, public attitudes, cost and ethical issues. 15 Secondly, it aims to provide evidence that PGx testing can aid the choice of the right drug at the right dose based on the patients genetic background. 16,17 For this reason, training of the physicians and the health professionals participating in the program has been undertaken, as well as the registering of the pharmacogenes and the guidelines per drug, according to the Dutch Pharmacogenomics Working Group Guidelines-DPWG, www.dpwg.org, the installation of the equipment required for the analyses and the development of the appropriate bioinformatic tools for the translation of the genotype results into actionable and usable information for the clinician.…”

Rural Community Perceptions and Interests in Pharmacogenomics

“…To move the field of pharmacogenomics forward to treat patients with diseases such as mental disorders, pain, inflammatory disease, cardiovascular disease, or cancer, it is going to require a concerted effort of education. The current barriers to pharmacogenomics are insignificant to the relentless mountain of evidence that continues to grow for the use of pharmacogenomics [ 32 ]. As we continue to learn how to use it, it will continue to become more accessible, and costs will continue to drop, thus the barriers will not prevent the research community from assessing the true impact of pharmacogenomics testing.…”

<p>Physicians’ Attitudes and Ethical Obligations to Pharmacogenetic Testing</p>

“…34 As incidental findings pose additional concerns for health-care providers and patients, reporting incidental findings for genetic variants of identified clinical significance during subsequent analysis of the resulting genetic data, could help mitigate these concerns and identify which incidental findings should be further assessed. 35 The American College of Medical Genetics and Genomics (ACMG) developed recommendations for reporting secondary findings whenever considered clinically meaningful or actionable, for example, the association of malignant hyperthermia with pathologic variants of RYR1 gene. 36 As a general agreement, medically actionable incidental findings should be offered to patients or routinely reported to them; however, more studies are needed to support physicians' ethical decision-making and promote evidence-based practices regarding the extent of disclosing different incidental information.…”