Clinical Implementation of Pharmacogenetic Testing in a Hospital of the Spanish National Health System: Strategy and Experience Over 3 Years

Abstract

In 2014, we established a pharmacogenetics unit with the intention of facilitating the integration of pharmacogenetic testing into clinical practice. This unit was centered around two main ideas: i) individualization of clinical recommendations, and ii) preemptive genotyping in risk populations. Our unit is based on the design and validation of a single nucleotide polymorphism (SNP) microarray, which has allowed testing of 180 SNPs associated with drug response (PharmArray), and clinical consultation regarding the results. Herein, we report our experience in integrating pharmacogenetic testing into our hospital and we present the results of the 2,539 pharmacogenetic consultation requests received over the past 3 years in our unit. The results demonstrate the feasibility of implementing pharmacogenetic testing in clinical practice within a national health system.

Keywords: individualization; pharmacogenetics; precision medicine.

Figure 1

Classification of pharmacogenetics tests and pharmacogenetics unit workflow. We have divided pharmacogenetics tests into three main groups: For drugs belonging to group (a) in which the pharmacogenetics test is required before treatment prescription, requests and samples are directly forwarded to the genetics department (INGEMM) for sample processing and analysis. The final molecular report is directly sent to the petitionary service for treatment selection. Groups (b) and (c) share a different workflow: Petitionary services refer their request, including all clinical information, to the pharmacogenetics unit that will decide whether a pharmacogenetics test is indicated in each case. If the pharmacogenetics test is recommended, molecular analysis is performed in INGEMM and a genetic report is generated. Taking into account the molecular result and the clinical information of the patient, a final clinical recommendation is given to the original petitionary service. Clinical recommendations are specific for each patient because they are generated relying on a multifactorial basis. It is important to notice that groups (b) and (c) might share some particular drugs (e.g., voriconazole), given these might have a protocol when prescribed for a particular disease but not for a different pathology.

Figure 2

Analysis workflow. Our custom analysis workflow includes six main steps performed by both the Clinical Pharmacology Department and the INGEMM pharmacogenetics specialists. First, genomic DNA from the patients is automatically extracted from peripheral blood cells using Chemagen technology (Perkin‐Elmer, Boston, MA). However, in particular patients, DNA can be obtained from other biological samples such as saliva or tissue. It is necessary that all patients give informed consent to genetic analysis. Subsequently, a TaqMan OpenArray Genotyping Assay is performed using our custom design (PharmArray; Reg. no. 4571001). An individualized analysis of each SNP included in the pharmacogenetics protocol for each specific drug and disease is then performed. We then proceed to haplotype and diplotype inference using population databases and codification using the star‐allele nomenclature (^*). Once genotypes are codified, phenotypes are also inferred. Finally, an integration of both the clinical and molecular information is performed for a more individualized clinical recommendation.

Figure 3

Patient Enrollment (2014–2016). Distribution of the 2,539 pharmacogenetics tests performed in our Pharmacogenetics Unit. PhGx: Pharmacogentic.