Status of the implementation of pharmacogenetics in clinical practice in Spain: from regional to national initiatives

Andalusia

Andalusia had an unequal implementation of PGx across the region without any regional initiative in the Andalusian Health System. In western Andalusia, Hospital Universitario Virgen Macarena (HUVM) [10] and Hospital Universitario Virgen del Rocío (HUVR) in Seville had implemented PGx of some genes in the clinical practice (Table 1). Additionally, HUVM was involved in a multi-centric PGx pilot project, in collaboration with the Human Genotyping Unit at the Spanish National Cancer Research Centre (CEGEN-CNIO, Madrid), to evaluate the barriers in the implementation of PGx through the complete characterization of a subset of the Andalusian population [11].

On the contrary, in eastern Andalusia, there were two specific PGx units in public hospitals, one in San Cecilio Clinical University Hospital (HUCS) and another in Virgen de las Nieves University Hospital (HUVN) with different levels of implementation (Table 1). Of note, the Pharmacy Service of HUCS had been part of the H2020 project entitled “Ubiquitous Pharmacogenomics (U-PGx): Making actionable pharmacogenomic data and effective treatment optimization accessible to every patient” in which around 8,100 patients from 7 European countries were recruited and treatments adjusted based on PGx information [12].

Additionally, the Andalusian community developed an ambitious Program of Personalized Medicine [13]. This program started in 2010 with the Medical Genome Project whose aim was to address the sequencing of human genomes of phenotyped patients and control individuals [14]. This program allowed the creation of the Collaborative Spanish Variant Server (CSVS), a reference database of the genomic variation in the Spanish population [15]. Recently, PGx information have been included in CSVS to use as reference of the PGx alleles in this population. The Program of Personalized Medicine aimed at using patients’ genomic data in the clinical practice thorough the development of a bioinformatics structure to manage genomic data in a scalable, equitable and affordable manner, compatible with the General Data Protection Regulation (GDPR). Lastly, Andalusia has developed an ambitious training program in Precision Medicine (PanMEP) [16].

Basque Country

At the administrative level, there is great interest in the implementation of personalized medicine (PM). This is reflected in the creation of the Planning and Management Committee for Personalized Medicine in the Basque Country in 2021 [17], the Basque Health Research and Innovation Strategy 2022–2025 [18], the Science, Technology and Innovation Plan 2030 (PCTI 2030) of the Basque Government [19], and the Basque Oncology Plan 2018–2023 [20].

PGx testing for DPYD (5-fluorouracil, in cancer), CYP2C9 (siponimod, in multiple sclerosis), UGTA1 (irinothecan, in cancer), and CYP2D6 (eliglustat, Gaucher disease) were performed at the University Hospital Cruces and/or the University Hospital Donostia (Table 1). These tests were included in the service portfolio of Osakidetza, the Basque Health Service, and all the hospitals in the network had access to them. All petitioner physicians in the network also had access to the information about the test and the meaning of the variants. In some cancer types, tumour molecular testing was also available for treatment personalization. These techniques were implemented at the proposal of the interested services if there was a level of evidence and cost-effectiveness.

Canary Islands

The Canary medical council created in 2022 a specific commission for the development of PM. The PGx testing was included in the service portfolio of the Hospital Universitario de Canarias and the Hospital Universitario Doctor Negrín. The Institute of Technology and Renewable Energies (ITER) manages the supercomputer Teide–High Performance Computing and has a Genomics division specialized in next generation sequencing (panels, exomes and genomes) [21], 22]. ITER collaborates with the Hospital Universitario Nuestra Señora de La Candelaria (HUNSC) in research projects related to the development of PM in the Canary Islands. The project PHARMA-CAN aimed at improving drug prescription by taking into account the PGx allelic variation found in the Canarian population, using whole exome sequencing [23]. In addition, other projects focused on evaluating PGx using NGS were in progress. Besides, the Canary health service also collaborates with the IMPaCT project [8].

Castile and Leon

Castile and Leon was one of the most advanced regions in the implementation of PM in Spain at a regional level. In the clinical practice, two different protocols had been implemented: one protocol applied to diagnostics (particularly for rare diseases) with a network operation and a Regional Reference Unit on the Advanced Diagnostic of Rare Diseases (DiERCyL) [24]. And the second protocol, the 5SPM model (5 steps in PM) for the application of PGx in polymedication, carried out at the Complejo Hospitalario de Salamanca, where the specific Reference Unit for Pharmacogenetics and Precision Medicine in Castile and Leon is located [24].

In this Unit, more than 2000 cases of patients with adverse effects or therapeutic failure had been already analyzed, not only regarding their genetic factors, but also other characteristics that allow the personalisation of the therapy. This Unit has published in international journals good practice recommendations for PM and collected economic data indicate the benefit of using PM in therapy [25], 26].

In addition, this region set up the Network of Precision Oncopathology and was preparing the Strategic Plan for Personalised Precision Medicine, with the aim of implementing PGx. Castile and Leon is also involved in the IMPaCT Project, coordinating the Pharmacogenetics work package of the Genomic Medicine axis [8]. Also, the University Hospital of Burgos and the Foundation for Health Research (FBIS) participate in IPHARMGx project, a collaborative study on the implementation of PGx (see further details in the Madrid section).

Regarding research, the Instituto de Investigación Biomédica de Salamanca (IBSAL) has recently started a multicentric project on PGx in mental and cardiovascular health, funded by the call “Medicina Personalizada de Precisión” from the Health Strategic Action (AES) by the Spanish public health research institute Carlos III.

Catalonia

Catalonia had an unequal implementation of PGx across the region. Most hospitals that perform PGx studies were located in Barcelona. Some of them offered their services to external users, both for clinical and investigational purposes. The inequality was probably due to the lack of governmental initiatives for the implementation of germline PGx in Catalonia. In this sense, each hospital performed its own analyses. Whereas DPYD was genotyped in most Catalan hospitals, other interesting genes such as the ones encoding cytochromes, were determined only in a small number of hospitals. Conversely, the situation for the determination of somatic biomarkers is better established. In 2021, the ‘precision oncology program’ was implemented in Catalonia (Servei Català de la Salut) [27]. This program is an approach to the diagnosis and treatment of cancer focused on the identification of subgroups of patients with certain cancers carrying specific molecular characteristics that can be eligible to receive targeted treatments with greater effectiveness. Its main objective is to guarantee equitable access to molecular determinations and targeted treatments for all patients in the region. This program has a field of action that includes all molecular or genetic alterations that are prognostic markers or predictors of therapeutic response. The identification of these markers determines the targets that should be considered in the development of more precise drugs, and in the indication of selected treatments for certain patients. The program is divided into four different areas: haematological tumours, solid tumours, paediatric tumours, and hereditary cancer.

More recently, on the 22nd February 2023, the document entitled ‘Proposals to advance in the precision personalised medicine model in Catalonia’ was presented (Consorsi de Salut I Social de Catalunya) [28]. More than 30 healthcare professionals from institutions and centers belonging to the Catalan public health system participated in it. The aim of this work was to identify the challenges to implement a PM model in this region, and to describe the measures needed to succeed.

Extremadura

In Extremadura, the implementation of PGx was being accomplished with a centralized initiative called “MedeA–Clinical implementation of pharmacogenetics and personalized drug prescription based on e-health” [29]. MedeA is a PM strategy which integrates PGx and relevant clinical data, to develop a decision-supporting tool to be used for individualized drug prescription during regular clinical practice within the context of e-health [30].

This initiative also sought the involvement of private companies through the use of innovative public procurement as an instrument to promote research, development and innovation in companies and within the framework of the Open Innovation Model promoted by the Extremadura Health Care Service and the Spanish Ministry of Science and Innovation. MedeA was designed and developed at the Clinical Research Center of the Extremadura University Institute for Biomedical Research (INUBE), where the PGx and Personalized Medicine Unit was created and is coordinating the project. MedeA involves many services/units from all hospitals in the regional Health Care Service, as well as numerous mental health and primary care centres across Extremadura (Table 1; and for the full list of hospitals and centers participating, consult the following link: https://www.proyectomedea.es/equipo/).

MedeA program main aims are to develop: 1) a personalized prescription program incorporated into the electronic medical records (EMR), 2) an artificial intelligence algorithm for the translation of individual’s genetic information into phenotypes to facilitate drug prescription, 3) the necessary analytical and laboratory methods, and 4) methodologies to evaluate the pharmacological effects during patients’ daily lives.

At the end, the project will allow clinicians to consult automatically information regarding the PGx background of the patients within the EMR of the regional Healthcare System, allowing them to select the most appropriate drug treatment options. In addition, as the first project in this sense, it would also allow validating this approach under real clinical conditions.

Galicia

The Galician Public Foundation of Genomic Medicine (FPGMX) centralizes the genetic testing from all hospitals within the Galician Health Service (SERGAS), thus covering 3.5 million inhabitants. FPGMX is specialized in genetics of hereditary diseases, oncohematology, prenatal diagnosis, genetic counseling, PGx and research activities. PGx testing was incorporated into the Galician health care portfolio in 2004 [31], since then clinicians are allowed to request this service. A number of PGx biomarker analyses to predict drug response had been implemented (Table 1). Once a specific analysis was performed a detailed PGx report was uploaded into the EMR of the patient. Additionally, since 2021, the FPGMX was entrusted with the management of an Implementation Plan of Pharmacogenetics in Psychiatry by SERGAS, as part of the Galician Mental Health Plan post-COVID-19 [32]. This plan aimed to implement the use of PGx in psychiatry, in order to reduce hospital admissions and adverse effects of treatment, as well as increase the efficacy of the treatment [33], [34], [35]. The FPGMX not only conducts PGx analyses in relation to long-acting antipsychotics, but also extends the scope to include other drugs [34], [35], [36].

From a research point of view, the FPGMX is actively working on establishing long-lasting multidisciplinary collaborations with medical and pharmaceutical teams to promote and coordinate translational projects in PGx. These activities are developed in collaboration with different entities, such as the Santiago de Compostela Health Research Institute (IDIS), the Genomic Medicine Group, the Universidad de Santiago de Compostela (USC) and the Biomedical Research Network on Rare Diseases (CIBER).

At present, the FPGMX leads projects in different areas being some of the most recent: PM for the administration of methadone based on PGx profiles, optimization of schizophrenia treatment using OMIC data and systems biology (SchizOMICS), and omnigenic view of genetic susceptibility to severe COVID19 [31].

FPGMX is a member center of the Genomic Analysis Network within the Genomic Medicine Axis of the IMPaCT Platform [8]. Also, it is important to highlight that the FPGMX obtained funding and takes part in the Precision Medicine Research Projects (ISCIII) such as “Evaluation of a Proposal for the Implementation of Pharmacogenetics in the National Health System for Mental and Cardiovascular Health (BioFRAM)” and participates at “Clinical and PGx interventions in childhood and juvenile population (INGENIA)”.

La Rioja

In order to advance in the implementation of PM, in 2016, La Rioja healthcare service created a Committee on Genetic Counselling to unify the petition and approval of genetic tests requested by the clinicians. The Clinical Analysis Laboratory at Hospital Universitario San Pedro performed PGx testing for DPYD (for fluoropyrimidine drugs), UGT1A1 (irinotecan), CYP3A5 (tacrolimus), CYP2C9 (siponimod) and SLCO1B1 (statins) [37]. Physicians in the public network were able to request these tests and also tumor molecular testing for treatment tailoring in certain tumor types. Moreover, the Hospital announced the creation of a Precision and Personalized Medicine Unit [38]. This Autonomous Community uses the EMR for each patient which also includes the genetic information that can be securely accessed by the specialist.

Regarding Research and Innovation Projects, the region launched the “Smart Specialization Strategy (RIS3, 2014–2020), the “V Plan Riojano de I+D+I” (2017–2020) and the “I Strategic Plan of Innovation in Health” (2017–2022) [39], 40]. Within these plans, PM is recognized as one of the future areas and is established as a funding priority. However, the specific objectives and measures to implement it need to be further developed. La Rioja also has a Biomedical Research Center (CIBIR) with research lines focusing on rare diseases, oncology, infectious diseases and neurodegeneration using next generation technologies and Big Data [41]. The CIBIR also counts with several Genomics & Bioinformatics and Biomedical Research platforms.

Madrid

In the region of Madrid, there is a regional initiative for the implementation of PGx under development. The main PGx units in public hospitals in this region are located in University Hospital (U.H.) La Princesa, U.H. Gregorio Marañón and U.H. La Paz (Table 1) [42], [43], [44]. These units also offer their services to external users, both for clinical and investigational purposes. In addition, some of these PGx units have demonstrated the utility of the implementation of pre-emptive PGx through research studies. Noteworthy, U.H. La Paz presented their experience after 3 years of pre-emptive PGx testing [45] and U.H. La Princesa is developing a multidisciplinary initiative named “PriME-PGX” to implement PGx in their hospital [46], and also contributing to the expansion of PGx knowledge among professionals, the general population and throughout the field of clinical trials. Other hospitals in the region that offered PGx tests in their service portfolios include U.H. Ramón y Cajal, U.H. Clínico San Carlos, U.H. Severo Ochoa and U.H. Fuenlabrada. The detailed level of PGx implementation of each hospital is showed in Table 1. In all cases, PGx reports include both genetic determination result and treatment recommendations (indication and or dose adjustments) for relevant gene-drug pairs. Moreover, research projects on PGx are developed at different hospitals and research centers such as IPHARMGx [47]. This is a National collaborative study, coordinated by the Clinical Pharmacology Department at U.H. La Paz, to evaluate the efficacy and cost-effectiveness of the implementation of PGx biomarkers through an anticipated genotyping strategy in the NHS. It involves more than 60 researchers from 11 hospitals (also in Madrid: U.H. Gregorio Marañón, Health Research Institute Gregorio Marañón and the Nephrology department at U.H. La Paz). Some of the axes of this study include PGx in kidney transplant patients and in high cardiovascular risk patient, among others. Additionally, Human Genotyping-CEGEN Unit at the Spanish National Cancer Research Centre (CNIO) offers a comprehensive PGx analysis, which includes 17 genes and 59 drugs to public hospitals of this region or other Spanish regions, facilitating their access to PGx analysis [48]. In this sense, a multicentric PGx pilot project in collaboration with different hospitals from Madrid, Balearic Islands and Andalusia is ongoing to evaluate the barriers of PGx implementation across the country in more than 300 Spanish patients. In addition, a recent study accomplished by CEGEN-CNIO in collaboration with the Clinical Bioinformatics Unit from HUVR has performed a comprehensive analysis of the genetic variability of 21 pharmacogenes in more than 3,000 Spanish individuals, evaluated the clinical impact on 64 drugs as well as determined PGx CNVs [49], 50]. Genetic data is available through the CSVS portal (http://csvs.babelomics.org/) [15].

Navarra

Until recently, the use and implementation of PGx in Navarre was mainly focused on the determination of tumor alterations (e.g. ALK translocations, BRAF and EGFR mutations, BCR-ABL fusion) and HLA-B typing. These tests were performed by the Anatomical Pathology, the Medical Genetics and the Immunology Departments of the University Hospital of Navarra (HUN) from the public healthcare system–Osasunbidea. Testing of CYP2C9 and DPYD have also been incorporated into the clinical practice (Table 1).

The Navarre regional government has promoted strategic projects on Personalized Medicine (RETO GEMA) [51] and since 2016, the HUN and Navarrabiomed have pursued the implementation of genome sequencing as a clinical tool to develop personalized medicine in the public healthcare system (Nagen program [52]). Specifically to this review, the Pharmacy Service of the HUN and the Genomics Medicine Unit of Navarrabiomed developed PharmaNAGEN project [53]. This study evaluated the use of NGS as a clinical tool to obtain PGx data to improve treatment decisions in more than 250 individuals. The initiative aimed to develop a pharmacogenetic alert system implemented into the electronic clinical decision support system of the public healthcare. The prescription assistance tool, based on the individual PGx profile, will offer recommendations to clinicians to individualize the therapies. This will include recommendations for 52 drugs affected by the genotype of 13 genes. PharmaNAGEN paved the way for the implementation of PGx data in the healthcare system, acquiring the knowledge, developing the tools and training of clinical experts so that patients can benefit from personalized drug prescription [54], 55]. In addition, clinicians and researchers from the Biomedical Center of Navarre (Navarrabiomed), Navarra Services and Technologies (NASERTIC) and HUN are also participating in IMPaCT projects [8].

Valencian Community

In the province of Valencia, the University General Hospital of Valencia, Sagunto Hospital, La Fe Hospital and Arnau de Vilanova Hospital performed PGx testing. Each hospital performed its own analyses, ranging from a few genes to more than 10 genes, and provide with PGx reports. Moreover, various projects are currently being carried out for the implementation of PGx in clinical practice. IMPaCT project includes PGx within the IMPaCT-GENÓMICA program and its objective is to lay the foundations for the implementation of PGx tests in the NHS [8]. La Fe Hospital/Health Research Institute (IIS) in Valencia participate in this project in collaboration with other national centers [8]. Aligned with IMPaCT, the BioFRAM project aims at individualizing the prescription of drugs used in mental and cardiovascular diseases based on PGx markers for the prevention of adverse reactions. In this region, Hospital La Fe, Hospital Clínico, Hospital Doctor Peset and primary care centers are involved in this collaborative study.

In addition, the Pediatric Oncology Unit of Hospital la Fe together with the PGx Unit of IIS La Fe is carrying out, as part of the neuroblastoma European project ‘HR-NBL2/SIOPEN’, an independent work on the PGx of high-risk neuroblastoma patients to establish associations with drug side effects [56]. The abovementioned PGx Platform at IIS La Fe also investigates the association of PGx with immunosuppressants in organ transplantation, as well as it offers services to design PGx panels and validate PGx markers [57].

The PGx Platform of the Alicante Health and Biomedical Institute (ISABIAL) is currently participating in the project called IPHARMGx [47]. ISABIAL is also conducting a clinical trial (EudraCT Number: 2021-001238-21) entitled “Gender biases in pain medicine: from omics to healthcare” that integrates PGx, epigenetic, and metabolomic markers to understand the gender differences observed in the analgesic response to opioids.

Also, at Miguel Hernández University, a research project is being developed focused on the genetic variation and functional analysis of cytidine deaminase enzyme (CDA) activity to categorize it as a biomarker of oncological treatment toxicity [58].

Other Spanish regions

Some Spanish regions did not present a PGx clinical implementation structure although the main hospitals of these regions performed PGx testing for some genes (e.g. DPYD, TPMT or UGT1A1).

This was the case of Aragon, although they showed interest in PGx and PM since 2010 [59], the implementation of PGx began at the end of 2020 with the DPYD alert from the Spanish Agency of Medicines and Medical Devices (AEMPS). Since then, genotyping of the population of the entire region was centralized at the Miguel Servet Hospital, located in Zaragoza, specifically at the Genetics Unit. The Pharmacy Department prepares the reports for each genotyped patient (Table 1).

In Asturias, the Genetics and the Molecular Oncology Units at the Central University Hospital of Asturias (HUCA) screen for CYP2C9, CYP3A4 and UGT1A as per the hospital portfolio [60]. Also, the University of Oviedo and the Healthcare Research Institute of Asturias are participating in the IMPaCT project [8].

In Balearic Islands, the Son Espases Hospital set up the Genetic and Genomic Unit, which aims at acting as the diagnostic reference for genomic analysis in the regional healthcare service. Furthermore, the Clinical Analysis Unit of the Hospital includeed PGx testing in the portfolio, although it was not yet included in other hospitals. The region also collaborates with the IMPaCT project through the Health Research Institute of the Balearic Islands (IdISBa) [8].

In Castile-La Mancha, the main hospitals of Toledo, Ciudad Real, Cuenca and Albacete had implemented the PGx testing through their Clinical Analysis Units. They mainly performed the analysis of DPYD but also CYP2C9 and HLA-B in some cases (Table 1). Also, researchers and clinicians from the Tomelloso Hospital and the Health Research Institute of Castile-La Mancha participate in the iPHARMGx project (already mentioned in the Alicante region) [47].

In Cantabria region, at the Marqués de Valdecilla University Hospital, TPMT polymorphism determinations were carried out in patients treated with azathioprine and MTHFR polymorphism determinations for hematological diseases. Negotiations were underway between the Molecular Genetics Service and Clinical Pharmacology of the same hospital to carry out laboratory tests by the Molecular Genetics Service, while the Clinical Pharmacology Service would prepare clinical reports for patients. Also, researchers and clinicians from the Marqués de Valdecilla University Hospital and Valdecilla Research Institute (IDIVAL) participate in the iPHARMGx project [47].

In Murcia, the Molecular Diagnostic Laboratory of the University Hospital Complex of Cartagena analyses DPYD, UGT1A1, IL28, CYP2C9, CYP2C19 genes and the Genomics Laboratory of the Hematology Service of the University General Hospital Morales Meseguer studies UGT1A1 and DPYD (Table 1) [61]. Both hospitals screen for somatic alterations with predictive value in neoplasias (e.g., BCR-ABL, BRAF, EGFR, TP53). Hospitals from this region also collaborate with the IMPaCT project [8].

IMPaCT project

IMPaCT is the Precision Medicine Infrastructure associated with Science and Technology [8]. This infrastructure is designed to provide service to the research, development and innovation system oriented to PM, to promote the generation and transfer of high-quality knowledge in the NHS, ensuring scientific-technical excellence, equity and efficiency in the use of the available resources. The IMPaCT Strategic Plan is configured around three strategic axes (Predictive Medicine, Data science and Genomic Medicine) and two transversal strategic lines. The strategic axes are arranged in specific actions and work packages, with compliance indicators that should allow verifying the effectiveness of infrastructure deployment (Figure 1).

Figure 1:

Strategic axis of IMPACT project.

In a complementary way, the two transversal strategic lines are common to the above mentioned three axes and they provide internal coherence. The first transversal line refers to Ethics and scientific integrity, and the second one to Internationalization. This later aiming to position Spain as an international benchmark in the field of PM.

Specifically to the topic of this review, in the Genomic Medicine axis, one of the areas of application was PGx [62]. The main objectives of this part were to lay the foundation to allow PGx testing implementation in the NHS, and also to provide with genomic diagnostic services equitably across the country to individuals with serious drug or vaccine adverse events. This working group put all their efforts to: 1) connect with the Pharmacovigilance network and establish the samples workflow, 2) create Expert and Result Interpretation Committees, 3) establish and renew standardized laboratory protocols for drug adverse events, 4) elaborate Clinical Guidelines and a clinical report template, 5) provide diagnostic genomic services in a fair manner across Spain, 6) federated data sharing and data discovery, and 7) interrelate with the Predictive Medicine axis.

SEFF implementation strategy

There are many successful cases in which PGx was implemented in the clinical practice, where, based on the clinical guidelines established by the Clinical Pharmacogenetics Implementation Consortium (CPIC), genotyping began to be carried out prior to the prescription of certain drugs such as warfarin, clopidogrel, codeine, antidepressants and antiepileptics [3], [63], [64], [65], [66], [67].

Similarly to other national/international PGx groups, the Spanish Society of Pharmacogenetics and Pharmacogenomics (SEFF) is a national multidisciplinary scientific society actively working on the development of PGx guidelines in Spanish. The SEFF developed the General Strategy for the Clinical Implementation of Pharmacogenetics with the overall objective of generating recommendations for the implementation of the PGx to optimise the safety and efficacy of the pharmacological treatments taken by patients [68]. More than 50 experts in the field are working together organized in working groups (WG1. PGx regulation–List of recommended drugs; WG2. Methodology and analytical interpretation; WG3. Clinical recommendations; WG4. Solid tumors) and programmes (1. Proficiency testing, 2. Teaching-training, and 3. Map of the labs and PGx services in Spain).

The advancement in PGx must be in line with therapeutic guidelines and regulatory agencies; however, progress in this area is often slow. As a consequence of this situation, the SEFF is working on the development of clinical recommendations based on the existing evidence, so that these can serve as a basis on which to start implementing PGx in the clinic [69]. So far, it has generated clinical recommendation documents for 12 gene – drug pairs that are available at the SEFF website (https://seff.es/), as well as published a consensus paper in collaboration with the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines [70]. More documents are in progress. With this strategy, SEFF wants to become a fundamental element in the Spanish Strategy for Personalised Medicine promoted by the National Government and to facilitate the implementation of the current NHS PGx portfolio.

National PGx implementation strategy

At the national level, a Working Group of experts reporting to the Healthcare Ministry has been working on updating and specifying a common portfolio of services in the area of genetics for the NHS in order to guarantee a more homogeneous and equitable access to all individuals who require these tests within the NHS.

The first version of the catalogue, that will need continuous updating, was approved in the plenary session of the Interterritorial Council of the NHS on June 23rd 2023, and presented it on January 23rd 2024 by the Healthcare Ministry [71]. The proposed catalogue was developed by eight subgroups, with the participation of representatives from the Autonomous Communities, Spanish scientific societies, the health research institute Carlos III (ISCIII) and the Network of Agencies for Assessing NHS Technologies and Performance, for these prioritized areas: adult onco-hematology, pediatric onco-hematology, pharmacogenomics, heart disease and disorders of the circulatory system, ophthalmological diseases, hereditary metabolic and mitochondrial diseases, neurological diseases and neuromuscular/neurodevelopmental disorders including cognitive deficits.

It is worth mentioning that this is the first PGx catalogue approved at a national healthcare level in Europe. It includes 12 genes, for 22 main drugs and the clinical indication criteria for each test (Table 2 and in the link: https://cgen.sanidad.gob.es/#/consulta-general). Information on the type of technique and the indispensable variants is also included, and it is warned that the obtained genetic information can be used for the adjustment of other treatments that also have specific recommendations. In addition, the Spanish Agency for Medicines and Medical Devices (AEMPS, abbreviation in Spanish) has recently published a database with PGx biomarkers to facilitate the implementation of PGx in the clinics (https://www.aemps.gob.es/medicamentos-de-uso-humano/base-de-datos-de-biomarcadores-farmacogenomicos/). This resource provides with the regulatory information included in drug data sheets, and in the near future, it will also contain the established recommendations for each active compound.

Once the appropriate regulatory development is in place, each Autonomous Community will need to establish the necessary circuits to ensure adequate patient access. To this end, some regional groups have already started working, and important developments will come throughout this year.