Teaching Pharmacogenetics / Pharmacogenomics and Genetics in the Faculties of Pharmacy of Spain, the causes of delay.
Andrés Corno Caparrós. -a, Pedro García Salomb and Amparo Soria Aledoc a Genetic Analysis ANCOR, Alicante, Spain.-b Hospital Vega Baja-Alicante, associate professor UMH, Pharmacy and pharmaceutical technology, Alicante, Spain -c Orihuela-Alicante Health Department, Associate Professor UMH, Business Organization Received October 10, 2016; accepted March 29, 2017. Available online June 2, 2017.
Summary: The subject of Pharmacogenetics / Pharmacogenomics (FG) is taught in 26.1% of the Faculties of Pharmacy (FF), being its percentage in the private schools of 40% and in the public 15.3%, and Genetics 30.4%, homogeneous in both. 6 years ago, ˜ in 2010, and referred At the FG, this percentage was more than 3 times higher (89.3%) in the United States FF. The The highest percentage of those in which none of the 2 subjects is taught occurs in the faculties that concentrate the largest offer of places.
In those that impart them, the character it is mostly mandatory. 6 ECTS credits are devoted to the Genetics subject and to the FG 3 ECTS. Both have a marked theoretical character, with little or no training inthe experimental, analytical, clinical or health field. The formative inequalities of these subjects in our country, when knowledge is universal, lay the foundations for aunequal application of scientific advances and condition the principle of universality of our healing. This lack of knowledge today prevents a safe and efficient dispensing ina good number of drugs following the recommendations of regulatory agencies, such as the European Medicines Agency or the Food and Drug Administration.
Introduction. Pharmacogenetics is a basic and applied science that has its origins in works of confluence in Genetics, Biochemistry and Pharmacology. And in the publication, recognized as Arno Motulsky's seminal on pharmacogenetics «As an experimental science relating to interpersonal differences in response to drugs that manifest themselves as a consequence of the unique genetic makeup of the people »1. Vogel in 19592 coined the term pharmacogenetics and proposed that it be applied to the study of the effects of inheritance in pharmacological response. Werner kalow In 1962 he published the first systematic work on this science. Despite its beginnings in the 1960s, it has been from the Human Genome Project (1990-2003), technological development and investment in research, specifically in pharmacogenomics (GFR) since the year 2000, which has led to an extraordinary development of the itself, making tangible to clinicians and society the personalized medicine3,4.
The GF constitutes a central axis of the pharmaceutical sciences, just as anatomy is it of the medical sciences. It is the science that is allowing to know and characterize in detail the internal environment that accounts for the answer therapeutic in any person to whom a drug is administered. Of all those genes and proteins that mediate pharmacokinetics and pharmacodynamics; specifically 38 gene families and 925 genes (table 1) that must be known by all those for whom the drug constitutes an axis of his professional activity. It is a science that allows answering questions such as: How many drug targets are covered by authorized drugs? Or how many potential targets are there? 5. It has been become an indispensable science in research,development and dispensation, as it was in the decade of the 80 genetic engineering in the manufacture of drugs, becoming a useful tool for a prescription safe and effective. It is allowing us to know in detail the molecular mechanisms that account for the appearance and progression of diseases, laying the foundations for more precise prevention and treatment strategies. As Collins said in the presentation of the “Precision Medicine” 3 strategy, give the right drug to the right person at the right time and at the right dose based on their genetic characteristics. New knowledge that involves significant changes when it comes to approaching the best approach for the patient; from evidence-based drug therapy (often not applicable to a specific patient) to mechanism-based drug therapy, giventhat the pharmacogenetics of the patient plays a role determinant in the answer 6.
Pharmacists (F) as providers at the point of care and drug experts are exceptionally positioned in the health system to educate other health professionals once they are updated in these matters and to patients on the interpretation and application of results of pharmacogenetic tests. The formation of the F and their practical background also allow them to participate in thedevelopment of the FG and promote its integration. Via these activities, the F has the possibility and potential to be a fundamental part in this new era of medicine custom 7.
Therefore, it is necessary that universities, and in The government teams of the faculties that teach degrees in Health (Pharmacy, Medicine, Nursing and others) of our country, as well as the rest of the countries of the European Union were the champions of this evolution with clinical implications on the health of the population.
Table 1 The pharmacogenomic space. Pharmacogenes of metabolization and target pharmacogenes, their number, number of families and examples of some with clinical utility.
Stages of metabolization No. of genes families Eg genes with variations. Clinical utility Fase I. Activation 110-7 CYP2D6,CYP2C19,
CYP3A5 Fase II. Conjugation 99-6 UGT1A1,TPMT Fase III. Transport 454-2 (SLC-ABC)
SLC01B1 Fase IV. R. nucleares 48-7 VDR
Material and methods In this study we have started to identify the Spanish universities ˜ that offer the academic degree of Pharmacy, from the list of offer of degrees of the Ministry of Education, Culture and Sports of 6 July 2015. According to the same, the degree of Pharmacy in 23 universities, with 13 being public schools and 10 private ones. Being the public the faculties of Pharmacy (FF) of: Murcia, Complutense de Madrid, La Laguna, Valencia General Studies, Alcalá de Henares, Miguel Hernández-Elche, Basque Country, Salamanca, Castilla-La Mancha, Barcelona, Santiago de Compostela, Granada and Seville. And the private ones those of: Alfonso X el Sabio, Cardenal Herrera CEU, Catholic of San Antonio, Navarra, Francisco Victoria, Europea from Madrid, San Pablo CEU from Madrid and the Ramón Llull de Blanquerna, and the Technical School Superior IQS.
From the web pages of each university, the study plan was analyzed first and the second place, and whenever possible, to the analysis of the guidelines teachers and subject files to know the content of the same in a way that allows an analysis precise of the situation in Spain. After the analysis of the programs and the guidelines, the data obtained in the form of a table (table 2), reviewing the university, the number of places offered, its nature ublic or private, the presence in the curriculum of the subjects: Genetics, Pharmacogenomics or Pharmacogenetics or one with a close name, its optional nature or compulsory, the number of credi s and, finally, the presence of practices of an experimental, analytical or clinical reference to the aforementioned subjects.
Goals. The objective of this study is to have an X-ray of higher education, specifically of studies degree of FF referring to GF, Pharmacogenetics and Genetics. Analyzing both their presence in the plans studies and its optional or compulsory nature, such as its extension and contents. The analysis of the results should constitute a basis for reflection and the approach of strategies that allow correcting possible inefficiencies.
Results. Presence of materials The results obtained are reflected in Table 2. In Regarding the presence of the Genetics subject, it is verified that it is present in 7 of the universities, which represents 30.4%, being compulsory subject in 6 of them and optional at the Francisco de Victoria University. Breaking down by public or private nature, Genetics is taught in 4 of the 13 public universities, they represent 30.7%, and in 3 of the 10 private ones, that is to say in 30%. Regarding the subject of Pharmacogenomics or Pharmacogentics, this is taught in 6 of the 23 universities, which represents 26.1%. In the breakdown by the public or private, it is taught in 2 of the 13 public, represents 15.3% and in 4 of the 10 private, which represents 40%. Regarding the presence of practices, whether experimental, analytical or clinical, just appears reflected as such in 1 university, which is that of Castilla la Mancha. The existence of this type of training in the total of the 23 universities it is therefore 0.04%. In the breakdown by public and private, presence in public one, which represents 0.08%, and in private 0, which represents 0%.
Number of credits. Regarding the number of credits: in the subject of Genetics the number of ECTS is 6 in 6 of them and 3 ECTS in the Francisco de Victoria. In the subject of Pharmacogenetics and Pharmacogenomics it is 3 ECTS in 4 faculties, 4 ECTS at the Salamanca FF and 6 ECTS at the Castilla-La FF Stain. Mandatory or optional nature of the subjects.
Regarding the compulsory or optional nature: the subject of Genetics is compulsory in most of them, in 5 of 6, and optional character in one. The subject of Pharmacogenetics and Pharmacogenomics has the character Mandatory at 5 out of 6 universities. We can summarize by saying that the subject of Genetics is taught in 30.4% of Spanish FF, which has a fundamentally compulsory nature with 6 ECTS. On Regarding Pharmacogenetics-Pharmacogenomics, it is taught as such in 26.1%, with a greater presence in the private ones (40%), having a character mainly compulsory, with an extension of 3 ECTS in the highest number of them.
Contents of the subject Pharmacogenomics / Pharmacogenetics. Of the 6 faculties that teach the subject of Pharmacogenetics-Pharmacogenomics as such (in the case of the 2 of Blanquerna the title of the subject is: Individualized Therapy-Pharmacogenomics), it has only been possible access the contents of 3 of them, those corresponding to the faculties of Salamanca (19 subjects 4 ECTS OB), Castilla-La Mancha (6 subjects-6ECTS OB) and Francisco de Vitoria University (12 subjects-3 ECTS OP). We can say that in the contents are balanced, with basic aspects and applied to pharmacological groups of diseases. On the section on experimental, analytical or clinical teaching, only in the faculty of Castilla-La Mancha is the existence of 20 hours of laboratory practices.
Contents of the Genetic matter. In general, in the 6 FF that teach the subject with such name or with other names, such as Molecular Genetics (Francisco Victoria), Genetics Applied to Pharmacy (Miguel Hernández University) or Immunology, Genomics and Pharmacogenomics (Alcalá de Henares) or Genetics and Pharmacogenomics (Navarra), the contents have a marked theoretical character, little oriented to clinical practice or sanitary. Few of them address the issue of pathologies of genetic basis or preventive tools, for example, in chronic pathologies the elaboration of the family history. In other FF the Genetics subject is added ˜ the denomination of «applied to Pharmacy», although of this only It has the title, since the contents do not allow it to be considered as such. In others, such as that of Alcalá, of Genetics, Genomics, Pharmacogenomics have little, since of 22 thematic units 18 have to do with immunology, one with genomics and 2 with FG, and these are very generic. None of them address the issue of rare diseases and of orphan drugs.
Discussion. It is convenient to start the discussion referring to work by Johnson et al. in 20028 and how they approached the armed forces Americans the impact of new knowledge in Pharmacogenetics in education. In 2001, Milap C. Nahata, President of the American Association of Colleges of Pharmacy (AACP), by virtue of its statutes and in a necessary effort to prepare universities to anticipate and respond to the impact of emerging insights in Pharmacogenetics, Pharmacogenomics, Proteomics and Bioinformatics, requested the Academic Affairs Committee to answered the following questions: --- How will the GF change the practice of Pharmacy? --- In what period would the impact of Pharmacogenomics be seen in pharmaceutical practice? --- How can pharmaceutical education respond to the light of the evolution of this knowledge base and meet the needs of system professionals health and society?
Urging him to establish a series of recommendations. This AACP committee identified the need to include contained in FG in the Pharmacy curriculum since: «the most drug effects are determined by the interrelation of several gene products that govern the pharmacokinetics and pharmacodynamics of the medication ”. The Committee believed that Pharmacogenomics would change pharmaceutical practice with the use of the patient's genotype to guide dosing decisions, in order to improve the efficacy of medication and reduce toxicity. Defining in this work the «Competences in Pharmacogenetics and Pharmacogenomics for pharmacists ».
At this point the White Book of the title of Degree in Pharmacy in 20059, funded by ANECA. On what refers to the classification of the study subjects contained in the guidelines of the year˜90 (p. 209, table 56), in which the thematic areas of the degree are collected and in the that neither Genetics nor Pharmacogenetics are incorporated, despite reports such as those of the WHO10,11 and the abundant scientific literature published in the 1990-2000 decade on the results, progress and applications of the Project Human Genome12,13. Without this knowledge, it is evident that the general objectives could not and cannot be met and specific, and the competences of the Pharmacy degree in Spain, which are included in the aforementioned White Paper.
Latif and McKay14 were the first to evaluate, in 2004, the depth and breadth of the contents in pharmacogenetics and GF that were taught ˜ in the FF of the States United. Your work was started as a result of the document distributed by the National Coalition for Health Professional Education in Genetics (NCHPEG) and the recommendations in 2001-2002 of the Academic Affairs Committee of the AACP on «Essential basic competences in Genetics for all health care professionals. Latif and McKay conclude by stating that there was a conscience about the need to increase teaching levels in these areas in the FF.
Subsequently, in 2010, Murphy et al.15 published the results of a study on 109 faculties of States States, of which 90 (82.6%) answered, of evaluation of the breadth, depth and perceived importance of teaching in FG and the level of development in this area of the FF. and 69 faculties (89.3%) included Pharmacogenomics in the undergraduate curriculum, compared to 16 (39%) in Latif and McKay's previous study.
In the studies by Latif and McKay, the coverage of the subject varied from> 10 h in 28 (40.60%), between 10-30 h in 29 (42%) and between 31-60 h in 10 (14.5%). Almost 50% of (46.7%) were planning to increase the load of work for the next 3 years. ˜ There was a general consensus in the armed forces who responded saying that: «the teaching of the FG was becoming increasingly important in the pharmacy practice ”.
Although precise comparisons cannot be made, given that the studies analyzed in the United States refer to the year˜ 2010 and the one carried out in Spain˜ refers to 2015, It can be concluded that 5 years ago ˜ the GFR was present in universities in the United States, in a number more than 3 times higher than the Spanish ones ˜ today; this is 89.3% compared to 26.1%. At this time possibly this difference is greater given the opinion they had of increasing the presence Of the mattery.
It is noteworthy ˜ that those FF in our country that offer a greater number of places and, therefore, generate a greater number of graduates, that is, in the FF of the Complutense of Madrid, General Studies of Valencia, Basque Country, Barcelona, Santiago, Granada and Seville, neither the Genetics or FG subject.
Annex 1 reflects what, according to our knowledge and experience, should constitute the basic nucleus of the subject in its theoretical contents and that every Pharmacy student should know. It articulates in 7 major topics, namely: a) Bases of pharmacogenomic knowledge; b) Analysis and research techniques; c) Clinical pharmacogenomics; d) Pharmacogenomics and rare diseases-orphan drugs; e) Nutrigenomics; F) Radiogenomics, and g) Tools for implementation.
Extension: when evaluating the temporary needs required to teach it, it is verified that the students of medical schools dedicate 12 ECTS to the subject of Anatomy, whether or not they are going to Surgery or any other specialty in which it is basic knowledge of "anatomical entities", a total of 931 (bones, muscles, organs, vessels, etc.). So how much time should be devoted to the knowledge of 23,500 «Anatomical units of the genome», that is, of those responsible for the training, development and operation Physiological and pathological of the human being16,17. Making a reductionist approach, if one of the keys to The action of the F or the doctor is the use of pharmacological therapies, the genetic bases responsible for their The answer is at least 925 genes, therefore, at least in Each of the 2 degrees, Pharmacy and Medicine, should dedicate at least 12 ECTS to GF, which is far from the 3-6 ECTS that the FF that teach it dedicate in the present.
Other aspects that are deemed necessary to reflect for that serve as reflection are: the subject of diseases rare and orphan drugs and practical contents: clinical, analytical and experimental, master's degrees, specialization and continuous training in Hospital Pharmacy, Primary and Community Care.
A strategy of interest regarding the convenience of standardizing and promoting the incorporation of content in university education at the national level is the one referred to by Lee et al.18 of constituting a group of teacher educators trainers to create content, introduce it, follow it, update and evaluate its implementation, which was developed in 2009 by the Skaggs School of Pharmacy and Sciences Pharmaceuticals from the San Diego University of California with 208 A. Corno Caparrós et al. funds from the Centers of Disease Control and Prevention, developing evidence-based educational material to through a program called Pharmacogenomics Education Program (PharmGenEd): Bridging the Gap between Science and Practice19, aimed at licensed clinicians and for students in the health professions. Its objective: increase awareness and knowledge about the validity, usefulness and potential benefits and harms of the pharmacogenetic tests. This curriculum focuses on those therapeutic areas in which pharmacogenetic testing can be applied.
It is considered necessary following innovation strategies, developed in other countries, the formation of a specially trained team of hospital Fs with clinical experience that allow the situation to change current in our country. Already forming hospitable F, from Primary and Community Care, and specialist doctors and Primary Care.
It is not among the objectives of this article to analyze the situation of the teaching of GFR and Genetics in the Spanish medical schools; ˜ yes comment that In PubMed and Google schoolar there is no reference on the subject, it does refer to other countries, such as States States, Israel, England and Southern European countries in the works by Skirton et al. (2010), Gurwitz et al. (2003 and 2005), Green et al. (2010), Higgs et al. (2008) and Pisanu et al. (2014) 20-26. In the work of Skirton et al. referring to European countries and genetics, there is a need for a minimum common standard for all healthcare professionals. A work that offers a recent overview in 2010 and next in relation to GFR is that of Green et al.20. The author's conclusion is that 'most schools of Medicine in the USA and Canada have begun to incorporate FG content in the curriculum; however, the extent of education ˜ is lower than in Pharmacy-USA schools. To adequately prepare physicians for practice in the era of personalized medicine, schools of Medicine should be encouraged to incorporate a greater content in FG on your resume. The article is relevant de Collins (1999) 13, director of the NIH, «Avoiding losses in the genetic revolution. The urgent need to educate the doctors in genetics ». The author states that there is a lack of knowledge because doctors in practice have not received a university education or professional as continuing training in Genetics.
The delay in our faculties is not without costs human and economic. Clear consequences are evident in the socio-sanitary report on Rare Diseases, ENSERio-200927, which reflects, for example, that the average diagnostic delay in these pathologies is of 5 years ˜ and in one of every 5 affected the delay is 10 or more years. For a population of 787,007-839,648 affected.
In our country, according to the work of Antonanzas ˜ Villar30 In the area of «non-safety», the one in which the most research has been carried out is that related to drugs31. By applying the top-down approach of the System National Health Office, it was estimated, referring to 2011, that there would have been There have been 240,000 admissions for adverse effects of the medication, which would mean about 912 million, with a cost unit of 3,800 euros. Not taking into account intangible costs, such as pain, patient anxiety affected or the repercuss ons on the health status of the patients who have presented the consequences of not system security. Extrapolating the indices of work Ingelman-Sundberg16, pharmacogenetics would avoid between 60,000 and 144,000 of these income due to adverse effects.
It can be concluded that the majority of undergraduate students from the Armed Forces of our country go out to exercise professional in the 21st century with little scientific background, experimental-analytical and socio-sanitary in some subjects which should already constitute an important axis of the profession today. We trust that this work contributes not only to reflection, but to the decision-making of the actors responsible, and to correct diligently and effectively the situation for the benefit of the population of our country, to the they should serve.
Conflict of interests.
The authors declare that they have no conflict of interest.
Anexo 1. Contenidos básicos teóricos de la
FG. Dr. A. Corno, agosto del 2016.
Annex 1. Theoretical basic contents of the Pharmacogenomics-Pharmacogenetics subject FG. Dr. A. Corno, August 2016. A. Bases of pharmacogenomic knowledge --- Pharmacogenes Phase I --- Pharmacogenes Phase II --- Phase III Pharmacogenes. SLC and ABC genes --- Phase IV Pharmacogenes. Nuclear receptors --- Pharmacogenes therapeutic targets --- Pharmacoepigenetics --- Pharmacogenes and adverse effects --- Pharmacogenomics and patient stratification --- Chronopharmacology. Molecular genetics of clocks circadians --- Endophenotypes. Stratification of patients. Standardization of CTCAE terms. Common criteria. Adverse Effects Terminology
B. Analysis and research techniques --- Analytical techniques in clinical pharmacogenomics and investigation. Genotyping, sequencing, arrays, ADME. Expression studies. QA. Pharmacogenetic laboratory implementation --- Drug selection algorithms based on genotypes C. Clinical pharmacogenomics --- Pharmacogenomics in oncology --- Pharmacogenomics in cardiology --- Pharmacogenomics in psychiatry --- Pharmacogenomics in diabetes --- Pharmacogenomics in the treatment of pathologies neurodegenerative --- Pharmacogenomics in the treatment of drug addictions tobacco, alcohol and illegal drugs --- Pharmacogenomics in pain treatment --- Pharmacogenomics in dermatology --- Pharmacogenomics in urology --- Pharmacogenomics in pulmonology-asthma, COPD --- Pharmacogenomics in Infectious Diseases Teaching ˜ Pharmacogenetics in Faculties of Pharmacy 209 --- New gene-based therapies: gene therapy, optogenetics, DNA drugs, mitochondrial therapies D. Pharmacogenomics and rare diseases. Medicines orphans E. Nutrigenomics --- Genetic variability and individual needs of nutrients, micronutrients and phytonutrients --- Nutrigenomics in oncology --- Nutrigenomics in neurodegeneration --- Nutrigenomics in diabetes --- Nutrigenomics in cardiovascular diseases F. Radiogenomics G. Tools for implementation --- Family history in Pharmacy: prevention and risk assessment tool --- Statistical tools for the analysis of interactions: genes-genes, genes-environment --- Bioinformatics tools. Databases of usefulness in clinical pharmacogenetics. PharmGkb, DrugBank, OMIM, Functional SNP Prediction --- International working groups on Pharmacogenetics --- Implementation models in Hospital Pharmacy and Community --- Information and communication. New technologies
Andrés Corno Caparrós a, ∗, Pedro García Salomb and Amparo Soria Aledoc a Genetic Analysis ANCOR, Alicante, Spain˜ b Hospital Vega Baja-Alicante, Associate Professor UMH, Pharmacy and Pharmaceutical Technology, Alicante, Spain c Orihuela-Alicante Health Department, Associate Professor UMH, Business Organization Received October 10, 2016; accepted March 29, 2017. Available online June 2, 2017.