Students' knowledge and views on pharmacogenomic education in the medical curriculum.

INTRODUCTION: Pharmacogenomics is a growing field of science that explores the genetic contributions in an individual's response to the drug, so as to choose the right drug in the right doses tailored to a patient's genetic makeup. Although pharmacogenomics information is incorporated in chapters discussing relevant drugs, it has not been materialized into clinical practice yet and still, it remains a challenge due to limited knowledge and accessibility of the pharmacogenomic tests to diagnose these polymorphisms. With this background, the objective of the study was to assess the knowledge and perception of pharmacogenomics among second-year MBBS students and to sensitize them regarding pharmacogenomics.
MATERIALS AND METHODS: A cross-sectional study was done in which 138 medical students responded to a preformed semi-structured assessment tool. It comprised two main components (1) knowledge and (2) relevance of pharmacogenomics in medical education and clinical practice.
RESULTS: Ninety-five percent students defined pharmacogenomics correctly, but only 54% were aware of genetic variations in drug targets, metabolizing enzymes, and transporters affecting drug therapy. Only 15% knew about the availability of pharmacogenomics tests in India. Eighty-four percent of students felt that incorporating pharmacogenomics education in the MBBS curriculum is a must for precision medicine.
CONCLUSION: Second-year MBBS students had good knowledge of pharmacogenomics, but knowledge about the application in clinical practice and interpretation of pharmacogenomics was limited. Therefore, we recommend (1) basic pharmacogenomic education at all levels of medical curricula, (2) development of case-based knowledge application modules, (3) regular continuing medical education to update about available screening tools/biomarkers, and (4) patient and public awareness programs so that they receive personalized/precision medicine with optimum efficacy and reduced side effects and health-care costs.

Introduction

Current concepts in drug therapy often attempt drug treatment of large patient populations as groups, “one size fits all” approach to drug prescription and dosing, irrespective of their individual genetic differences in drug response.[1] Approximately 25%–60% of patients respond positively to their medications, but the remaining fraction suffers from significant therapeutic delays due to pharmacogenomic variations.[2] This increases the incidence of adverse drug reactions (ADRs), which prolongs hospital stay and is the sixth leading cause of death in the world.[23] Pharmacogenomics is a growing field of science that explores genetic contributions in an individual's response to drugs.[4]

Pharmacogenetics refers to “monogenetic variants” affecting drug response, whereas pharmacogenomics refers to the “entire spectrum of genes (genome)” which can influence drug efficacy and safety. However, both the terms are used interchangeably.[5] It combines the knowledge of drug pharmacokinetics and pharmacodynamics with modern genetic testing to provide a comprehensive view of the response of a particular patient to specific drug therapy. Therefore, proper education and training in this specialty will guide to practice personalized medicine to optimize drug efficacy, prevent toxicity, and reduce the overall economic burden to the health-care system.[4] The Human Genome Project in 2003 threw open the doors to pharmacogenomics exploration worldwide.[6] Delay in translating this knowledge into clinical practice relates to the fact that an individual's response to drugs is multifactorial, resulting from multiple genes and environmental interactions and nonavailability of facilities for genetic testing.[7]

Genetic variations can result from single-nucleotide polymorphism (SNP), insertion, deletion, or duplication of DNA sequences. SNP is probably the most common variation. Polymorphisms in the drug metabolizing enzymes are the first recognized and[8] clinically relevant examples are (1) Thiopurine S-methyltransferase (TPMT) -deficient patients on mercaptopurine experience severe myelosuppression and dose reduction is recommended[9] and (2) patients receiving carbamazepine who test positive for HLA-B*1502 allele are at higher risk of Steven–Johnson syndrome and toxic epidermal necrolysis.[1011] The United States Food and Drug Administration (FDA) further strengthen the role of pharmacogenomics in clinical practice by changing the drug labeling of drugs such as warfarin, clopidogrel, and aripiprazole requiring testing for CYP2C9, CYP2C19, and CYP2D6 polymorphism, respectively.[1213] Pharmacogenomics testing requirements are mentioned in more than 100 medications drug labels, such as trastuzumab, cetuximab, maraviroc, and dasatinib and “highly recommended” testing for abacavir, carbamazepine, irinotecan, and mercaptopurine.[14]

Indian population is extremely diversified by their genetic constitution, language, religion, and sociocultural characteristics. These differences make them a unique resource for pharmacogenomics heterogeneity compared to the rest of the world.[15] Chhattisgarh (Central India) population is made of multiple ethnic groups, and a study shows that G6PD deficiency varies from 13.0% to 21.3% in the Gond tribal population of this area compared to 2.3%–27.0% in India.[16] The inclusion of pharmacogenomics in health-care delivery poses many challenges: like defining candidate gene and drug, choosing relevant biomarkers, their accessibility in the stipulated time period, interpretation of results, and cost-effectiveness.[17]

Therefore, sensitizing medical students about the need of pharmacogenomics education in medical institutions is the need of the hour. In response to the growing need, various international organizations have taken the initiative to incorporate standard pharmacogenomic education in medical, pharmacy, and public health schools.[18] In 2005, the International Society of Pharmacogenomics (ISP) made recommendations for undergraduate medical teaching in pharmacogenomics.[19] With this background, we did this study to assess second-year MBBS student's knowledge and views on the importance and relevance of pharmacogenomics in the medical curriculum, with the aim to sensitize them as well as to get their views so that they can apply this evolving science into practice to optimize treatment.

Materials and Methods

Study design

A cross-sectional study design was conducted in which a structured assessment tool was used by the Department of Pharmacology, Pt J N M Medical College, Raipur.

Study period

This study was conducted in May 2017.

Sample size

The study population was second-year MBBS students. One hundred sixty students were enrolled in the class, and on the day of the data collection, 138 students were present in the class. Verbal consents were obtained, and those unwilling to participate in the survey were given the option not to participate, but all 138 students consented to participate. The purpose of this study was explained, and they were instructed to answer questions sincerely. Confidentiality was assured. The assessment tool was filled in the presence of departmental faculty.

Data collection tool

A preformed, semi-structured questionnaire based on our study objectives was developed based on the previous literature[14171920] and reviewed by departmental faculty. It was pilot tested among the postgraduate students of the department and subsequently modified. The final questionnaire consisted of 20 questions: question no 2 was open ended and the remaining were closed ended. Closed-ended questions were on 3-point Likert scale format, and it took 20 min to fill the questionnaire [Annexure 1].

Statistical analysis

Statistical analysis was done using descriptive statistics and nonparametric test (Chi-square test) for proportionality using IBM SPSS version 20 IBM Director of Licensing, IBM Corporation, North Castle Drive, Armonk, NY 10504-1785, U.S.A.

Ethical Justification

The Institutional Ethics Committee permission was obtained prior to the initiation of the study.

Results

All 138 students had completed and returned the questionnaires of which 110 students had heard about pharmacogenetics/genomics and were included in the study, 59% were male and 41% were female. In terms of gender, the knowledge and relevance scores were statistically not significant (P > 0.5). A majority (80%) of the students had heard the words pharmacogenomics and personalized medicine from textbooks and the Internet [Figure 1]. Fifty-four percent of students defined pharmacogenomics and personalized medicine correctly.

Figure 1

Source of pharmacogenomics information

In response to questions on Knowledge of pharmacogenomics [Table 1] 95% of students knew that pharmacogenomics is the study of drug response in relation to human genetic variations and 90% understood its role in drug safety, but only 54% of students knew that genetic variations in drug targets, metabolizing enzymes, and transporters affect drug therapy. Only 43% had knowledge about the relation of responsiveness of trastuzumab and human epidermal growth factor receptor 2 (HER2) receptor and 40% knew that genetic variations affect the toxicity of isoniazid. Eighty prercent of students knew that genetic variations influence the incidence of hemolytic anemia in G6PD-deficient people.

Table 1

Knowledge of pharmacogenomics

Questions	Number of students (n=110)
	Yes (%)	No (%)	No idea (%)
Pharmacogenomics is the study of drug responses in relation to human genetic variations	95	3	2
Pharmacogenomics aims at understanding the roles of human genetic variations in drugs safety	90	1	9
Genetic variations in drug targets, metabolizing enzymes, and transporters affect drug therapy	54	5	41
Trastuzumab responsiveness is due to genetic variations in HER2 receptor	43	11	46
Genetic variations affect pharmacological action of isoniazid	40	7	53
Genetic variations influence the hemolytic anemia in G6PD deficient people	80	3	17

HER2=Human epidermal growth factor receptor 2

When asked about the relation of pharmacogenomics to pharmacovigilance and drug development, 46% said that knowledge of pharmacogenomics is likely to decrease the number of ADR and 68% had no idea if pharmacogenomics would decrease the cost of developing drugs, as shown in Table 2. Student's opinions were taken on the relevance of knowledge of pharmacogenomics where 84% thought that pharmacogenomics is relevant to the medical profession and 82% wanted it to be included in the MBBS curriculum. Ninety-three percent felt that it is relevant in patients' diagnosis and treatment and 84% felt that it should be linked to the pharmacovigilance program to reduce ADRs. Eighty-one percent of students said that pharmacogenomic testing is not for sick people only and 47% thought that using pharmacogenomics in practice will increase health-care costs [Table 2]. Almost 82% of respondents had no idea about the availability of pharmacogenomics testing in India [Figure 2]. Only 68% were willing to have their own pharmacogenomics profile. Only 58% of students know that genetic information is now a requirement for some drug labels, according to the FDA [Figure 3]. Test for proportionality has been applied to check if there is any statistical difference between correct and incorrect responses for knowledge and relevance. Test for proportionality had been applied and it was observed that statistically significant number of studentshad adequate information regarding pharmacogenomics and it's relevance and importance in health care.

Table 2

Importance and relevance of knowledge of pharmacogenomics

Questions	Number of students (n=110)
	Yes (%)	No (%)	No idea (%)
Is the knowledge of pharmacogenomics likely to decrease the number of ADRs?	46	47	7
Is the knowledge of Pharmacogenomics likely to decrease the cost of developing drugs?	16	16	68
Is pharmacogenomics relevant to your profession	84	5	11
Should pharmacogenomics education included in your MBBS curriculum	82	7	11
Should Pharmacogenomics be part of diagnosis and treatment	93	3	4
Pharmacovigilance and pharmacogenomics should be linked together for better drug safety	84	3	13
Is pharmacogenomic testing only for sick people?	1	81	18
Using pharmacogenomics in practice will increase health care costs	47	16	37

ADRs=Adverse drug reactions

Figure 2

Responses on availability of pharmacogenomics testing in India

Figure 3

Knowledge about Food and Drug Administration drug labeling

Discussion

Most of the students had a good knowledge of pharmacogenomics and understood the relevance with a few areas of gaps. Majority of the students were unaware of the fact that pharmacogenomic variations in drug target, metabolizing enzymes, transporters affect drug therapy. Similarly, a large number of students could not relate how pharmacogenomic knowledge would help in reducing the cost of drug development and the availability of pharmacogenomic tests in India. An Internet search did not show any study in India, showing health-care students' feedback of their views on pharmacogenomics and its incorporation in medical education. Textbook followed by the Internet is the source of knowledge about pharmacogenomics. A similar study done in the USA shows that only 15.9% of medical students agreed that pharmacogenomics had been a part of their curriculum,[4] whereas a study done in Ghana revealed that doctors had heard the term from colleagues followed by Internet and medical schools.[17] Fifty-four percent of students were able to define the terms pharmacogenomics and personalized medicine correctly, in spite of the fact that this topic was mentioned during the general pharmacology lectures. ISP education forum has recommended a minimum of 4 h of undergraduate pharmacogenomics teaching to medical students in 2005 by incorporating it in core pharmacology curriculum, in the education of physicians, pharmacists, and nurses to emphasize upon the significance of this rapidly evolving topic.[18] This can be incorporated as case-based learning, citing common examples of a polymorphism affecting pharmacodynamic and pharmacokinetics frequently and conducting continuing medical education (CME) in hospitals. They also called upon the publishers of pharmacology textbooks to dedicate a separate chapter on pharmacogenomics and pharmaceutical industry to develop tools for web-based learning.[21]

Maximum students could recognize the role of pharmacogenomics in drug safety which is similar to a study conducted in Malaysia where 95% of students knew that PG aims at understanding the roles of human genetic variations in drug safety.[22] Guideline for the use of pharmacogenomics in the pharmacovigilance states that “it is desirable to have data regarding relevant genomic biomarkers relating to efficacy and safety of a new medicinal product, including patient selection or dose specification at the time of approval so as to reduce ADRs.”[23] Students awareness about G6PD deficiency and resulting hemolysis is because of (a) its association with commonly used drugs such as co-trimoxazole, fluoroquinolones, dapsone, (b) endemicity of Malaria in our state and use of primaquine, and (c) high prevalence of G6PD deficiency in this area.[16] Only 5% of students felt that pharmacogenomics should not be a part of their curriculum similar to a study[4] where only 2.9% of students disagreed on this proposed curriculum expansion. They might have felt that this will increase their study burden, or they may be having a lack of confidence and awareness about the relevance of pharmacogenomics in clinical practice. In another study, 96.9% of medical doctors agreed that students should be equipped with pharmacogenomics information.[17] Majority of UK medical schools included 1–2 h of pharmacogenomic teaching in the curriculum.[14] Fifty-three percent of students felt that pharmacogenomics information is likely to decrease the number of ADRs, and this information must be linked to pharmacovigilance for better drug safety. Sixty-eight percent felt that knowledge of Pharmacogenomics will decrease the cost of developing drugs. In the process of drug discovery, many drugs fail to emerge as therapeutic agents due to failure of efficacy or appearance of ADR, leading to termination of clinical trial and incurring financial loss to the pharmaceutical company.

Fifty-seven percent students were aware of genetics information as a requirement for some drug labels according to the FDA, which is similar to another study.[10] As of 2018, FDA has published a table of pharmacogenomic markers in drug labeling and has 362 entries, and it describes issues such as (1) variability in clinical response, (2) risk of ADRs, (3) genotype-specific dosing, and (4) polymorphic drug disposition gene.[23] Eighty-two percent of students had no idea if pharmacogenomics screening is available in India. Pharmacogenomic screening is now available in India and provided by both government institutes and private laboratories. Some of the available tests are for SNPs related to suxamethonium, 5-fluorouracil, CYP2C9 Gene screening for warfarin and HER2/neu receptor screening for trastuzumab.[24] Students were also interested in having their own pharmacogenomics profile and would volunteer for personal pharmacogenetics testing if given an opportunity which is similar to study done by Surofchy et al where 59.8% volunteered for personal pharmacogenetic testing.[25]

Conclusion

Students had good knowledge and interest of pharmacogenomics in general, but knowledge about the application and interpretation of pharmacogenomics was limited. With scientific evolution in technology and understanding of the human genome, availability of easy to use, cost-effective, reliable to interpret tools/biomarkers will culminate this knowledge in treatment with optimum efficacy, minimum toxicity, and affordable health-care costs. Thus, we recommend (1) basic pharmacogenomic education at all levels of medical curricula, (2) development of case-based knowledge application modules, (3) regular CME to update about available screening tools/biomarkers, and (4) patient and public awareness programs so that the clinician is confident and patients assured that they are on the path of precision medicine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.