1. Introduction
Pharmacogenomics is the study of the relationship between genetic biomarkers and variation of individual drug response, metabolism, and transport. The application of clinical pharmacogenomics can provide a patient-personalized approach to drug therapy by using genetic information to guide drug dosing and selection. Using patient pharmacogenetic information, healthcare providers can choose drugs that are more likely to be efficacious, avoid side effects, optimize patient-specific doses, and/or determine the need for closer monitoring. The US Food and Drug Administration lists more than 140 therapeutic products with pharmacogenomic information in which specific action could be taken based on biomarker information [
1]. Various evidence-based, peer-reviewed guidelines on clinical pharmacogenomics [
2,
3] also exist to assist health providers in patient drug management. As the most accessible healthcare providers and medication experts, pharmacists are well-suited to direct and deliver pharmacogenomics-based patient care [
4,
5,
6,
7].
Substantial scientific progress has been made in the understanding between genetic variation and variability of drug response and effect; however, pharmacogenomic testing has not been fully implemented in clinical practice. Potential barriers include cost-effectiveness and reimbursement, ethical concerns, and required educational and equipment infrastructure. Healthcare professionals, including pharmacists, report a lack of confidence in applying clinical pharmacogenomics despite the belief that it is important [
4,
8]. Opportunities to improve patient care based on pharmacogenomic-guided recommendations are missed due to insufficient clinical training and knowledge of how to translate genetic test results into clinical action based on currently available evidence. While 92% of US pharmacy schools have incorporated pharmacogenomics into their curricula [
9], only 17% of practicing pharmacists reported their understanding of pharmacogenomics as “excellent”, “very good”, or “good” [
10]. This knowledge gap is a significant barrier to widespread implementation of pharmacogenomic-based medicine, and exposing student pharmacists early in the curriculum with in-depth education and hands-on application of pharmacogenomics may further increase student comfort and foster a positive perspective towards pharmacogenomics [
11,
12]. Established core competencies outlined by the American Association of Colleges of Pharmacy (AACP) [
13], Genetics/Genomics Competency Center (G2C2) [
14] and the 2014 American Society of Health-System Pharmacists (ASHP) statement address the fundamental responsibility pharmacists have to ensure pharmacogenomics testing is performed as needed and that results are used for medication therapy optimization [
15]. These competencies may help strengthen the focus of pharmacogenomic education in Doctor of Pharmacy (PharmD) program curricula and advance the role of the profession.
The purpose of this study was to evaluate the impact of an educational intervention including personal genotyping on student pharmacists’ attitudes and self-efficacy towards clinical pharmacogenomics. This study was a continuation of a previous study [
16] and combines the results of both years. It was hypothesized that personalized genotyping would lead to more real-life understanding of the benefits of personal genomics and clinical acceptance.
2. Materials and Methods
Subjects included two classes of second-year pharmacy students attending the UNC Eshelman School of Pharmacy during Spring 2015 and Spring 2016 semesters. The student cohort included individuals from Chapel Hill and satellite Asheville campuses enrolled in a 15-week course designated as Pharmaceutical Care Lab (PCL), which was required as part of the PharmD curriculum. This lab-based course allowed students the opportunity to practice communication and develop competencies in skills (e.g., compounding, medication and drug-delivery device counseling and demonstration, and completion of patient cases). Students provided informed consent to participate in this study; participation was voluntary and did not influence their coursework grade. The UNC Institutional Review Board determined that this study was exempt from review.
The PCL consisted of a once weekly 1-h large group lecture with attendance from all second-year pharmacy students and weekly 4-h small group sessions consisting of 8–10 students per group. All students were led by clinical laboratory instructors (e.g., pharmacy residents and clinicians) in the large and small group sessions. These instructors were all practicing pharmacists but had various backgrounds in terms of practice setting (e.g., community, ambulatory care, and hospital) and previous exposure to and interest in pharmacogenomics. None of the instructors had specialized training in pharmacogenomics (e.g., pharmacogenomics residency or certificate program).
Educational intervention materials consisted of (1) a PowerPoint presentation with background information about pharmacogenomics; (2) an evidence-based educational video through 23andMe to help students understand basic methodologies employed in pharmacogenomics tests; (3) a demonstration to guide students through the logistics of sample acquisition; and (4) a pre-testing consultation using the 23andMe platform during a large class session on week 8 of the course. On week 11 in small group sessions, students received (5) small group case reviews with hands-on training for managing drug therapies based on the pharmacogenomic results from a demo 23andMe test and (6) exposure to real-world patient case scenarios through various counseling exercises. Further details describing the timing of the various components of the educational intervention are described in
Appendix A.
An anonymous electronic survey was administered during week 8 of the PCL course before the introductory pharmacogenomic presentation. The same survey was conducted with additional questions upon completion of the pharmacogenomic lecture series in week 15 with discussion of how to interpret their personal 23andMe results in a large class session. The survey was adopted from prior published surveys on medical and graduate students’ attitudes towards genomics and personalized medicine [
17,
18,
19] and modified to target student pharmacists. The survey gathered student demographics and assessed enrollment in previous genetics courses. Additionally, the survey assessed student pharmacists’ professional and personal attitudes and self-efficacy related to clinical pharmacogenomics and personalized genome testing. Survey questions prompted individuals to respond to their level of agreement with statements using a five-point Likert scale (i.e., strongly agree, agree, neither agree nor disagree, disagree, and strongly disagree), yes/no, or yes/no/maybe answers. Survey responses were linked using the same alphanumeric code for the pre- and post-intervention surveys to maintain student anonymity.
The pharmacy students were offered voluntary personal genomic testing by the direct-to-consumer 23andMe test (Mountain View, CA, USA) at a discounted price of $30.00. Funding from the UNC Center for Pharmacogenomics and Individualized Therapy (CPIT) was provided. Students were informed about the nature of their participation, including personal health information and potential risks beforehand. Willing participants could obtain the 23andMe test on campus or online and ship his/her saliva samples directly to 23andMe with a prepaid shipping label. The results of the 23andMe genotype test were delivered within 4–8 weeks (prior to the completion of the PCL course) through a free online 23andMe account to be accessed solely by the student for personal use. 23andMe provided participants with limited information regarding ancestry, carrier status, and genetic variability from the Illumina OmniExpress 23andMe v4 chip consisting of approximately 570,000 markers (San Diego, CA, USA). Students were instructed regarding use of the 23andMe website, including how to download raw data, but were also provided with demo profile information in case they opted out of the testing process. Because 23andMe presents results on a limited number of genes related to health, student pharmacists were referred to additional websites for detailed health information and provided with precautions and limitations of utilizing various online resources. The 23andMe test results were not directly linked to pharmacogenes; therefore, student pharmacists also had the option of extracting personal pharmacogenomic data from the 23andMe raw genotype file with a data-processing Excel spreadsheet developed by our lab using gene haplotype translation tables from PharmGKB for CYP2C19, CYP2C9, CYP3A5, CYP2D6, DPYD, TPMT, G6PD, IFNL3, SLCO1B1, and VKORC1. The data could be interpreted by using hyperlinked Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines within the spreadsheet. None of the individual pharmacogenomic results from the 23andMe tests were accessed, collected, or used in any of the teaching materials or for any research purpose.
Responses from the pre-intervention survey were collected for all student pharmacists to assess initial attitudes towards clinical pharmacogenomics. Data from students who completed both the pre- and post- intervention surveys was analyzed in a paired subset group and further delineated between those who underwent personal genotyping versus those who did not undergo personal genotyping. Students who responded to at least 70% of both the pre- and post-survey questions were included in the paired subset. McNemar’s test and the Wilcoxon signed rank test were used to analyze paired pre- and post-intervention survey responses respectively for binary comparisons and Likert items. Fisher’s exact test and the Mann Whitney-U test were used to analyze responses between genotyped and non-genotyped students respectively for binary comparisons and Likert items. Results were considered statistically significant if p < 0.05.
4. Discussion
As pharmacy schools are the leaders and innovators that drive pharmacy practice forward, educational interventions should have a positive and beneficial impact to shape student thoughts and impressions of pharmacogenomics that will ultimately be carried with them into clinical practice. Because the implementation of pharmacogenomics is coming to fruition in the clinical setting [
20,
21,
22,
23,
24,
25,
26,
27,
28], pharmacogenomics should be added to pharmacy school curricula. Education in pharmacogenomics helps pharmacy students understand the clinical utility and application of pharmacogenomics-guided therapeutic drug selection and adjustment. The educational intervention provided in this study was designed to make learning pharmacogenomics more engaging and experiential. Students demonstrated a significant increase in their confidence in applying clinical pharmacogenomic information and knowledge of clinical resources to manage patients’ drug therapy and were more likely to recommend personal genotyping for a patient.
This study was beneficial in demonstrating that pharmacogenomic educational interventions can make a difference to student attitudes in a way that could eventually lead to more acceptance of clinical pharmacogenomics in practice despite limitations. Limitations of this study include lack of a testing component to assess objective learning competencies. There was also a relatively low response rate due to optional survey participation, which may have introduced selection bias. This limitation may also be compounded by the evolution of the survey instrument. Originally adapted from Salari et al. [
17,
18], the survey instrument to assess attitudes and confidence had slight changes from year 1 to year 2 (e.g., additional items were added). These changes do provide us with additional insight into personalized genotyping, particularly as future studies will incorporate alternative assays focusing solely on pharmacogenes.
Additional schools of pharmacy are implementing personalized genotyping into the curriculum. Weitzel et al. introduced personalized genotyping into a pharmacogenomics elective [
29]. Adams et al. described an initiative termed “Test2Learn” using 23andMe as their genotyping platform [
30]. Most students felt pharmacogenotyping was an important part of the course and felt they had a better understanding of pharmacogenomics because of the genotyping activity. There are also limitations in personalized genotyping with 23andMe, as information on specific pharmacogenes is not readily available or interpretable. Future studies will examine the use of in-house next-generation sequencing assays that selectively examine pharmacogenes in the education of student pharmacists. Next-generation sequencing may provide some benefits compared to 23andMe in terms of potentially lower costs, greater flexibility, faster turnaround time to obtaining results, and more autonomy with an in-house assay compared to the use of a larger commercial company. With a next-generation sequencing assay, analysis of only pharmacogenes can occur, rather than examining genetic variants related to disease state and ancestry, in order to reduce ethical conundrums and enhance the relevance of the exercise to future pharmacists.
The study described here largely adhered to educating students on existing pharmacogenomics guidelines and applications. However, personalized medicine continues to transform practice. In the future, we may introduce additional facets of personalized medicine beyond pharmacokinetics, pharmacodynamics, and pharmacogenomics, including the effects of additional systems such as the microbiome and circadian rhythm [
31,
32,
33]. As pharmacogenomic testing services become increasingly available to patients, either through healthcare providers or direct-to-consumer routes, there is more opportunity for pharmacists to provide pharmacogenomic counseling as an extension of medication-therapy-management (MTM) services. Pharmacists are ideally equipped to evaluate medication therapy challenges and implement solutions based on evidence-based precision medicine research. Effective pharmacogenomic educational interventions in PharmD curriculums can help pharmacy students better understand what a patient’s personal genotyping experience might be like and empower them to implement these valuable clinical services in their practice as future pharmacists.