A Survey of the UK Pharmacy Profession’s Educational Needs on Pharmacogenomics

Objective . Te aim of this exploratory study was to ascertain the current educational status of pharmacogenomics (PGx) within the present and future UK pharmacy profession, in addition to ascertaining future educational and infrastructure needs of pharmacists to adopt PGx into practice. Methods . A 35-question survey was sent electronically to practicing pharmacists, pre-registration pharmacists, and Master of Pharmacy (MPharm) students throughout the UK between April 2018 and May 2019. Responses were anonymous and analysed using GraphPad Prism 8 and SPSS statistics 26. Results . In total, 264 participants, where data could be used for analysis, responded to the survey. Tis comprised 196 practicing pharmacists and 68 preregistration pharmacists/MPharm students. Te fndings demonstrated variation in undergraduate level exposure to PGx between those who had qualifed within the past 10years and those who had qualifed over 10years ago. Over 60% of qualifed pharmacists did not feel confdent in identifying drugs that require PGx testing. Nearly three quarters of respondents cited that PGx guidelines were needed to help facilitate a PGx service, although 63.6% also stated that they had previously never looked for a PGx recommendation. Most respondents cited PGx as a low or medium learning priority. Conclusion . Our survey suggests that further education is required to prepare the UK pharmacy workforce for the advent of PGx. A focus on the provision of, and education around, PGx guidelines is needed. In addition, the disparity identifed between pharmacists at diferent stages of their career will need to be addressed with tailored and targeted educational packages.


Introduction
Pharmacogenomics (PGx) refers to genetic variation in drug response (efcacy and safety) and was frst coined by geneticist Friedrich Vogel in 1959 [1]. Te terms pharmacogenomics and pharmacogenetics are often used interchangeably within the literature. Te science of PGx has been extensively studied with an increasing number of publications since the completion of the human genome project, and greater emphasis on implementation of pharmacogenomics into clinical practice.
Current estimates indicate that around 98-99% of people carry a pharmacogenetic variant [2]. Te presence of such a variant, termed a genetic polymorphism [3] if found at a frequency over 1%, may have a resulting impact on the pharmacokinetics (PK) or pharmacodynamics (PD) of a medication resulting in the potential for an inefective treatment or adverse drug reaction (ADR).
Te efectiveness of PGx testing in determining and reducing the incidence of ADRs for some medications has been so compelling that it has resulted in mandatory testing prior to prescribing. Perhaps the most well-known is the nucleoside reverse-transcriptase inhibitor, abacavir, used in the treatment of human immunodefciency virus (HIV). Originally, it was estimated that around 5% of patients treated with abacavir would experience hypersensitivity reactions manifested as cutaneous eruptions, lung, and gastrointestinal manifestations, which increased in reaction severity on rechallenge [4]. However, in the early 2000s, a series of studies identifed an association between abacavir hypersensitivity and the presence of the HLA-B * 57 : 01 allele [5][6][7] and an interventional trial was able to demonstrate that prescreening for HLA-B * 57 : 01 resulted in elimination of immunologically confrmed hypersensitivity reactions [5]. Tis resulted in mandatory or recommended testing instructions in the drug labels in addition to recommendations within international prescribing guidelines [8].
Despite such successes, the transition of PGx into routine clinical practice has, overall, been slow. In the UK and internationally, availability of PGx testing has remained largely in the remit of specialist care settings (e.g., HIV and cancer). However, in the past decade the landscape of PGx testing has been changing with an increasing emphasis on implementation, as well as the availability of direct-toconsumer tests (DTC) for the public.
Te aim of this exploratory study was to ascertain the current educational status of PGx within the present and future UK pharmacy profession, in addition to ascertaining future educational and infrastructure needs of pharmacists to adopt PGx into practice.

Methods
Tis study used a questionnaire-based, cross-sectional methodology to prospectively gather anonymised data from registered, preregistration, and student pharmacists in the UK. Due to the absence of any comparative UK data, an inductive research approach was adopted.
A 35-question survey was designed by a multidisciplinary team of researchers including expert PGx clinicians and a clinical pharmacist. Te survey comprised a mixture of question types including 5-point Likert scale, multiple option, and free-text questions (supplementary material (available herer)). Questions were based on other studies from the feld [9][10][11][12] covering topics including confdence and familiarity with genetics and PGx, addressing barriers to implementation, and understanding the needs surrounding further education. Testing of underlying PGx knowledge was also undertaken in the survey but is not discussed within the context of this paper. Our approach enabled respondents' opportunities to provide qualitative data on their thoughts around PGx topics in addition to the more restrictive quantitative questions.
Te survey was hosted using the website "Survey monkey," participation was voluntary and consent for involvement obtained during the frst question. Responses collected were anonymous. Whilst it was not possible to skip any questions, not all participants completed the survey and so in this instance of missing data, the "unknown" category was assigned.
Te survey went live in April 2018, and the access link was sent out nationally via "gate-keepers" (i.e., chief pharmacists or heads of pharmacy schools) into a variety of sectors of the pharmacy profession including community, hospital, and academia.
In June 2018, three months after the survey had gone live, it was noted that a high proportion of the respondents were based in hospital pharmacy. To counter this, and provide a broader perspective of the profession, the survey was further disseminated to pharmacists and pharmacy student groups using the social media platform Facebook.
Data were analysed using GraphPad Prism 8 and SPSS statistics 26, and for the purposes of the analysis, the respondents were broadly subdivided into two categories: "qualifed pharmacists" and "in training,". Tese were further subdivided into pharmacists qualifed over 10 years, less than 10 years, preregistration pharmacists, and pharmacy undergraduate students. Statistical signifcance in fndings between any two groups was assessed using the Pearson χ 2 test. Te threshold for statistical signifcance throughout this study was set at p ≤ 0.05.
An XY scatter plot was created to assess any correlation between two sets of data which had a 0-100 scoring system. Tis scatter plot was created using responses from participants who provided answers to both questions and r 2 (goodness-of-ft of simple linear regression) calculated using GraphPad Prism 8.

Ethics Statement. Te University of Liverpool Ethics
Committee approved the survey on 05/04/2018 prior to implementation of the European General Data Protection Regulation (GDPR). An amendment was submitted to include dissemination via social media on 29/06/2018 and approved on 10/07/2018.

Demographics.
A total of 268 participants commenced the survey. It was not possible to calculate an accurate denominator due to the uncertainty regarding the reach of social media and therefore it was not possible to determine response rate.
Of the respondents, one person did not complete the survey demographics, or any subsequent questions and a further three participants were registered and practicing outside the UK. Data from these individuals were not included in the analysis, leaving 264 participants eligible for analysis. 196 of these were qualifed pharmacists and 68 were considered "in-training" (preregistration or undergraduate). Full demographics of included participants are shown in Table 1.

Confdence and Familiarity with Genetics and PGx.
Over 97% of respondents in both the qualifed and intraining groups reported that they had received prior education in genetics (Question 11), but this dropped to 76.7% when asked about PGx specifcally (Question 15). Within the qualifed pharmacist group, there was a statistically significant diference between those qualifed ≤10 years and >10 years with no previous PGx education, rising from 16.9% to 30.1% respectively (Pearson χ2 = 4.71, p � 0.03).
Undergraduate studies were cited as the most common place respondents received education on both PGx and genetics (Questions 10 and 14) across both qualifed and intraining groups (as shown in Figure 1). Other 0 (0) Prefer not to say When asked if they felt confdent in their knowledge of which drugs required genetic testing prior to prescribing (Question 18), 65.3% of qualifed pharmacists and 63.3% of the in-training cohort cited "strongly disagree" or "disagree" as shown in Figure 2.

Age (years)
In addition, in response to the question "in the past 12 months, how often have you requested/recommended a pharmacogenetic test be performed?" (Question 17) 86.7% of qualifed pharmacists and 85.3% of the in-training cohort cited that they had never requested or recommended a test.
One qualifed pharmacist (0.5%) reported requesting or recommending a test over 15 times. Tis individual cited their specialism as rheumatology where drugs which require TPMT testing, such as azathioprine, are frequently used. A further 7 pharmacist respondents (3.6%) reported requesting or recommending a test 1-5 times in the preceding 12 months. Of these, 6 were practicing in an NHS hospital within specialities including critical care, respiratory, and oncology. Te fnal respondent was working as a community pharmacist.
Respondents were also asked to rate their confdence "to make/advise a drug or dose change based on a pharmacogenetic test result" using the same 0-100 scale (Question 21). Over 90% of respondents in both cohorts rated their confdence level at 50 or below.
To ascertain if confdence in knowledge translated into confdence in utilisation, an XY scatter graph was created ( Figure 3) using the self-rated confdence scores from the abovementioned question and "how confdent do you feel in your current knowledge and understanding of pharmacogenomics?" (Question 16). Te plot demonstrated a small positive correlation between the two data sets with an R 2 value of 0.23 (p � < 0.0001).
In response to the question about how many times they had "reviewed a PGx test result" (Question 20) in the past 12 months, the number of pharmacist responders who answered "never" was lower for this at 156 (91.8%) compared with 162 (95.3%) when asked about reccomending/requesting a test. Te same pharmacist who requested a test over 15 times also said they had reviewed a result over 15 times in a 12-month period.
Furthermore, respondents were asked to cite where, if applicable, they had previously searched for PGx based recommendations (Question 19). Across all respondents, 63.6% stated that they had never looked for PGx recommendations. Respondents were asked to rate their confdence in their knowledge and understanding of genetics and PGx (Questions 10 and 14) using a 0-100 scale wherein 0 equated to "not confdent" and 100 "very confdent." Te overall level of confdence was lower for PGx than genetics for all respondents; in addition, the in-training cohort demonstrated a higher average confdence level than qualifed pharmacists for both genetics and PGx. Of those who had searched for PGx recommendations, over 70% cited using more than one reference source, with the most popular choices being the British National Formulary (BNF) and the Summary of Product Characteristics (SPCs). Although overall usage of PGx specifc reference sources was low, the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines were the most utilised with 4.1% of pharmacists and 4.4% of those intraining citing this. Other sources cited included NICE guidelines, experts, and local protocols.

Barriers to PGx Implementation into Clinical Practice.
When asked if they would utilise "point of care" PGx testing if it were available (Question 23), for example in a community pharmacy, a greater number of the in-training cohort than the qualifed pharmacist cohort responded with extremely likely or likely, at 59% and 39.8%, respectively. Respondents also gave a free-text answer when asked to outline reasons why they would be likely or unlikely to utilise this technology (see Table 2).
A recurring theme in the responses related to who has responsibility for requesting a genetic test. Predominantly, the consensus from these responses was that the role of requesting and performing a test should lie with the prescriber, although there was also frequent reference made to the fact that pharmacists should still have access to the results.
Lack of knowledge of PGx also featured heavily. In addition, the cost or resources needed to provide a PGx service was also raised directly by 19 respondents. Of these, 89.4% of the comments were related to the cost or resource implications to the pharmacy or NHS.
In addition to this feedback, respondents were asked if there was anything additional that they felt they would require to suggest amendments based on a PGx result (Question 22). By far the most common response was for PGx guidelines with 74.5% of qualifed pharmacists and 75% of in-training pharmacists highlighting this. After guidelines, an increased knowledge of genetics and PGx were cited by over 60% of respondents in both cohorts.
Financial remuneration was the least cited response with only 14.3% of the pharmacist cohort and 19.1% of the intraining cohort feeling it would be necessary to be able to ofer a service.
Over 50% of qualifed pharmacists had no ethical concerns regarding using PGx, this dropped to 39.7% for the intraining cohort, though the percentage that would not use PGx due to ethical concerns remained consistent at 1.5% in both groups.

Furthering PGx Education for Pharmacists
When asked if respondents "felt that PGX was/is an important part of their undergraduate education" (Question 32), there was a clear divide between the qualifed and intraining cohorts, with 6.3% of the qualifed cohort answering agree/strongly agree compared with 32.7% of their intraining counterparts as shown in Table 3.
Most respondents across both cohorts cited PGx as a low/medium learning priority. When the data for the learning priorities for qualifed pharmacists was broken down further (Table 4) and correlated with previous PGx education it was noted that those who had stated that PGx education was not a priority for them had a lower percentage of previous exposure comparative to those who did consider it a priority.
Finally, respondents were asked via which mediums they would like to learn more about PGx. Te most popular choice was online CPD, with over half of respondents from all cohorts selecting this option. Other media suggested included podcasts and lunchtime meetings. One respondent highlighted that PGx was not currently integrated into the curriculum of the non-medical prescriber course in the UK.

Discussion
Tis survey aimed to provide an assessment of the current understanding of PGx by UK pharmacists and pharmacy students in addition ascertaining the future educational and infrastructure needs of pharmacists to adopt PGx into practice. Te fndings of this survey indicate that there is a substantial amount of work to be carried out to prepare the UK pharmacy profession for the advent of PGx into routine clinical practice.
Some variation in PGx exposure was expected based on sector of work, years qualifed or year of study (for students) as, in the UK, the Master of Pharmacy (MPharm) degree only implemented PGx as a mandatory component of the required undergraduate curriculum in 2011. Te results of this survey demonstrate a clear generational divide in exposure to PGx education which will need rectifying prior to nationwide PGx implementation. Tese fndings mirror those of a 2013 study which utilised semistructured interviews with UK pharmacogenetics and pharmacy stakeholders and practitioners [13] and a 2020 US survey investigating the role postgraduate education and training in pharmacist's knowledge and attitudes of pharmacogenomic testing [14].   Te statistically signifcant diference in previous education levels within the qualifed pharmacist cohort itself is of particular interest. From this fnding, it can be ascertained that a variety of educational materials will need to be developed which range from introductory materials to more advanced PGx applications to accommodate the heterogeneity of previous exposure. As this study ofers quantitative data on this generational gap, it would be possible to repeat the survey following the implementation of wide-reaching post-graduate PGx education to ascertain if this has been successful reducing the diversity in PGx exposure opportunities.
When considering if PGx education correlated to confdence, the results suggest that despite over 75% of all respondents having previous education, only 15.7% of these either agreed or strongly agreed when asked about their confdence in which drugs required PGx testing. Tis fnding is not unique to the UK; a survey of pharmacists practicing in the Netherlands also identifed that while approximately half of the 727 respondents had experienced prior PGx training, only 14.1% felt adequately informed about availability and application in practice [12]. In addition, over 60% of the qualifed pharmacists did not feel confdent in identifying drugs that require PGx testing, a fnding which is similar to those identifed in a 2011 US survey of 303 pharmacists which noted that just under 75% of respondents could not identify medications which required PGx testing [11].
When it comes to facilitating PGx implementation, over 80% of respondents stated that guidelines on the use of PGx would assist them in implementing PGx based recommendations in addition to further education. Tis echoes the fndings of the survey of the US pharmacists which identifed the need for further education as a barrier to PGx implementation [14]. Financial remuneration was cited the least and this fnding is similar to those identifed within the Ubiquitous PGx European survey of healthcare professionals [10].
Whilst some international PGx guidelines exist, such as those provided by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenomics Working Group (DPWG), the utilisation of these resources by the qualifed pharmacist cohort was low. Tis fnding correlated closely to those of a survey of Canadian Pharmacists and Nurse Practitioners which identifed that only 4% of respondent had utilised CPIC and PharmGKB and only 2% had utilised DPWG [15]. Whilst utilisation was slightly higher in the in-training cohort, it is important that developed learning packages provide clear links to current guidelines either from international sources or an NHS/ National Institute for Clinical Excellence (NICE) equivalent when available.  It is also possible, however, that part of the lack of guideline utilisation refects that the majority pharmacist respondents had not yet encountered PGx in their professional practice due to limited testing availability within the NHS at present.
Most respondents across both cohorts cited PGx as a medium learning priority or lower. In part, this may be due to a lack of understanding as to where PGx may ft into their practice due to the NHS Genomic Medicine Service not being fully rolled out at the time of the survey [16]. Te results of this survey demonstrated that pharmacists for whom PGx learning was not a priority had lower exposure to previous PGx education and those who cited it as a high priority had the highest levels of previous education. Tis trend indicates that introducing PGx education early in pharmacist training may foster further learning and, for those qualifed pharmacists who had not yet encountered PGx, a brief introductory session may provide the basis for desired ongoing learning.
Presently, there is no formal training pathway for pharmacists following qualifcation with the exception of fulflment of self-directed CPD [17]. Often ongoing training varies considerably by sector with formal postgraduate clinical diplomas remaining largely within the remit of hospital pharmacy [17]. In 2014, the RPS began ofering its "Foundation Pharmacy Framework" [18] which is open to all practicing pharmacists but, as a practice based framework, in certain sectors may not allow for exposure to PGx. It is therefore important to consider where PGx training falls in the scope of ongoing training for pharmacists.
A limitation of this work is that the largest proportion of pharmacist respondents were working in the hospital sector and so may be unable to fully represent the diferences between pharmacy sectors in the UK. Due to the sample size, the study was also inadequately powered to detect statistically signifcant diferences between sectors of the profession. In addition, the "undergraduate" cohort consisted of students across all 4 years of study (and therefore, PGx exposure) but due to the small sample size of the group, these were collated for analysis. Future work looking specifcally at this group would be benefcial in understanding the nature of undergraduate PGx education over the coming years.
In addition, this survey only assessed the views of pharmacists and those training to be pharmacists. Te UK pharmacy sector consists of other pharmacy professionals including technicians and assistants all of whom may have a variety of opinions and experience with PGx which were not captured within the scope of this study. Further potential work on this topic may also include focus groups of pharmacy professionals exploring what they feel their responsibilities within UK PGx provision could include. For example, a study undertaken in the US demonstrated that over 50% of community pharmacists felt that their role should include counselling patients on PGx information [19]. Such work undertaken within the UK, with both pharmacists and other healthcare professionals, could provide a basis for the structure of PGx provision in the UK.
In conclusion, the data encapsulated within this study indicate a generational divide in PGx knowledge within the UK pharmacy profession and that most qualifed pharmacists have not yet encountered PGx within their practice. Te UK pharmacy sector is not alone in these fndings and faces much the same challenges as other parts of the world in the implementation of PGx into clinical practice. Providing introductory PGx training may increase interest in ongoing learning and that online learning was the preferred medium for PGx education. Furthermore, our fndings are important in providing a baseline understanding of the UK pharmacy workforces awareness of and skills gap in pharmacogenomics, which should help in developing appropriate undergraduate curricula and post-graduate continued learning packages. Further work needs to be undertaken to better understand intersectional diferences in PGx exposure in the UK pharmacy setting, and the opinions of other members of the pharmacy profession and the full extent of the role pharmacists expect to deliver in clinical PGx provision.

Data Availability
Te data used to support the fndings of this study are available from the corresponding author upon request.

Conflicts of Interest
Te authors declare that there are no conficts of interest.