Adverse drug reaction

Purpose: The UK’s ‘Yellow Card Scheme’ for reporting of adverse drug reactions (ADRs) has been operating for 50 years, but reporting rates by community pharmacists remain low. The aim of the study was therefore to investigate the views and experiences of ADR reporting by community pharmacists in Wales, with a particular focus on the potential barriers and facilitators to reporting. Methods: Following Ethics approval and piloting, a self-complete questionnaire was mailed to all registered community pharmacies in Wales, UK (n=713). A follow-up mailing was sent to non-responders after two weeks. Results: A response rate of 52% (n=372) was achieved, of whom 57% had never submitted a yellow card. Key barriers to reporting were not seeing ADRs, difficulty identifying the causative drug, not being sure which ADRs to report and lack of time. Key facilitators were being able to report through dispensary software and having clearer guidelines about what to report. Differences between those who had previously reported ADRs and those who had not suggested lack of confidence and uncertainty about what to report were more of a barrier for non-reporters. Conversely, reporters wanted feedback on reports, ability to keep reports on their dispensary records and remuneration to aid them with reporting. Conclusions: While the respondents generally expressed positive attitudes towards ADR reporting, a number of barriers and potential facilitators were nevertheless identified. Clearer support and guidance for reporting, such as through a ‘champions’ scheme similar to that run in Welsh hospitals may help current non-reporters to engage.


Introduction
Adverse drug reactions (ADRs) are of huge significance to healthcare in terms of the burden to individuals' health and wellbeing, as well as the costs associated with treating patients with ADRs 1 .In order to identify (and ideally therefore prevent) such ADRs, pharmacovigilance systems have been set up in many countries 2 .These predominantly utilise spontaneous reports from health professionals and, increasingly, patients to monitor the safety of drugs throughout their marketed life.
It is 50 years since the 'Yellow Card Scheme' (YCS) for spontaneous reporting of ADRs was launched in the United Kingdom 3 .In the intervening years, a range of initiatives, including widening access, have been implemented to increase reporting rates, including allowing community pharmacists to join the scheme in 1999 3 .Nevertheless, in common with many other spontaneous reporting schemes, under-reporting (including by community pharmacists) is a limitation 4 .
The reasons for low reporting rates by community pharmacists are not easy to identify.Research which has looked into this issue is predominantly from countries where ADR spontaneous reporting schemes are relatively newly established such as India, Iran, Nepal, Nigeria and Saudi Arabia [5][6][7][8][9][10][11][12][13] .The authors of these studies have identified possible reasons for non-reporting of ADRs such as lack of knowledge of the reporting schemes and processes, lack of awareness of the scheme, lack of access to reporting forms, lack of certainty regarding causality, reactions which are seen are too mild to report, reactions too well known to report and workload and time pressures [5][6][7][8][9][10][11][12][13] .These findings may, however, be associated with the relative newness of the schemes -particularly lack of knowledge of how it works or access to forms.Nevertheless even in countries with more established schemes where pharmacists have been involved for longer, a number of barriers have been noted such as uncertainty regarding causation [14][15] , lack of time [14][15][16] , reactions which are seen are minor 15 , reactions which are seen are well-known 14,16 and simply forgetting to report 15 .
In the UK, published studies which investigated community pharmacists' role in ADR reporting were undertaken at the time when ADR reporting by community pharmacists was a pilot scheme (in the late 1990s) 17,18,19 .Reasons for not reporting were identified as being the fact the reaction was well recognised 17,19 , there was not enough information about the ADR 17 , they were not sure about causality 19 and there was insufficient time in the working day for reporting 17 .As considerable time has now passed and reporting by pharmacists has become established, reporting rates might be expected to have increased and indeed reporting rates by pharmacists in general have increased 20 .Nevertheless, overall reporting by community pharmacists, particularly within Wales, is still relatively low [21][22][23][24] ; for example, just 4% of reports in Wales came from community pharmacists in 2013-14 21 .Although initiatives such as linking ADR reporting to the New Medicine Service in England have boosted community pharmacist rates locally -such as a 92% increase in 2011-2 in the Northern and Yorkshire region 25 , the levels still remain lower than for hospital pharmacists and doctors.It is important therefore to find out what is preventing community pharmacists from reporting.
The aim of the study was therefore to investigate the views and experiences of ADR reporting by community pharmacists in Wales, with a particular focus on the potential barriers and facilitators to reporting.

Methods
Attitudes and experiences of community pharmacists working in Wales towards ADR reporting were assessed through means of a cross-sectional postal survey.Approval was granted from a University Ethics Committee to undertake the study.
The questionnaire was developed based on the literature and exploratory interviews with a purposive sample of seven community pharmacists covering a range of roles and levels of experience including experience of the YCS.The questions included pharmacist demographics and experience of training on ADRs and reporting through the yellow card scheme.A further section asked about barriers and facilitators to reporting, while the final section provided a number of statements with which respondents were asked to indicate their level of agreement using a 5-point Likert-style scale ranging from strongly agree to strongly disagree.Questions were predominantly closed-format, although space was provided to expand on some answers (see appended questionnaire).There was opportunity at the end of the questionnaire for respondents to add any further comments on the topic.
Following piloting on a random sample of 140 pharmacies in a demographically similar region in the North East of England, a few changes were made to the questionnaire.Most were related to formatting, but some additional questions were added relating to additional roles and qualifications and also respondents were asked to identify their main barrier / facilitator (if they had one).
The amended questionnaire was mailed to all registered community pharmacies in Wales (n=713) addressed to 'The Pharmacist'.This was for reasons of practicality and also ensured that those sent a questionnaire were actively working in community pharmacy.The addresses were obtained from the NHS Direct Wales website 26 .Each questionnaire was coded to allow identification of non-responders and to determine the region in which the pharmacy was based.The mailing pack also contained a cover letter and freepost envelope.Respondents were asked to return the completed questionnaires within two weeks.After two weeks, nonresponders were identified and a repeat mailing sent.
Data were analysed in SPSS® version 20 using descriptive statistics and comparative analysis between reporters and non-reporters through the YCS, using Fisher's exact test.Qualitative data was coded and analysed using content analysis or thematic analysis as appropriate.

Results
A total of 372 questionnaires were returned; a response rate of 52%.There were equivalent proportions of male and female pharmacists (49.5% vs 50.4%) -other key demographics are shown in Table 1.In terms of experience of ADR reporting, 57% (208/368) of respondents had never reported an ADR through the YCS.
Pharmacists were presented with a list of possible factors which may deter or prevent people from reporting ADRs.They were asked to tick all of those with which they agreed (four people did not answer this question).Respondents were then asked if they had one main barrier and, if so, to note which it was: 102 respondents stated a main barrier (one stated more than one option).The results are shown in Table 2. Non-reporters were more likely to identify lack of confidence, uncertainty over what to report and not seeing ADRs as being barriers than were those who had previously reported an ADR (p=0.001,p=0.012, p<0.0005, respectively, Fisher's exact test).
Pharmacists were then given a list of possible factors which may encourage people to report ADRs.They were asked to tick all of those with which they agreed (fifteen people did not answer this question).Respondents were then asked if they had one main facilitator and, if so, to note which it was: 120 respondents stated a main facilitator (four stated more than one option).The results are shown in Table 3. Non-reporters were more likely than reporters to identify clearer guidance as a facilitator (65% vs 52%, p=0.007Fisher's Exact) while reporters were more likely to identify getting feedback from the MHRA, being able to keep records of ADR reports in their dispensing software and remuneration as facilitators than did nonreporters (Table 3).Non-reporters were also more likely than reporters to state that nothing would encourage them to report (5% vs 1%, p=0.030).
In the final section of the questionnaire, a series of statements based on the literature or on the interviews were presented to the pharmacists who were asked to express their level of agreement with each statement.These related to a wide range of aspects of ADRs and ADR reporting.The respondents indicated positive attitudes towards reporting with the majority disagreeing with the statement that "ADR reporting is not my responsibility" (45% disagreed and 44% strongly disagreed).Similarly, the majority agreed that "I see ADR reporting as part of my professional role" (23% strongly agreed and 65% agreed).There were also positive attitudes towards patient reporting of ADRs with 11% strongly agreeing and 53% agreeing that they would be happy to encourage a patient to report through the YCS.Statements relating to identification of ADRs and reporting of ADRs are presented in Tables 4 and 5.
Although the reporters' overall view of the scheme was not significantly different from that of non-reporters, some differences were noted between reporters and non-reporters for certain statements.These differences are presented in Table 6.

Discussion
This study sought to obtain the views of community pharmacists working in Wales regarding ADR reporting.In general it was found that these pharmacists had positive views about ADR reporting, although fewer than half had ever submitted a report.Of the main barriers to reporting which were highlighted, a number were those previously identified in studies in other countries with established schemes [14][15][16] , suggesting that community pharmacists in the UK are no different in terms of these universal issues such as time pressures and difficulties in identifying causative drugs.Similarly, harder to modify factors such as not seeing reportable reactions [14][15][16] were also identified in the present study.
What was a more surprising finding in the current study was the lack of confidence in identifying and knowing how to report ADRs.This lack of certainty was also reflected in the proposed facilitators where respondents said they needed clearer guidance about what to report.While these factors have previously been reported in countries with newer reporting schemes [5][6][7][8][9][10][11][12][13] , UK community pharmacists have been involved in ADR reporting for almost 20 years.Further, during the pilot of community pharmacist ADR reporting only 3% said they lacked confidence to report 17 .Since many of these pilot pharmacists received training as part of their participation, this may account for their confidence; likewise a study in Norway 27 found that training pharmacists helped address some of these factors.Since the issues around knowledge and confidence were particularly highlighted by those respondents who had never reported an ADR it may be these individuals would most benefit from some targeted training.Although, what is not clear is the relationship between these factors -are confident pharmacists more likely to report or do they become confident because they have had the experience of reporting?Further research into this association would be beneficial.
While other research has identified barriers to reporting, there has been little consideration of what the potential reporters themselves think would increase their ability and willingness to report.The present study was able to identify a number of such facilitators which could increase reporting rates.The MHRA have already identified that many health professionals are unaware of the scheme 28 and while the respondents were generally aware of the scheme they still felt they needed more information about what they should be reporting -this could be addressed through promotional activities and alerts.Reminders and alerts appear to be beneficial in terms of acting as a prompt to increase reporting rates but the effects wear off over time 29 .Therefore if these were to be utilised, as suggested by respondents, they would need to be appropriately timed to avoid reminder-fatigue.Peer support can also be a facilitator -the 'Yellow Card Champions' initiative launched in Wales in 2013 uses local hospital pharmacist 'champions' to promote ADR reporting in their workplace and support colleagues in reporting and has been associated with a rise in hospital pharmacist reporting 21 .The scheme was extended to community-based pharmacists in 2016 30 and it is hoped that this will have a similar impact in due course.
In terms of technology, a smart-phone ADR reporting application was launched by the MHRA in 2015 31 , but this idea was not particularly popular with the study respondents as a facilitator.Rather, they preferred a system which would enable the pre-population of yellow card report forms from dispensary software.The use of such systems linkage between GP software and ADR reporting software has already resulted in significant increases in the numbers of GP reports submitted in England 20 and a similar approach could likewise enhance community pharmacist reporting, as suggested by the authors of a review paper in 2005 32 .
One facilitator which was particularly highlighted by those with experience of reporting was remuneration.This may reflect their views of the time and work involved in reporting, in contrast to those without such experience.This was also highlighted during the pilot phase of community pharmacist ADR reporting in the late 1990s, with 37% of respondents believing a fee would increase reporting rates 17 .A small number of studies have looked at the role of small financial incentives for reporting and found this did lead to an increase in report numbers 33,34 but it is not clear whether the costs are warranted for the benefits or whether the same (or greater) benefits can be achieved through other means.As such, this is unlikely to be taken up as a realistic facilitator by MHRA.
Although the response rate for this study was only 52%, this is not unusual for similar surveys of pharmacists regarding ADRs 6,8,14 .Importantly the sample included pharmacists actively working in community practice and therefore in a position to have opportunity to identify and report ADRs.A wide mix of demographics was also clear, suggesting a broad range of viewpoints could be obtained.Although a higher than expected proportion of respondents had reported an ADR, even these engaged participants were able to identify barriers and potential facilitators which may help to further enhance reporting rates.
It is clear that, despite low reporting rates, community pharmacists demonstrate positive views about the importance of ADR reporting and are not averse to submitting reports with the right support in place.It is therefore hoped that more can be done to provide this support, such as provision of further training, alerts, peer support and innovative technology approaches.Such provisions can enable these willing pharmacists to become more active reporters, with subsequent benefits for patient safety.

Adverse Drug Reaction Reporting Questionnaire
The aim of this study is to find out the views and experiences of community pharmacists, like you, with regard to adverse drug reaction (ADR) reporting and the MHRA's Yellow Card Scheme.
It doesn't matter if you have not reported an ADR: your views are really important to this research, regardless of whether or not you have made a report through the Yellow Card Scheme.
The questionnaire should take no more than 10 minutes to complete.
A freepost envelope is provided for you to return your questionnaire.
Please remember that all replies are completely confidential.

Instructions:
Please just tick one answer for each question unless instructed otherwise.
Please note that the abbreviation 'ADR' for 'adverse drug reaction' is used throughout this questionnaire.'Adverse drug reaction' is being used to cover all drug-induced effects from minor side effects to serious reactions.

A) Background Questions
In order to help analyse the data, please answer the following questions about yourself:

Table 2
Barriers to reporting (respondents could select more than one barrier then were asked to identify if they had a single main barrier)

Table 5
Statements relating to reporting of ADRs (barriers and facilitators): data presented as number of responses

Table 6
Differences in responses to statements about ADR reporting between previous reporters and previous non-reporters of ADRs (data presented as %)

tick all which apply)
How did you submit this report?Using a Yellow Card from the BNF, sent in the post Using a Yellow Card downloaded from the MHRA website, sent in the post Using a Yellow Card you obtained from elsewhere (please where below) How did you find the process of reporting?(Please tick

all which apply)
Which of these would be the main factor to encourage you? ____________________ ________________________________________ ( D) Views on ADR reportingD1a) What are the factors that deter or prevent you from reporting ADRs? (Please tick all which apply) D1b) Which of these is the main barrier for you?__________________________________ ___________________________________ (Leave blank if no single main barrier) D2) What factors would encourage you to report ADRs? (Please tick all which apply)

Leave blank if no single main factor) D3)
Which of the following do you feel have a responsibility to report ADRs? (Please

tick all which apply)
It doesn't work very well and improvements are needed If you feel improvements are needed, please use the box below to briefly explain what these are.If the Yellow Cards were more accessible If I had a way of reporting through my normal dispensary software If there was a reminder about reporting on the front of the BNF If I had a reporting app for my smartphone If there was clearer guidance about which reactions to report For EACH of the following statements, please indicate your level of agreement.Statement Do you have any other comments about ADR reporting?If so, please use the box below.

for taking the time to complete this questionnaire
Now please place it in the freepost envelope provided and return to: Pharmacy Education and Practice, FREEPOST CF3505, Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB