Expert Opinion on Drug Safety
ISSN: 1474-0338 (Print) 1744-764X (Online) Journal homepage: http://www.tandfonline.com/loi/ieds20
Improvement of patient adverse drug reaction reporting through a community pharmacist-based intervention in the Campania region of Italy Elisabetta Parretta, Concetta Rafaniello, Lara Magro, Anna Coggiola Pittoni, Liberata Sportiello, Carmen Ferrajolo, Annamaria Mascolo, Maurizio Sessa, Francesco Rossi & Annalisa Capuano To cite this article: Elisabetta Parretta, Concetta Rafaniello, Lara Magro, Anna Coggiola Pittoni, Liberata Sportiello, Carmen Ferrajolo, Annamaria Mascolo, Maurizio Sessa, Francesco Rossi & Annalisa Capuano (2014) Improvement of patient adverse drug reaction reporting through a community pharmacist-based intervention in the Campania region of Italy, Expert Opinion on Drug Safety, 13:sup1, 21-29 To link to this article: http://dx.doi.org/10.1517/14740338.2014.939582
Published online: 29 Aug 2014.
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Date: 21 September 2015, At: 12:53
Original Research
1.
Introduction
2.
Methods
3.
Results
4.
Discussion
5.
Conclusion
Improvement of patient adverse drug reaction reporting through a community pharmacist-based intervention in the Campania region of Italy Elisabetta Parretta†, Concetta Rafaniello, Lara Magro, Anna Coggiola Pittoni, Liberata Sportiello, Carmen Ferrajolo, Annamaria Mascolo, Maurizio Sessa, Francesco Rossi & Annalisa Capuano
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†
Second University of Naples, Campania Regional Center for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Faculty of Medicine and Surgery, Naples, Italy
Objective: Adverse drug reaction (ADR) reporting by patients has a fundamental role in pharmacovigilance. The main objectives of the present study were to assess the impact of a pharmacist-based intervention in promoting direct patient reporting, to evaluate patient ability to identify and report ADRs and to determine their pattern. Research design and methods: The study involved 96 pharmacists in the Campania region of Italy, who interviewed their customers and asked them whether they had experienced an ADR. Patients who had experienced an ADR were invited to complete an ADR reporting form. The quality of completed ADR reporting forms was evaluated before their entry into the Italian Spontaneous Reporting System (Rete Nazionale di Farmacovigilanza [RNF]) and, once entered, their pattern was determined. Results: A total of 18,677 patients were interviewed, and 10.88% had experienced an ADR. After quality control, 54.32% of all reporting forms were entered into the RNF so that patient contribution to spontaneous reporting, null over the years, reached ~7%. Patients reported mainly non-serious (91.28%) and expected (94.62%) ADRs, and NSAIDs or antibiotics were the most frequently reported drugs. Conclusions: The study shows that pharmacists can have an important role in promoting patient reporting and adds new information on how a patient reporting form should be structured. Keywords: direct patient reporting, pharmacist, pharmacovigilance, spontaneous reporting Expert Opin. Drug Saf. (2014) 13(Suppl.1):S21-S29
1.
Introduction
The direct reporting of adverse drug reactions (ADRs) by patients has been an increasingly important topic in the world of pharmacovigilance. The main reasons for supporting the development of patient reporting as an important component of drug safety include both the promotion of patients’ rights and equity, and the acknowledgment of the benefit that health-care organizations can provide from patient involvement [1]. In particular, since it is the patient who assumes the risks and the costs of experiencing an ADR, he/she should have the fundamental right to express oneself and be listened to. Besides their
10.1517/14740338.2014.939582 © 2014 Informa UK, Ltd. ISSN 1474-0338, e-ISSN 1744-764X All rights reserved: reproduction in whole or in part not permitted
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rights, patients may provide different information compared to health-care professionals, including suspected ADRs to over-the-counter medicines and different presentation of reactions, as well as a broader picture of ADRs and their impact on their life [2]. Although current evidence supports all these potential benefits, concerns about direct patient reporting have been expressed in terms of quality of their reports and, most importantly, that the increasing number of patient reports might create additional noise that could distract from signal detection and result in a system overload [3]. However, until now, no published evidence suggests a negative impact of patient reporting on signal detection, which is the primary aim of national spontaneous reporting systems. On the contrary, benefits of it have been demonstrated in the context of some European countries, such as the UK, Denmark and Netherlands [4-6]. The role of patients in pharmacovigilance has been recently discussed by the European Medicines Agency (EMA), and the importance of direct patient reporting has been emphasized in the new European legislation on pharmacovigilance (Regulation EU No 1235/2010 and Directive 2010/84/ EU), which has been effective in Italy since 2012 [7]. Given the proven benefits of patient reporting and the new objectives recommended by the European legislation, national regulatory agencies are now undertaking major commitments that include how to promote spontaneous reporting among patients, which methods of ADR reporting to adopt for patients and how to handle data from patient reporting. In Italy, direct patient reporting was formally introduced in April 1991, revived in 2004 and in 2010 a new electronic form was introduced [8]; patients can now download the ADR reporting form from the website of the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The completed form is mailed to the local health district pharmacovigilance center for its evaluation and entry into the Italian Pharmacovigilance Adverse Event Spontaneous Reporting System (Rete Nazionale Farmacovigilanza [RNF]) [9]. However, until 2009, RNF received only a few patient reports (206). In 2010, the Veneto region performed a study based on the involvement of community pharmacists for promoting ADR reporting by patients. In a 4-month period, RNF collected 1,794 patient ADR reporting forms [10]. As a consequence of the high number of patient ADR reporting forms derived from the Veneto study, AIFA proposed to conduct a similar study at a national level. Here, we report the results obtained in the Campania region by applying the same method used for the Veneto region study. The main objectives of our investigation were to assess the impact of a community pharmacist-based intervention in promoting direct patient reporting of ADRs, to evaluate the patient’s ability to identify ADRs, to evaluate the patient’s ability to report ADRs using the ADR reporting form currently available in Italy and to determine their pattern. S22
2.
Methods
Study design The study recruited pharmacists across the Campania region (Italy) working in community pharmacies open to the public. Each participating pharmacist was asked to interview three to four people per day over a 3-month period from November 2012 to January 2013. Patients were selected for the interview if they were ‡ 18 years and had received at least one drug in the month before the interview day. At the time of the interview, pharmacists recorded on an ad hoc monitoring form, the sex and age of the individual, and whether he/ she had experienced an adverse event potentially related to the drug treatment received in the previous month. Patients who had experienced an ADR received a reporting form to complete from the pharmacist. They could complete the ADR reporting form either on their own or with the help of the pharmacist. They could also use an electronic form available on the study website. The completed ADR reporting forms could be given back to the pharmacist or sent by fax or mail. All the ADR reporting forms were collected for evaluation by the Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology before entry into the RNF. Since the study was based on stimulated spontaneous ADR reporting, Ethical Committee approval was not required. 2.1
Patient ADR reporting form An ADR reporting form, exactly the same as the patient electronic form introduced in 2010 by AIFA, was used for the purpose of this study [9]. The ADR reporting form includes the following sections ‘information on the person who had the suspected ADR’ (age, sex, weight, height and stage of pregnancy, if applicable); ‘information on the suspected ADR’ (ADR description, date of onset, whether the ADR derives from errors in drug administration, degree of seriousness, outcome and impact on quality of life); ‘information on the drug which might have caused the ADR’ (name of the drug, whether or not the drug was prescribed, date of treatment, dose and therapeutic indication, whether the treatment had been stopped because of the ADR onset, whether the patient has been experienced the same ADR in the past and concomitant drugs); ‘information on the general practitioner’ (whether or not the general practitioner has been informed about the ADR onset, his or her name and contact details); ‘other relevant medical information’ (such as underlying medical conditions); ‘information on the reporter’ (contact details and signature). 2.2
Patient ADR reporting form evaluation ADR reporting forms were evaluated for completeness and quality of information reported. According to AIFA criteria, at the time of the start of the study, an ADR reporting form 2.3
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Patients interviewed n = 18,677
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Patients with ADRs n = 2,033
Patients without ADRs n = 16,644
ADR forms sent n = 718
ADR forms not sent n = 1,315
ADR forms entered into RNF n = 390
ADR forms excluded n = 328
Figure 1. Study development flow chart. ADRs: Adverse drug reactions; RNF: Rete Nazionale di Farmacovigilanza.
(whether deriving from a health-care professional or a patient) could be entered into RNF when the following fields were fulfilled: description of at least one ADR, inclusion of at least one suspected drug, patient initials, age and sex, date of onset of the ADR, date and dose of the suspected drug treatment and details on the reporter. After quality control, those reports that fulfilled AIFA criteria were entered into RNF. Data analysis All pharmacist monitoring forms were analyzed to calculate the number of patients interviewed, the number of those who had experienced an adverse event potentially related to a drug treatment and their distribution by age and sex. All ADR reports entered into RNF were analyzed in terms of degree of seriousness and notoriety. Regarding the first one, each patient could define the experienced ADR as ‘non-serious’ or if it resulted in a ‘life-threatening experience,’ ‘hospitalization,’ ‘persistent disability,’ ‘birth defect’ or ‘death.’ According to the EMA guidelines on good pharmacovigilance practice, those ADRs that resulted in one of the above-mentioned conditions were defined as ‘serious’ [11]. With regard to notoriety, an ADR was defined as unexpected when its nature, severity or outcome was not consistent with the summary of product characteristics [11]. 2.4
3.
Results
Study development and general description of patient data
3.1
The study involved 96 pharmacists working in community pharmacies open to the public and distributed across the region. As shown in Figure 1, from November 2012 to January 2013, a total of 18,677 patients were interviewed, with an average of 3 customers/day for each pharmacist involved in the study. Of all interviewed patients, 10.88% referred a suspected ADR to the pharmacist; however, only 35.32% of them completed the ADR reporting form and gave it back to the pharmacist. No patients sent the ADR reporting form by mail or fax or used the electronic form. According to the study protocol, all ADR reporting forms were sent to the Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology for quality control before RNF entry. Of all reporting forms, 54.32% were entered into RNF. As shown in Table 1, a higher percentage of women were interviewed, experienced an ADR, filled in the ADR form, and were reported in the ADR forms entered into RNF. As required by the study protocol, only individuals ‡ 18 years could be interviewed. The majority of patients who experienced an ADR and completed the reporting form were aged between 18 and 64 years. However, a small number of ADR reporting
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Table 1. Patients distribution by sex and age group. Patients interviewed
ADR forms sent
‡
ADR forms entered into RNF n (%){
§,{
n (%)*
n (%)
10,115 (54.16) 8562 (45.84)
1201 (59.08) 832 (40.92)
467 (65.04) 245 (34.12)
259 (66.41) 131 (33.59)
14,195 (76.00) 4480 (23.99) 18,677 (100)
1479 (72.75) 553 (27.20) 2033 (100)
515 (71.72) 183 (25.49) 718 (100)
287 (73.59) 90 (23.08) 390 (100)
n (%)
*Age was not available in two interviewed patients. z Age was not available in one ADR experienced patient. § Sex and age were not reported in six and seven ADR forms sent, respectively. { In 13 reports, the ADR was experienced by patients < 18 years. ADR: Adverse drug reaction; RNF: Rete Nazionale di Farmacovigilanza.
Reason for ADR reporting form exclusion
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Sex Women Men Age 18 -- 64 years ‡ 65 years Total
Patients with ADRs
75.00%
Date of ADR onset Suspected drug treatment period
72.26% 30.49%
Reporter details Suspected drug treatment dose Event following herbal remedies or dietary supplements Age
3.66% 2.13%
Inconsistent data Sex Supected drug ADR description
1.83% 1.83% 1.52% 1.22%
15.24%
0
50
100
150
200
250
300
Number of ADR reporting forms
Figure 2. ADR reporting forms not entered into RNF. The figure shows the number and percentage of ADR reporting forms distributed by reason of their exclusion. ADR: Adverse drug reaction; RNF: Rete Nazionale di Farmacovigilanza.
forms entered into RNF (13) regarded patients < 18 years (data not shown) as the reporter could also describe an ADR experienced by someone else (such as his/her child). Patient ADR reporting form evaluation As show in Figure 1, about 50% of all ADR reporting forms collected in the study were entered into RNF, as they fulfilled all the basic criteria required by AIFA. The main reasons for the exclusion of forms were lack of the date of the ADR onset (75.00%), lack of suspected drug treatment period or dose (72.26 and 15.24%, respectively) and lack of reporter details (30.49%) (Figure 2). Only a few reports did not report age or sex of the person experiencing an ADR, the ADR experienced, or the suspected drug. Moreover, a small number of reports recorded inconsistent data (1.83%). Finally, reports related to herbal remedies or dietary supplies (3.66%) were not entered into RNF, since the RNF only collects reports for registered drugs. The Italian National 3.2
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Institute of Health provides for the safety monitoring of adverse reactions to natural health products through a different reporting system [12]. As shown in Figure 2, the sum of reports rejected for different reasons is higher than the total number of reports, because some reports failed across multiple categories. Impact of the study on patient ADR reporting in the Campania region
3.3
The RNF database was set up in 2001, and patients can report suspected ADRs by using an ADR reporting form that is different to the one that is available for health-care professionals [13]. In 2003, the Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology was established and joined the Italian spontaneous reporting network. As shown in Figure 3, the total number of ADR reporting forms entered into RNF by the Campania Region was relatively constant in the initial years, whereas it increased dramatically from
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4000
ADR reporting form number
3500
Total numbers of ADR reporting forms Total numbers of patient ADR reporting forms
3000 2500 2000 1500 1000 500 0
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2001 2002
2003
2004 2005
2006 2007 Year
2008
2009 2010
2011 2012
2013
Figure 3. Annual number of ADR reporting forms collected by the Campania region. The figure shows the annual number of ADR reporting forms derived from the Campania region between 2001 and 2013. ADR: Adverse drug reaction.
Table 2. Distribution of ADR reporting forms by notoriety and seriousness. n (%) Notoriety Expected Unexpected Seriousness Not reported non-serious Serious Serious ADR type* Hospitalization and prolonged hospitalization Life-threatening conditions Persistent disability Other clinically relevant conditions Death
369 (94.62) 21 (5.38) 3 (0.77) 356 (91.28) 31 (7.95) 25 (80.65) 1 (3.23) 2 (6.45) 3 (9.68) 0 (0.00)
*Percentages refer to the total number of serious ADR reporting forms. ADR: Adverse drug reaction.
2007 to 2013. This increase was due to the promotion of several active pharmacovigilance and observational studies [14-24]. However, until this pharmacist-based intervention, patient contribution from the Campania region was almost null (from 2001 to 2011, RNF received only seven ADR reporting forms from patients). Apart from 18 reports, all patient reporting forms collected by RNF between 2012 and 2013 were generated due to this study. In particular, patients’ contribution to all ADR reports was 7.45% in 2012 and 7.31% in 2013. Pattern of patient ADR reporting forms As shown in Table 2, patients mainly reported expected (94.62%) and non-serious ADRs (91.28%). Among the serious ADRs, the majority were related to hospitalization 3.4
and prolonged hospitalization (80.65%). Patients mainly reported suspected ADRs related to gastrointestinal disorders (40.26%), skin and subcutaneous tissue disorders (31.54%), general and nervous system disorders (14.62 and 14.36%, respectively) (Figure 4). Finally, the most frequently reported drugs were antibiotics and NSAIDs (Table 3). 4.
Discussion
Underreporting remains a major limitation of every national spontaneous reporting system; to overcome this issue, several interventions have been developed and evaluated [25]. Until now, the main interventions can be classified as follows: educational activities to inform or teach professionals about the reporting procedure and its importance (such as oral presentations and workshops); modification of the reporting form to simplify the procedure (such as promotion of electronic forms over paper versions); assistance or help from another professional (such as a pharmacist, physician or nurse) at the time of patient reporting and implementation of a feedback to the reporter. In a recent systematic review, aimed to assess the effectiveness of different strategies to increase ADR reporting, Gonzalez-Gonzalez et al. found that target populations were health-care professionals in all 43 included papers and physicians were the target in about 80% of them [26]. The few existing studies that include patients’ ADR perspective in their intervention comprise only interviews conducted by pharmacists, nurses or physicians. Although in these studies patients were asked whether they had experienced an ADR, the ADR reporting form was always completed by a health-care professional [27,28]. The paucity of published data on the impact of interventions that encourage direct patient reporting is probably because
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E. Parretta et al.
40.26%
Gastrointestinal disorders Skin and subcutaneous tissue disorders General disorders and administration site conditions Nervous system disorders Respiratory, thoracic and mediastinal disorders Vascular disorders Psychiatric disorders Ear and labyrinth disorders Musculoskeletal and connective tissue disorders Cardiac disorders Reproductive system and breast disorders Immune system disorders Eye disorders Infections and infestations Investigations Renal and urinary disorders Metabolism and nutrition disorders Injury, poisoning and procedural complications Blood and lymphatic system disorders
31.54% 14.62% 14.36% 8.21% 5.38% 4.36% 3.59% 3.59% 3.33% 3.08% 2.56% 2.05% 1.54% 1.54% 1.03% 1.03% 0.26% 0.26%
0
20
40
60
80
100
120
140
160
180
Number of ADR reporting forms
Figure 4. Distribution of ADR reporting forms by System Organ Class (SOC). The figure shows the number and percentage of patient ADR reporting forms distributed by SOC. ADR: Adverse drug reaction.
Table 3. Suspected drugs reported with a frequency higher than 1%. Drug
n (%)
Amoxicillin/Clavulanic acid Ketoprofen Clarithromycin Amoxicillin Ciprofloxacin Acetylsalicylic acid Ceftriaxone Levofloxacin Ibuprofen Nimesulide Acetaminophen Ampicillin Cefaclor Diclofenac Azithromycin Bacterial lysate Prednisone Sulfamethoxazole/Trimethoprim Folic acid Amlodipine Enalapril Drospirenone/Ethinylestradiol Lansoprazole
41 (10.51) 20 (5.13) 18 (4.61) 15 (3.85) 15 (3.85) 11 (2.82) 10 (2.56) 10 (2.56) 9 (2.31) 9 (2.31) 8 (2.05) 6 (1.54) 6 (1.54) 6 (1.54) 5 (1.28) 5 (1.28) 5 (1.28) 5 (1.28) 4 (1.03) 4 (1.03) 4 (1.03) 4 (1.03) 4 (1.03)
patient reporting has only recently been introduced in the majority of national spontaneous reporting systems. In the United States, patients have been able to report ADRs directly since the 1960s, whereas in Europe the introduction date of direct patient reporting ranges between 1997 and 2010 [29]. In 2010, Leone et al. performed an active pharmacovigilance study to promote direct patient reporting through a S26
community pharmacist-based intervention in the Veneto region (Italy). As a result, 1,794 patient ADR reports were entered into RNF; these patient reports increased the spontaneous reporting rate in the Veneto region in 2010, compared with 2009, from 268 to 549 reports per million inhabitants (+122%) [10]. In 2012, AIFA performed that study at a national level; the Campania region took part in this larger study between November 2012 and January 2013. Main findings This study shows that the impact of our pharmacist-based intervention was relevant, as patients’ contribution to spontaneous reporting in our region, null over the years, reached ~7% during the study period. After quality control, about half of all ADR reporting forms were entered into RNF. By analyzing the content of all ADR reporting forms, new information on how they should be structured in order to guarantee higher quality data collection has been provided. Moreover, the pattern of patient reports entered into RNF with respect to the type of ADR (degree of seriousness, notoriety and system organ class) and to the suspected drug reported has been described. Patients reported mainly non-serious and expected ADRs and over-the-counter drugs, such as NSAIDs or antibiotics, were the drugs most frequently reported. 4.1
Impact of community pharmacist-based intervention on patient ADR reporting
4.2
As shown in Figure 3, during the study period (2012 -- 2013), patient reports comprised 7.45 and 7.31% of the total number of reports received by the Campania region, respectively.
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These data confirm findings from literature, which estimate that patient reports make up between 7 and 15% of total reports in those countries where patient reporting has been implemented [4]. Moreover, the data confirm those obtained by Leone et al. in terms of the impact of this intervention on patient reporting and strongly suggest that promotion of ADR reporting by community pharmacists represents a valid tool for an effective dissemination of information to patients about their role in pharmacovigilance. Patient’s ability to identify and report ADRs This study was the first one to analyze the ability of patients to correctly fill in an ADR reporting form and described the main reasons for their exclusion from a spontaneous reporting database. This aspect is an important topic for European regulatory agencies who are now trying to develop easy ways for direct patient reporting and structure a reporting form containing adequate quality of data for analysis. Indeed, the two major characteristics that a well-designed standardized reporting form should have include a patient-friendly lay language and the ability to collect key information for data analysis [30]. We believe that our data can provide important information about this issue. In Italy, patients can spontaneously report an ADR either electronically or via paper reporting (both methods are available on the website of AIFA together with explanatory text on how to report an ADR). In both cases, ADR reports are usually revised and entered into RNF by the corresponding local pharmacovigilance office. In this study, patients used an ADR format identical to the electronic one available on the AIFA website. Although pharmacists solicited ADR reporting, the reporter was the patient himself or herself, and the pharmacist only offered assistance if it was required. A total of 54.32% of all reports derived from the study were accepted as valid reports when evaluated based on AIFA minimum data requirements for their entry into RNF. Major reasons for ADR report exclusion were the lack of the ADR onset date and the suspected treatment period, followed by the lack of information on the reporter. The ADR reporting form used in this study does not underline which fields are mandatory for its entry into RNF; on the contrary, in other countries such as UK and Spain, the reporting form clearly indicates which information is mandatory [31,32]. We believe that information on the minimum data elements necessary for the analysis of ADR reports should be shared with patients in order to ameliorate their quality. More concerning is that in 30.49% of all rejected reports, the patient did not record his name and contact information. These data suggest that communication and educational interventions for promoting patient ADR reporting should also include data privacy aspects.
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4.3
Pattern of patient ADR reporting forms Analysis of patient characteristics showed that female patients completed a greater proportion of ADR reporting forms. These data are in accordance with other studies in which a 4.4
higher proportion of ADR reports related to women have been observed, irrespective of the report type, in the case of both health-care professional- and patient-derived reports. According to some authors, the higher percentage of ADRs in female patients could be due to sex-specific risk factors or female polypharmacy [33-35]. Of all suspected ADRs collected in the study, the majority were expected and reported NSAIDs or antibiotics as the suspected drug. According to some authors, patients can provide information on over-thecounter drugs and alternative or complementary medications, about which the doctor is unfamiliar. On the other hand, because they lack medical knowledge, patients can report associations that may seem unlikely from a medical point of view and give rise to new signals [36]. With regard to the degree of seriousness, only few reports referred to serious ADRs (7.95%) and, in particular, most of them were related to hospitalization (80.65% of all serious ADR reports). As described in the ICH-E2A guideline, a serious adverse event corresponds to any untoward medical occurence that results in death is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or results in a congenital anomaly/birth defect. Moreover, those medical events that require interventions for preventing the above-mentioned ADR consequences should also be considered serious [11]. In our opinion, hospitalization, disability, death and congenital anomaly or birth defects can be clearly identified by patients, whereas they can interpret life-threatening ADRs or clinically relevant conditions in a different way. This could probably explain why the majority of serious ADRs derived from our study belong to the hospitalization type, which is a more objective criteria. We believe that patients’ ability to fully understand all degrees of seriousness is an important topic of discussion and that differences in interpretation of ADR reporting forms between health-care professionals and patients should be reduced. Finally, in reference to the drugs reported as supected, those widely used in the community setting and over-the-counter medicines were the most commonly reported by patients. Furthermore, 12 reports regarding adverse events following the use of herbal remedies or dietary supplements were sent, although the study did not require it. As in the case of ADR reporting, consumer involvement in monitoring of herbal product safety is valued positively; indeed, according to the WHO, consumer reports should be accepted as a valid source of information. Although only 1.67% of the ADR reporting forms described an adverse event following herbal products or dietary supplies, our data suggest that community pharmacists could be an important asset in herbal product monitoring strategies. Strengths and limitations Our study is the first one that analyzed the ability of patients in reporting ADRs using the ADR reporting form available in Italy and focused on the main reasons for their exclusion from 4.5
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our national spontaneous reporting database. On the basis of our data, we provided new information on how a patient ADR reporting form should be structured. Our study has some limitations. First, our data refer to one Italian region and not to a national level. Second, patients could fill in the ADR reporting form with the help of the pharmacist, who in turn may have influenced the reporting form content and/or quality. Third, the study population comprised only patients who accepted to be interviewed, which is a selected population.
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Conclusion
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Acknowledgment E Parretta and C Rafaniello contributed equally to this work.
Given the proven role of patient reporting in post-marketing surveillance, each national pharmacovigilance system has to promote and facilitate ADR reporting from both health-care professionals and patients. Only few published studies describe which interventions should be taken in order to promote direct patient reporting, and none of them deals with how to ensure an easy way to report ADRs and guarantee an adequate quality of patient reports. Our study shows that community pharmacists may have an important role in pharmacovigilance not only as reporters but also in terms of patient reporting improvement. Moreover, our work indicates how a patient ADR reporting form could be potentially improved in order to guarantee high quality of the collected
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data. Finally, this intervention underlines that important issues on direct patient reporting remain open. We strongly believe that in light of the new European pharmacovigilance legislation, patient reporting experiences should be shared among different countries in order to better understand how to promote it, harmonize national patient reporting schemes and maximize the value derived from patient reporting.
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Declaration of interest This paper is part of a themed issue funded by the authors’ institution, the Second University of Naples and received additional funding from the Campania Region through the Italian Medicines Agency-AIFA. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
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Affiliation
Elisabetta Parretta†1, Concetta Rafaniello1, Lara Magro2, Anna Coggiola Pittoni2, Liberata Sportiello1, Carmen Ferrajolo1, Annamaria Mascolo1, Maurizio Sessa1, Francesco Rossi1 & Annalisa Capuano1 † Author for correspondence 1 Second University of Naples, Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Faculty of Medicine and Surgery, Via De Crecchio, 7, 80138 Naples, Italy Tel: +39 0815667652; Fax: +39 0815667652; E-mail: [email protected] 2 University of Verona, Department of Public Health and Community Medicine, Section of Pharmacology, p.le L.A. Scuro 10, 37134 Verona, Italy
Yellow card report. Medicines and Healthcare products Regulatory Agency.
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ISSN: 1474-0338 (Print) 1744-764X (Online) Journal homepage: http://www.tandfonline.com/loi/ieds20
Improvement of patient adverse drug reaction reporting through a community pharmacist-based intervention in the Campania region of Italy Elisabetta Parretta, Concetta Rafaniello, Lara Magro, Anna Coggiola Pittoni, Liberata Sportiello, Carmen Ferrajolo, Annamaria Mascolo, Maurizio Sessa, Francesco Rossi & Annalisa Capuano To cite this article: Elisabetta Parretta, Concetta Rafaniello, Lara Magro, Anna Coggiola Pittoni, Liberata Sportiello, Carmen Ferrajolo, Annamaria Mascolo, Maurizio Sessa, Francesco Rossi & Annalisa Capuano (2014) Improvement of patient adverse drug reaction reporting through a community pharmacist-based intervention in the Campania region of Italy, Expert Opinion on Drug Safety, 13:sup1, 21-29 To link to this article: http://dx.doi.org/10.1517/14740338.2014.939582
Published online: 29 Aug 2014.
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Date: 21 September 2015, At: 12:53
Original Research
1.
Introduction
2.
Methods
3.
Results
4.
Discussion
5.
Conclusion
Improvement of patient adverse drug reaction reporting through a community pharmacist-based intervention in the Campania region of Italy Elisabetta Parretta†, Concetta Rafaniello, Lara Magro, Anna Coggiola Pittoni, Liberata Sportiello, Carmen Ferrajolo, Annamaria Mascolo, Maurizio Sessa, Francesco Rossi & Annalisa Capuano
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†
Second University of Naples, Campania Regional Center for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Faculty of Medicine and Surgery, Naples, Italy
Objective: Adverse drug reaction (ADR) reporting by patients has a fundamental role in pharmacovigilance. The main objectives of the present study were to assess the impact of a pharmacist-based intervention in promoting direct patient reporting, to evaluate patient ability to identify and report ADRs and to determine their pattern. Research design and methods: The study involved 96 pharmacists in the Campania region of Italy, who interviewed their customers and asked them whether they had experienced an ADR. Patients who had experienced an ADR were invited to complete an ADR reporting form. The quality of completed ADR reporting forms was evaluated before their entry into the Italian Spontaneous Reporting System (Rete Nazionale di Farmacovigilanza [RNF]) and, once entered, their pattern was determined. Results: A total of 18,677 patients were interviewed, and 10.88% had experienced an ADR. After quality control, 54.32% of all reporting forms were entered into the RNF so that patient contribution to spontaneous reporting, null over the years, reached ~7%. Patients reported mainly non-serious (91.28%) and expected (94.62%) ADRs, and NSAIDs or antibiotics were the most frequently reported drugs. Conclusions: The study shows that pharmacists can have an important role in promoting patient reporting and adds new information on how a patient reporting form should be structured. Keywords: direct patient reporting, pharmacist, pharmacovigilance, spontaneous reporting Expert Opin. Drug Saf. (2014) 13(Suppl.1):S21-S29
1.
Introduction
The direct reporting of adverse drug reactions (ADRs) by patients has been an increasingly important topic in the world of pharmacovigilance. The main reasons for supporting the development of patient reporting as an important component of drug safety include both the promotion of patients’ rights and equity, and the acknowledgment of the benefit that health-care organizations can provide from patient involvement [1]. In particular, since it is the patient who assumes the risks and the costs of experiencing an ADR, he/she should have the fundamental right to express oneself and be listened to. Besides their
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rights, patients may provide different information compared to health-care professionals, including suspected ADRs to over-the-counter medicines and different presentation of reactions, as well as a broader picture of ADRs and their impact on their life [2]. Although current evidence supports all these potential benefits, concerns about direct patient reporting have been expressed in terms of quality of their reports and, most importantly, that the increasing number of patient reports might create additional noise that could distract from signal detection and result in a system overload [3]. However, until now, no published evidence suggests a negative impact of patient reporting on signal detection, which is the primary aim of national spontaneous reporting systems. On the contrary, benefits of it have been demonstrated in the context of some European countries, such as the UK, Denmark and Netherlands [4-6]. The role of patients in pharmacovigilance has been recently discussed by the European Medicines Agency (EMA), and the importance of direct patient reporting has been emphasized in the new European legislation on pharmacovigilance (Regulation EU No 1235/2010 and Directive 2010/84/ EU), which has been effective in Italy since 2012 [7]. Given the proven benefits of patient reporting and the new objectives recommended by the European legislation, national regulatory agencies are now undertaking major commitments that include how to promote spontaneous reporting among patients, which methods of ADR reporting to adopt for patients and how to handle data from patient reporting. In Italy, direct patient reporting was formally introduced in April 1991, revived in 2004 and in 2010 a new electronic form was introduced [8]; patients can now download the ADR reporting form from the website of the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The completed form is mailed to the local health district pharmacovigilance center for its evaluation and entry into the Italian Pharmacovigilance Adverse Event Spontaneous Reporting System (Rete Nazionale Farmacovigilanza [RNF]) [9]. However, until 2009, RNF received only a few patient reports (206). In 2010, the Veneto region performed a study based on the involvement of community pharmacists for promoting ADR reporting by patients. In a 4-month period, RNF collected 1,794 patient ADR reporting forms [10]. As a consequence of the high number of patient ADR reporting forms derived from the Veneto study, AIFA proposed to conduct a similar study at a national level. Here, we report the results obtained in the Campania region by applying the same method used for the Veneto region study. The main objectives of our investigation were to assess the impact of a community pharmacist-based intervention in promoting direct patient reporting of ADRs, to evaluate the patient’s ability to identify ADRs, to evaluate the patient’s ability to report ADRs using the ADR reporting form currently available in Italy and to determine their pattern. S22
2.
Methods
Study design The study recruited pharmacists across the Campania region (Italy) working in community pharmacies open to the public. Each participating pharmacist was asked to interview three to four people per day over a 3-month period from November 2012 to January 2013. Patients were selected for the interview if they were ‡ 18 years and had received at least one drug in the month before the interview day. At the time of the interview, pharmacists recorded on an ad hoc monitoring form, the sex and age of the individual, and whether he/ she had experienced an adverse event potentially related to the drug treatment received in the previous month. Patients who had experienced an ADR received a reporting form to complete from the pharmacist. They could complete the ADR reporting form either on their own or with the help of the pharmacist. They could also use an electronic form available on the study website. The completed ADR reporting forms could be given back to the pharmacist or sent by fax or mail. All the ADR reporting forms were collected for evaluation by the Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology before entry into the RNF. Since the study was based on stimulated spontaneous ADR reporting, Ethical Committee approval was not required. 2.1
Patient ADR reporting form An ADR reporting form, exactly the same as the patient electronic form introduced in 2010 by AIFA, was used for the purpose of this study [9]. The ADR reporting form includes the following sections ‘information on the person who had the suspected ADR’ (age, sex, weight, height and stage of pregnancy, if applicable); ‘information on the suspected ADR’ (ADR description, date of onset, whether the ADR derives from errors in drug administration, degree of seriousness, outcome and impact on quality of life); ‘information on the drug which might have caused the ADR’ (name of the drug, whether or not the drug was prescribed, date of treatment, dose and therapeutic indication, whether the treatment had been stopped because of the ADR onset, whether the patient has been experienced the same ADR in the past and concomitant drugs); ‘information on the general practitioner’ (whether or not the general practitioner has been informed about the ADR onset, his or her name and contact details); ‘other relevant medical information’ (such as underlying medical conditions); ‘information on the reporter’ (contact details and signature). 2.2
Patient ADR reporting form evaluation ADR reporting forms were evaluated for completeness and quality of information reported. According to AIFA criteria, at the time of the start of the study, an ADR reporting form 2.3
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Patients interviewed n = 18,677
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Patients with ADRs n = 2,033
Patients without ADRs n = 16,644
ADR forms sent n = 718
ADR forms not sent n = 1,315
ADR forms entered into RNF n = 390
ADR forms excluded n = 328
Figure 1. Study development flow chart. ADRs: Adverse drug reactions; RNF: Rete Nazionale di Farmacovigilanza.
(whether deriving from a health-care professional or a patient) could be entered into RNF when the following fields were fulfilled: description of at least one ADR, inclusion of at least one suspected drug, patient initials, age and sex, date of onset of the ADR, date and dose of the suspected drug treatment and details on the reporter. After quality control, those reports that fulfilled AIFA criteria were entered into RNF. Data analysis All pharmacist monitoring forms were analyzed to calculate the number of patients interviewed, the number of those who had experienced an adverse event potentially related to a drug treatment and their distribution by age and sex. All ADR reports entered into RNF were analyzed in terms of degree of seriousness and notoriety. Regarding the first one, each patient could define the experienced ADR as ‘non-serious’ or if it resulted in a ‘life-threatening experience,’ ‘hospitalization,’ ‘persistent disability,’ ‘birth defect’ or ‘death.’ According to the EMA guidelines on good pharmacovigilance practice, those ADRs that resulted in one of the above-mentioned conditions were defined as ‘serious’ [11]. With regard to notoriety, an ADR was defined as unexpected when its nature, severity or outcome was not consistent with the summary of product characteristics [11]. 2.4
3.
Results
Study development and general description of patient data
3.1
The study involved 96 pharmacists working in community pharmacies open to the public and distributed across the region. As shown in Figure 1, from November 2012 to January 2013, a total of 18,677 patients were interviewed, with an average of 3 customers/day for each pharmacist involved in the study. Of all interviewed patients, 10.88% referred a suspected ADR to the pharmacist; however, only 35.32% of them completed the ADR reporting form and gave it back to the pharmacist. No patients sent the ADR reporting form by mail or fax or used the electronic form. According to the study protocol, all ADR reporting forms were sent to the Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology for quality control before RNF entry. Of all reporting forms, 54.32% were entered into RNF. As shown in Table 1, a higher percentage of women were interviewed, experienced an ADR, filled in the ADR form, and were reported in the ADR forms entered into RNF. As required by the study protocol, only individuals ‡ 18 years could be interviewed. The majority of patients who experienced an ADR and completed the reporting form were aged between 18 and 64 years. However, a small number of ADR reporting
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Table 1. Patients distribution by sex and age group. Patients interviewed
ADR forms sent
‡
ADR forms entered into RNF n (%){
§,{
n (%)*
n (%)
10,115 (54.16) 8562 (45.84)
1201 (59.08) 832 (40.92)
467 (65.04) 245 (34.12)
259 (66.41) 131 (33.59)
14,195 (76.00) 4480 (23.99) 18,677 (100)
1479 (72.75) 553 (27.20) 2033 (100)
515 (71.72) 183 (25.49) 718 (100)
287 (73.59) 90 (23.08) 390 (100)
n (%)
*Age was not available in two interviewed patients. z Age was not available in one ADR experienced patient. § Sex and age were not reported in six and seven ADR forms sent, respectively. { In 13 reports, the ADR was experienced by patients < 18 years. ADR: Adverse drug reaction; RNF: Rete Nazionale di Farmacovigilanza.
Reason for ADR reporting form exclusion
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Sex Women Men Age 18 -- 64 years ‡ 65 years Total
Patients with ADRs
75.00%
Date of ADR onset Suspected drug treatment period
72.26% 30.49%
Reporter details Suspected drug treatment dose Event following herbal remedies or dietary supplements Age
3.66% 2.13%
Inconsistent data Sex Supected drug ADR description
1.83% 1.83% 1.52% 1.22%
15.24%
0
50
100
150
200
250
300
Number of ADR reporting forms
Figure 2. ADR reporting forms not entered into RNF. The figure shows the number and percentage of ADR reporting forms distributed by reason of their exclusion. ADR: Adverse drug reaction; RNF: Rete Nazionale di Farmacovigilanza.
forms entered into RNF (13) regarded patients < 18 years (data not shown) as the reporter could also describe an ADR experienced by someone else (such as his/her child). Patient ADR reporting form evaluation As show in Figure 1, about 50% of all ADR reporting forms collected in the study were entered into RNF, as they fulfilled all the basic criteria required by AIFA. The main reasons for the exclusion of forms were lack of the date of the ADR onset (75.00%), lack of suspected drug treatment period or dose (72.26 and 15.24%, respectively) and lack of reporter details (30.49%) (Figure 2). Only a few reports did not report age or sex of the person experiencing an ADR, the ADR experienced, or the suspected drug. Moreover, a small number of reports recorded inconsistent data (1.83%). Finally, reports related to herbal remedies or dietary supplies (3.66%) were not entered into RNF, since the RNF only collects reports for registered drugs. The Italian National 3.2
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Institute of Health provides for the safety monitoring of adverse reactions to natural health products through a different reporting system [12]. As shown in Figure 2, the sum of reports rejected for different reasons is higher than the total number of reports, because some reports failed across multiple categories. Impact of the study on patient ADR reporting in the Campania region
3.3
The RNF database was set up in 2001, and patients can report suspected ADRs by using an ADR reporting form that is different to the one that is available for health-care professionals [13]. In 2003, the Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology was established and joined the Italian spontaneous reporting network. As shown in Figure 3, the total number of ADR reporting forms entered into RNF by the Campania Region was relatively constant in the initial years, whereas it increased dramatically from
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4000
ADR reporting form number
3500
Total numbers of ADR reporting forms Total numbers of patient ADR reporting forms
3000 2500 2000 1500 1000 500 0
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2001 2002
2003
2004 2005
2006 2007 Year
2008
2009 2010
2011 2012
2013
Figure 3. Annual number of ADR reporting forms collected by the Campania region. The figure shows the annual number of ADR reporting forms derived from the Campania region between 2001 and 2013. ADR: Adverse drug reaction.
Table 2. Distribution of ADR reporting forms by notoriety and seriousness. n (%) Notoriety Expected Unexpected Seriousness Not reported non-serious Serious Serious ADR type* Hospitalization and prolonged hospitalization Life-threatening conditions Persistent disability Other clinically relevant conditions Death
369 (94.62) 21 (5.38) 3 (0.77) 356 (91.28) 31 (7.95) 25 (80.65) 1 (3.23) 2 (6.45) 3 (9.68) 0 (0.00)
*Percentages refer to the total number of serious ADR reporting forms. ADR: Adverse drug reaction.
2007 to 2013. This increase was due to the promotion of several active pharmacovigilance and observational studies [14-24]. However, until this pharmacist-based intervention, patient contribution from the Campania region was almost null (from 2001 to 2011, RNF received only seven ADR reporting forms from patients). Apart from 18 reports, all patient reporting forms collected by RNF between 2012 and 2013 were generated due to this study. In particular, patients’ contribution to all ADR reports was 7.45% in 2012 and 7.31% in 2013. Pattern of patient ADR reporting forms As shown in Table 2, patients mainly reported expected (94.62%) and non-serious ADRs (91.28%). Among the serious ADRs, the majority were related to hospitalization 3.4
and prolonged hospitalization (80.65%). Patients mainly reported suspected ADRs related to gastrointestinal disorders (40.26%), skin and subcutaneous tissue disorders (31.54%), general and nervous system disorders (14.62 and 14.36%, respectively) (Figure 4). Finally, the most frequently reported drugs were antibiotics and NSAIDs (Table 3). 4.
Discussion
Underreporting remains a major limitation of every national spontaneous reporting system; to overcome this issue, several interventions have been developed and evaluated [25]. Until now, the main interventions can be classified as follows: educational activities to inform or teach professionals about the reporting procedure and its importance (such as oral presentations and workshops); modification of the reporting form to simplify the procedure (such as promotion of electronic forms over paper versions); assistance or help from another professional (such as a pharmacist, physician or nurse) at the time of patient reporting and implementation of a feedback to the reporter. In a recent systematic review, aimed to assess the effectiveness of different strategies to increase ADR reporting, Gonzalez-Gonzalez et al. found that target populations were health-care professionals in all 43 included papers and physicians were the target in about 80% of them [26]. The few existing studies that include patients’ ADR perspective in their intervention comprise only interviews conducted by pharmacists, nurses or physicians. Although in these studies patients were asked whether they had experienced an ADR, the ADR reporting form was always completed by a health-care professional [27,28]. The paucity of published data on the impact of interventions that encourage direct patient reporting is probably because
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40.26%
Gastrointestinal disorders Skin and subcutaneous tissue disorders General disorders and administration site conditions Nervous system disorders Respiratory, thoracic and mediastinal disorders Vascular disorders Psychiatric disorders Ear and labyrinth disorders Musculoskeletal and connective tissue disorders Cardiac disorders Reproductive system and breast disorders Immune system disorders Eye disorders Infections and infestations Investigations Renal and urinary disorders Metabolism and nutrition disorders Injury, poisoning and procedural complications Blood and lymphatic system disorders
31.54% 14.62% 14.36% 8.21% 5.38% 4.36% 3.59% 3.59% 3.33% 3.08% 2.56% 2.05% 1.54% 1.54% 1.03% 1.03% 0.26% 0.26%
0
20
40
60
80
100
120
140
160
180
Number of ADR reporting forms
Figure 4. Distribution of ADR reporting forms by System Organ Class (SOC). The figure shows the number and percentage of patient ADR reporting forms distributed by SOC. ADR: Adverse drug reaction.
Table 3. Suspected drugs reported with a frequency higher than 1%. Drug
n (%)
Amoxicillin/Clavulanic acid Ketoprofen Clarithromycin Amoxicillin Ciprofloxacin Acetylsalicylic acid Ceftriaxone Levofloxacin Ibuprofen Nimesulide Acetaminophen Ampicillin Cefaclor Diclofenac Azithromycin Bacterial lysate Prednisone Sulfamethoxazole/Trimethoprim Folic acid Amlodipine Enalapril Drospirenone/Ethinylestradiol Lansoprazole
41 (10.51) 20 (5.13) 18 (4.61) 15 (3.85) 15 (3.85) 11 (2.82) 10 (2.56) 10 (2.56) 9 (2.31) 9 (2.31) 8 (2.05) 6 (1.54) 6 (1.54) 6 (1.54) 5 (1.28) 5 (1.28) 5 (1.28) 5 (1.28) 4 (1.03) 4 (1.03) 4 (1.03) 4 (1.03) 4 (1.03)
patient reporting has only recently been introduced in the majority of national spontaneous reporting systems. In the United States, patients have been able to report ADRs directly since the 1960s, whereas in Europe the introduction date of direct patient reporting ranges between 1997 and 2010 [29]. In 2010, Leone et al. performed an active pharmacovigilance study to promote direct patient reporting through a S26
community pharmacist-based intervention in the Veneto region (Italy). As a result, 1,794 patient ADR reports were entered into RNF; these patient reports increased the spontaneous reporting rate in the Veneto region in 2010, compared with 2009, from 268 to 549 reports per million inhabitants (+122%) [10]. In 2012, AIFA performed that study at a national level; the Campania region took part in this larger study between November 2012 and January 2013. Main findings This study shows that the impact of our pharmacist-based intervention was relevant, as patients’ contribution to spontaneous reporting in our region, null over the years, reached ~7% during the study period. After quality control, about half of all ADR reporting forms were entered into RNF. By analyzing the content of all ADR reporting forms, new information on how they should be structured in order to guarantee higher quality data collection has been provided. Moreover, the pattern of patient reports entered into RNF with respect to the type of ADR (degree of seriousness, notoriety and system organ class) and to the suspected drug reported has been described. Patients reported mainly non-serious and expected ADRs and over-the-counter drugs, such as NSAIDs or antibiotics, were the drugs most frequently reported. 4.1
Impact of community pharmacist-based intervention on patient ADR reporting
4.2
As shown in Figure 3, during the study period (2012 -- 2013), patient reports comprised 7.45 and 7.31% of the total number of reports received by the Campania region, respectively.
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These data confirm findings from literature, which estimate that patient reports make up between 7 and 15% of total reports in those countries where patient reporting has been implemented [4]. Moreover, the data confirm those obtained by Leone et al. in terms of the impact of this intervention on patient reporting and strongly suggest that promotion of ADR reporting by community pharmacists represents a valid tool for an effective dissemination of information to patients about their role in pharmacovigilance. Patient’s ability to identify and report ADRs This study was the first one to analyze the ability of patients to correctly fill in an ADR reporting form and described the main reasons for their exclusion from a spontaneous reporting database. This aspect is an important topic for European regulatory agencies who are now trying to develop easy ways for direct patient reporting and structure a reporting form containing adequate quality of data for analysis. Indeed, the two major characteristics that a well-designed standardized reporting form should have include a patient-friendly lay language and the ability to collect key information for data analysis [30]. We believe that our data can provide important information about this issue. In Italy, patients can spontaneously report an ADR either electronically or via paper reporting (both methods are available on the website of AIFA together with explanatory text on how to report an ADR). In both cases, ADR reports are usually revised and entered into RNF by the corresponding local pharmacovigilance office. In this study, patients used an ADR format identical to the electronic one available on the AIFA website. Although pharmacists solicited ADR reporting, the reporter was the patient himself or herself, and the pharmacist only offered assistance if it was required. A total of 54.32% of all reports derived from the study were accepted as valid reports when evaluated based on AIFA minimum data requirements for their entry into RNF. Major reasons for ADR report exclusion were the lack of the ADR onset date and the suspected treatment period, followed by the lack of information on the reporter. The ADR reporting form used in this study does not underline which fields are mandatory for its entry into RNF; on the contrary, in other countries such as UK and Spain, the reporting form clearly indicates which information is mandatory [31,32]. We believe that information on the minimum data elements necessary for the analysis of ADR reports should be shared with patients in order to ameliorate their quality. More concerning is that in 30.49% of all rejected reports, the patient did not record his name and contact information. These data suggest that communication and educational interventions for promoting patient ADR reporting should also include data privacy aspects.
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4.3
Pattern of patient ADR reporting forms Analysis of patient characteristics showed that female patients completed a greater proportion of ADR reporting forms. These data are in accordance with other studies in which a 4.4
higher proportion of ADR reports related to women have been observed, irrespective of the report type, in the case of both health-care professional- and patient-derived reports. According to some authors, the higher percentage of ADRs in female patients could be due to sex-specific risk factors or female polypharmacy [33-35]. Of all suspected ADRs collected in the study, the majority were expected and reported NSAIDs or antibiotics as the suspected drug. According to some authors, patients can provide information on over-thecounter drugs and alternative or complementary medications, about which the doctor is unfamiliar. On the other hand, because they lack medical knowledge, patients can report associations that may seem unlikely from a medical point of view and give rise to new signals [36]. With regard to the degree of seriousness, only few reports referred to serious ADRs (7.95%) and, in particular, most of them were related to hospitalization (80.65% of all serious ADR reports). As described in the ICH-E2A guideline, a serious adverse event corresponds to any untoward medical occurence that results in death is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or results in a congenital anomaly/birth defect. Moreover, those medical events that require interventions for preventing the above-mentioned ADR consequences should also be considered serious [11]. In our opinion, hospitalization, disability, death and congenital anomaly or birth defects can be clearly identified by patients, whereas they can interpret life-threatening ADRs or clinically relevant conditions in a different way. This could probably explain why the majority of serious ADRs derived from our study belong to the hospitalization type, which is a more objective criteria. We believe that patients’ ability to fully understand all degrees of seriousness is an important topic of discussion and that differences in interpretation of ADR reporting forms between health-care professionals and patients should be reduced. Finally, in reference to the drugs reported as supected, those widely used in the community setting and over-the-counter medicines were the most commonly reported by patients. Furthermore, 12 reports regarding adverse events following the use of herbal remedies or dietary supplements were sent, although the study did not require it. As in the case of ADR reporting, consumer involvement in monitoring of herbal product safety is valued positively; indeed, according to the WHO, consumer reports should be accepted as a valid source of information. Although only 1.67% of the ADR reporting forms described an adverse event following herbal products or dietary supplies, our data suggest that community pharmacists could be an important asset in herbal product monitoring strategies. Strengths and limitations Our study is the first one that analyzed the ability of patients in reporting ADRs using the ADR reporting form available in Italy and focused on the main reasons for their exclusion from 4.5
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our national spontaneous reporting database. On the basis of our data, we provided new information on how a patient ADR reporting form should be structured. Our study has some limitations. First, our data refer to one Italian region and not to a national level. Second, patients could fill in the ADR reporting form with the help of the pharmacist, who in turn may have influenced the reporting form content and/or quality. Third, the study population comprised only patients who accepted to be interviewed, which is a selected population.
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5.
Conclusion
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Acknowledgment E Parretta and C Rafaniello contributed equally to this work.
Given the proven role of patient reporting in post-marketing surveillance, each national pharmacovigilance system has to promote and facilitate ADR reporting from both health-care professionals and patients. Only few published studies describe which interventions should be taken in order to promote direct patient reporting, and none of them deals with how to ensure an easy way to report ADRs and guarantee an adequate quality of patient reports. Our study shows that community pharmacists may have an important role in pharmacovigilance not only as reporters but also in terms of patient reporting improvement. Moreover, our work indicates how a patient ADR reporting form could be potentially improved in order to guarantee high quality of the collected
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Declaration of interest This paper is part of a themed issue funded by the authors’ institution, the Second University of Naples and received additional funding from the Campania Region through the Italian Medicines Agency-AIFA. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
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Affiliation
Elisabetta Parretta†1, Concetta Rafaniello1, Lara Magro2, Anna Coggiola Pittoni2, Liberata Sportiello1, Carmen Ferrajolo1, Annamaria Mascolo1, Maurizio Sessa1, Francesco Rossi1 & Annalisa Capuano1 † Author for correspondence 1 Second University of Naples, Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Faculty of Medicine and Surgery, Via De Crecchio, 7, 80138 Naples, Italy Tel: +39 0815667652; Fax: +39 0815667652; E-mail: [email protected] 2 University of Verona, Department of Public Health and Community Medicine, Section of Pharmacology, p.le L.A. Scuro 10, 37134 Verona, Italy
Yellow card report. Medicines and Healthcare products Regulatory Agency.
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