Spontaneous reporting of adverse drug reactions in an Italian region: Six years of analysis and observations

Pharmacovigilance started in Italy in 1965, and from 1987 reporting of ADRs has been mandatory. Doctors have to send the filled forms on suspected ADRs to the Local Health Districts which transmit biannually all the reports to the Health Department. In a Northern Italian Region (Veneto) spontaneous reporting of adverse drug reactions (ADRs) has been studied during the period 1988–1993. This Region contributes a substantial percentage of the total Italian reports. The total number of reports was 3700, most of these (54 per cent) coming from GPs. A great variability in the reporting rate among the 36 districts of Veneto Region (range: 0–8.8 per 10,000 inhabitants per year) and an important under-reporting have been evident. Underreporting is also emphasized by the fact that in 1993 the Veneto doctors who sent at least one report were only 2.7 per cent. On the whole about 35 per cent of reports concerned minor reactions caused by drugs which have a well known toxicological profile. Comparison between reports coming from Veneto and the UK in some cases show a similar safety profile (omeprazole and simvastatin), whereas in other cases (e.g. terfenadine, glafenine, fluoxetine) no correspondence can be found. This article reveals the limits of the actual spontaneous reporting in Italy and suggests some possible measures for improving it.     

The importance of direct patient reporting of suspected adverse drug reactions: a patient perspective

AIM

To explore the opinions of patient reporters to the UK Yellow Card Scheme (YCS) on the importance of the scheme.

METHODS

Postal questionnaires were distributed on our behalf to all patient reporters submitting a Yellow Card to the Medicines and Healthcare Regulatory Agency (MHRA) between March and December 2008, with one follow-up reminder to non-responders. Qualitative analysis was undertaken of responses to an open question asking why respondents felt patient reporting was important. This was followed up by telephone interviews with a purposive sample of selected respondents.

RESULTS

There were 1362 evaluable questionnaires returned from 2008 distributed (68%) and 1238 (91%) respondents provided a total of 1802 comments. Twenty-seven interviews were conducted, which supported and expanded the views expressed in the questionnaire. Four main themes emerged, indicating views that the YCS was of importance to pharmacovigilance in general, manufacturers and licensing authorities, patients and the public and health professionals. Reporters viewed the YCS as an important opportunity to describe their experiences for the benefit of others and to contribute to pharmacovigilance. The scheme''s independence from health professionals was regarded as important, in part to provide the patient perspective to manufacturers and regulators, but also because of dismissive attitudes and under-reporting by health professionals.

CONCLUSION

Direct patient reporting through the YCS is viewed as important by those who have used the scheme, in order to provide the patient experience for the benefit of pharmacovigilance, as an independent perspective from those of health professionals.     

Quality check of spontaneous adverse drug reaction reporting forms of different countries

Adverse drug reactions (ADRs) are considered as one of the leading causes of death among hospitalized patients. Thus reporting of adverse drug reactions become an important phenomenon. Spontaneous adverse drug reaction reporting form is an essential component and a major tool of the pharmacovigilance system of any country. This form is a tool to collect information of ADRs which helps in establishing the causal relationship between the suspected drug and the reaction. As different countries have different forms, our aim was to study, analyze the suspected adverse drug reaction reporting form of different countries, and assess if these forms can capture all the data regarding the adverse drug reaction. For this analysis we identified 18 points which are essential to make a good adverse drug reaction report, enabling proper causality assessment of adverse reaction to generate a safety signal. Adverse drug reaction reporting forms of 10 different countries were collected from the internet and compared for 18 points like patient information, information about dechallenge–rechallenge, adequacy of space and columns to capture necessary information required for its causality assessment, etc. Of the ADR forms that we analyzed, Malaysia was the highest scorer with 16 out of 18 points. This study reveals that there is a need to harmonize the ADR reporting forms of all the countries because there is a lot of discrepancy in data captured by the existing ADR reporting forms as the design of these forms is different for different countries. These incomplete data obtained result in inappropriate causality assessment. Copyright © 2010 John Wiley & Sons, Ltd.     

Feedback for patients reporting adverse drug reactions; satisfaction and expectations

Objective: Due to the rising number of patient reports in pharmacovigilance, the manner in which feedback is provided to patients is an element to be considered. The objective is to explore the satisfaction of patients towards personalized and general feedback in response to their reported adverse drug reactions (ADRs).

Methods: Patients who reported an ADR to the Dutch Pharmacovigilance Centre for the first time in the period between October 2012 and April 2013 were included. Reporters received personalized feedback or a general acknowledgement letter. Satisfaction towards the received feedback, expressed on a 5-point Likert scale (1 very good to 5 very poor), was studied using a web-based questionnaire. Data were analyzed using Pearson Chi-square test and linear regression analysis. Statistical significance was based on p < 0.05.

Results: A total of 471 patient-reporters were contacted with a total response of 52.5%. Respondents of both groups were satisfied with the received feedback, average score 2 (good). Respondents of the personalized feedback-group were however more satisfied score 2.0 versus 2.5 (p < 0.001) and considered the feedback more clear and useful compared with respondents of the acknowledgement letter-group, respectively score 1.6 versus 1.7 (p = 0.01) and score 2.1 versus 2.5 (p < 0.001).

Conclusion: Patients reporting ADRs are satisfied with feedback received from the pharmacovigilance centre, whether this is a personalized feedback or a general acknowledgment letter. They find it clear, useful and it meets their expectation. Although differences were found between the two types of feedback, these differences did not indicate dissatisfaction towards the received feedback.     

Attitudinal survey of voluntary reporting of adverse drug reactions

AIMS: Voluntary adverse drug reaction (ADR) reporting schemes have operated since the early sixties in many Western countries. It is generally recognized, however, that only a small proportion of ADRs is actually reported. The current survey was conducted to assess attitudes towards reporting of ADRs, and to study which types of ADRs are reported. METHODS: A questionnaire seeking reasons for nonreporting was sent to a random sample of 10% of medical practitioners in The Netherlands in October 1997. After 6 weeks, a reminder was sent to those who had not responded. RESULTS: One thousand four hundred and forty-two (73%) questionnaires were returned, of which 94% were complete. The percentage of GPs (51%) which had ever reported an ADR to the national reporting centre was significantly higher than the percentage of specialists (35%), who reported more often to the pharmaceutical industry (34% vs 48%). 86% of GPs, 72% of surgical specialists and 81% of medical specialists had ever diagnosed an ADR, which they had not reported. Uncertainty as to whether the reaction was caused by a drug (72%), the ADR being trivial (75%) or too well known (93%) were the most important reasons for not reporting. 18% were not aware of the need to report ADRs, 22% did not know how to report ADRs, 38% did not have enough time, 36% thought that reporting was too bureaucratic and only 26% of Dutch physicians knew which ADRs to report. A serious ADR, an unlabelled ADR, an ADR to a new drug, history of reporting of one or more ADRs, and specialty were all independently associated with reporting of 16 hypothetical ADRs. Surgical and medical specialists tended to report less often than GPs. CONCLUSIONS: There is a considerable degree of underreporting, which might partly be explained by lack of knowledge and misconceptions about spontaneous reporting of adverse drug reactions.     

Pharmacists' attitudes towards the reporting of suspected adverse drug reactions in Norway

BACKGROUND: In Scandinavian countries, pharmacists have not reported adverse drug reactions (ADRs), either due to legislative restrictions or because of lack of tradition. From 1 January 2005, Norwegian pharmacists have been encouraged by the Norwegian Medicines Agency to take a larger role in the reporting of ADRs. OBJECTIVE: To explore pharmacists' attitudes towards pharmacovigilance and their experiences with ADR reporting, to evaluate the effect of an educational programme and to compare these findings to the attitudes in a control group. METHODS: From September 2004, pharmacies in two of Norway's five health regions were invited to attend a 3-month ADR reporting study, and 39 pharmacies were recruited. One pharmacist from each pharmacy participated in a 1 day pre-study educational programme and a 1 day post-study evaluation meeting. Pharmacists involved in the study answered a questionnaire (A) regarding their attitudes to ADR reporting (active group). A control group answered the same questionnaire. One reminder was sent. The active group evaluated the study by answering questionnaire A once more and an evaluation questionnaire (B). Qualitative aspects of ADR reporting were discussed with the active group post-study. RESULTS: The response rate for questionnaire A was 97% (n = 158) in the active group, 74% (n = 184) in the control group and the response rate for questionnaire A and B post-study was 68% (n = 105) in the active group. Pharmacists in the active group had more positive attitudes to ADR reporting after taking part in the study than the control group (p < 0.001). Lack of time, confidence and knowledge of reporting rules could potentially prevent them from reporting ADRs. CONCLUSIONS: The pharmacists had positive attitudes towards pharmacovigilance, but very little experience with reporting. The educational programme clarified their role and increased their knowledge about the reporting requirements.     

Drugs and dilated cardiomyopathies: a case/noncase study in the French PharmacoVigilance Database

AIMS

To evaluate putative associations between drugs and dilated cardiomyopathy.

METHODS

We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were all the observations with dilated cardiomyopathy registered into the FPVD between 1 January 1990 and 30 June 2007. Noncases were all other reports other than those studied. Anthracyclines were used as positive controls. Data were expressed as reporting odds ratio (ROR) with their 95% confidence intervals.

RESULTS

Out of the 258 729 adverse drug reaction (ADR) reports recorded in the FPVD between 1 January 1990 and 30 June 2007, 47 (22 men, mean age 49 years) were defined as dilated cardiomyopathy. In these 47 patients, 67 drugs were ‘suspect’. A significant ROR was found with cytotoxic (epirubicin, mitoxantrone, cyclophosphamide, gemcitabine, fluorouracil) and antiretroviral (lamividune, zidovudine, abacavir) but also with isotretinoin, prednisone, appetite suppressant (clobenzorex) and psychotropic [antipsychotic (clozapine, olanzapine), lithium, antidepressant (clomipramine, amitriptyline, fluvoxamine)] drugs.

CONCLUSIONS

The present study describes an association between some drugs and reports of dilated cardiomyopathies. This relationship involves not only some already suspected drugs (anthracyclines, antiretrovirals), but also other drugs (antipsychotics, lithium, antidepressants, retinoids) less known to induce such an ADR. Despite the mandatory limits of this kind of study (underreporting, confounding factors …), these data represent a pharmacovigilance signal and could contribute to establish further prospective studies in order to confirm such signals.     

Using a capture-recapture method to assess the frequency of adverse drug reactions in a French university hospital

AIMS: There is evidence that different methods used to identify and quantify adverse drug reactions (ADR) in hospitals are not exhaustive (spontaneous reporting or computerized medical databases). The combination of these different sources of data could improve knowledge about ADR frequency in hospitals. The aim of this study was to estimate the incidence of serious ADRs handled in medical wards of a French university hospital using data from the Programme de Medicalization des Systemes d'Information (PMSI) and spontaneous reports recorded in the French Pharmacovigilance Database. METHODS: The study period was the first semester of 2001. RESULTS: From PMSI, all hospitalization summaries including an ICD-10th code related to a potential ADR were selected. From the French Pharmacovigilance Database, all serious ADRs which occurred during the study period and were reported by physicians working in the University Hospital were collected. After identification of common cases, the capture-recapture method was applied in order to estimate the real number of ADRs occurring during the first semester of 2001. From PMSI, we identified 274 different hospital stays related to an ADR. Out of 241 reports selected from the French Pharmacovigilance Database, we retained 151 ADRs for analysis. Fifty-two ADRs were common in the two databases, giving an estimated number of serious ADRs of 796 [95% confidence interval (CI) 638, 954], corresponding to 2.9% of inpatients (95% CI 2.3, 3.5). CONCLUSIONS: This study shows the lack of exhaustiveness of ADR reporting whatever the sources of data and underlines the interest of merging data from different databases to identify fully the real impact of ADR in hospitals.     

Spontaneously reported fatal suspected adverse drug reactions: a 10-year survey from Sweden

PURPOSE: One of the main methods for monitoring the safety of marketed drugs is spontaneously reporting of suspected adverse drug reactions (ADRs). The objective of this study was to describe the pattern of spontaneously reported fatal adverse drug reactions (FADRs) by analysing data from the national spontaneous reporting system in Sweden. METHODS: In Sweden it is compulsory to report all new or serious suspected ADRs to the Medical Products Agency. The information in these reports is stored in the national database SWEDIS (Swedish Drug Information System). All suspected FADRs reported to SWEDIS between 1 January 1995 and 31 December 2004 were reviewed and analysed. RESULTS: During the study period 990 reports of FADRs were found. The main distribution of suspected FADRs was: haemorrhages (n = 603; 60.9%), blood and bone marrow dysfunction (n = 71; 7.2%), sudden death (n = 38; 3.8%) and pulmonary embolism (n = 30; 3.0%). Antithrombotic agents were the drugs most frequently implicated in the FADRs (n = 605; 61.1%). Vitamin K antagonists were reported in 453 cases (45.8%) and acetylsalicylic acid in 82 cases (8.3%). Among the fatalities with blood and bone marrow dysfunction methotrexate was the most frequently reported drug. For sudden death and pulmonary embolism, antipsychotics and oestrogen containing drugs, respectively, were most commonly reported. CONCLUSIONS: Bleeding complications amounted more than half of all reports of FADRs and vitamin K antagonists were implicated in most of these reports. However, as spontaneous reporting systems are primarily set up for signalling purposes, the data must be interpreted with utmost care.     

Patient reporting of suspected adverse drug reactions: a review of published literature and international experience

AIMS: To synthesize data from published studies and international experience to identify evidence of potential benefits and drawbacks of direct patient reporting of suspected adverse drug reactions (ADRs) by patients. METHODS: Structured search of MEDLINE, CINAHL and PsycINFO supplemented by internet searches and requests for information to key contacts. RESULTS: Seven studies (eight papers) were included in the review. None of the studies concerned spontaneous reporting by patients. Information on patient reporting systems was obtained for six countries, with summary data reported by four. Patient reports identified possible new ADRs that had not previously been reported by health professionals. The quality of patient reports appears to be similar to that of health professional reports. There is some evidence that patients report an ADR when they consider their health professional has not paid attention to their concerns. Patient reports may, at least initially, be more time consuming to process. CONCLUSIONS: Overall, the evidence indicates that patient reporting of suspected ADRs has more potential benefits than drawbacks. Evaluation of patient reporting systems is needed to provide further evidence.     

Incretin-mimetics associated pancreatitis: evidence from the spontaneous adverse drug reactions reporting in Italy

Objective: New incretin-mimetics increased the treatment options for type 2 diabetes mellitus. Studies on the safety of incretin-based therapy showed a risk of hypersensitivity reactions, acute pancreatitis, renal failure, infection, thyroid and pancreas cancer. We contributed to safety assessment of these new drugs by evaluating the spontaneous adverse drug reactions (ADRs) reporting in Italy.

Research and methods: Reports of suspected ADRs associated with incretin-mimetics were selected from the Italian Spontaneous ADR Reporting Database. For a subgroup of cases belonging to the Hospital of Cento (Ferrara), levels of pancreatic enzymes, amylase and lipase, before and after the therapy with the incretin-mimetics were available.

Results: As of December 2012, the reports of ADR associated with hypoglycemic drugs (excluding insulin) were 2443, 1169 (47.85%) concerned the incretin-mimetics. A total of 90 reports described pancreatitis (44) and elevated pancreatic enzymes (46). Out of 90 cases, 34 were serious (37%). Data on amylase/lipase values for 10 patients were provided and an analysis of the published literature was performed.

Conclusions: Our data from the daily clinical practice add up and confirm the information available on the association between incretin-mimetics and pancreatic damage and suggest caution in the prescribing of these new drugs and a close monitoring of exposed patients.     

Adverse drug reactions in children: a ten-year review of reporting to the Portuguese Pharmacovigilance System

Objective: Adverse drug reactions (ADR) are a public health problem. They cause significant morbidity, mortality and health costs. Less is known about pediatric ADR. Our goal was to characterize a pediatric case series of ADR reported to the Portuguese Pharmacovigilance System (PPS) during the past 10 years.

Research design and methods: Retrospective analysis of ADR reports concerning patients till 17 years old received by the PPS between 2003 and 2012. We evaluated patients’ demographic data and involved drugs, as well as characteristics and seriousness of reactions, stratified by age groups.

Results: We found 1742 reports (50% females) corresponding to 9.7% of the total received. The age of the patients varied from 0 to 17 years (median: 5 years, interquartile range: 10.6), with 566 cases (32%) occurring in patients younger than 2y. Among the 1195 serious cases, 31% (370) episodes led to hospitalization. In 32 cases (2%) there was a fatal outcome. Most of the ADR reported referred to general disorders and administration site conditions, followed by skin and subcutaneous tissue reactions. Vaccines were the most represented group (42%) followed by antibacterials for systemic use (17%).

Conclusions: Pediatric ADR represents about 10% of the reports received by the PPS. Most ADR were considered serious. Major findings varied according to age groups.     

Adverse drug reactions in Ghanaian children: review of reports from 2000 to 2012 in VigiBase

Objective: The aim of this article is to describe adverse drug reactions (ADRs) reported for children aged 0 – 17 years in Ghana.

Methods: Paediatric reports submitted by the Ghana National Centre for Pharmacovigilance to the World Health Organisation (WHO) Global ADR database, VigiBase up to December 2012 were extracted. The data were analysed for number of reports per year, types of reporters and suspected ADRs and drugs.

Results: A total of 343 reports for children were received during the period. The drug classes most frequently reported were vaccines (115, 31%), antimalarials (106, 28%) and antibiotics (57, 15%). Of the top 20 individual drugs, 19 were anti-infectives. The most frequently reported ADRs were injection site infection, fever and rash. There were 23 deaths reported, and antimalarials were implicated in 12 cases.

Conclusions: Vaccines, antimalarials and antibiotics are the leading medicines reported to cause ADRs in Ghanaian children. There was a high mortality rate, with many of the deaths due to causes explained in the individual case safety reports.