An investigation into adverse drug reaction monitoring by United Kingdom hospital pharmacy departments

Prior to the nationwide introduction of the Committee on Safety of Medicines “yellow card” adverse drug reaction reporting for hospital pharmacists, a study was carried out to investigate the activities undertaken by hospital pharmacists in adverse drug reaction (ADR) reporting. A survey of 200 United Kingdom hospitals was conducted and 172 (86 per cent) questionnaires were returned. Local ADR reporting schemes were in operation in 26 (15.1 per cent) surveyed hospitals. The majority used locally designed cards to report ADRs. The most common reasons for the lack of a local ADR scheme (n=141) were staffing, the fact that a scheme had never been considered, time factors and the lack of perceived need to operate a scheme. Of these 141 departments, 80.1 per cent said they would consider implementing schemes in their hospital. With the inclusion of pharmacists in the CSM “yellow card” scheme, there is an incentive for them to become officially and further involved in the management and reporting of ADRs. Local ADR reporting schemes encourage pharmacovigilance and could allow pharmacists to take a leading role in this area of clinical practice.     

Restoring confidence in vaccines by explaining vaccine safety monitoring: is a targeted approach needed?

Public trust in childhood vaccines is crucial to achieving adequate immunisation coverage to ensure population-level immunity. However, in the UK, immunisation uptake has been adversely affected by vaccine safety scares, such as those surrounding whooping cough and measles, mumps and rubella (MMR). It is our belief that greater public awareness of safety surveillance schemes may play a key role in improving trust in vaccine safety. Many parents of vaccination-age children are unaware of the procedures in place for postmarketing surveillance of vaccines. Thus, we propose specific steps for generating such awareness, such as assisting parents to report suspected adverse reactions directly to the Medicines and Healthcare products Regulatory Agency (MHRA) via the Yellow Card scheme, providing information about adverse reaction reporting with vaccination information packs, and displaying posters and leaflets to convey the message that patient concerns and experiences are taken seriously by the MHRA and to generate further awareness about the scheme. In addition, healthcare staff should be encouraged to report suspected adverse reactions relating to vaccine products. Unresolved issues about the scientific usefulness of data reported by parents and the potential for these steps to increase parental concern and expectations require further investigation.     

Pharmacovigilance in China: development and challenges

Background Rational drug use and drug safety are becoming increasingly important concerns in China with the increasing public access to drugs and the health-care system, and this has led to the development of pharmacovigilance in China. Aim of the review To provide a brief introduction about pharmacovigilance in China in terms of system development, utilization and challenges. Method Relevant studies on pharmacovigilance related to the study aim was undertaken through literature search to synthesize the extracted data. Results The creation and evolvement of China’s pharmacovigilance system spans across 30 years since 1989. The system consists of four progressing administrative layers: county, municipal, provincial and national levels. China has passed over 20 laws and regulations related to pharmacovigilance covering the processes of drug development, manufacture, distribution and use with the aim to guard drug safety. An online spontaneous self-reporting Adverse Drug Reaction (ADR) Monitoring System was established in 2003. ADRs are mainly reported by medical institutions, pharmaceutical manufacturers, and drug distributors. Currently there is no mandatory ADR reporting requirement for pharmaceutical manufacturers, and a proposed regulation under public comment will likely change this. China has started to build active pharmacovigilance surveillance programs in addition to the passive ADR reporting system. The China Food and Drug Administration has established the intensive Safety Monitoring Program and the National Adverse Drug Reaction Monitoring Sentinel Alliance Program based on electronic health records to further the efforts of ADR reporting, monitoring and analysis. Conclusion The practice of ADR monitoring and pharmacovigilance in China have made great progress. More efforts are needed both in system building, and creation of laws and regulations to strengthen the safe use of medicines.     

欧盟预防用疫苗药物警戒特殊要求及启示

目的:通过对欧盟预防用疫苗药物警戒特殊要求的介绍,为完善和发展我国疫苗不良反应报告和监测体系提供借鉴和参考。方法:对欧盟药品管理局官方网站有关药物警戒以及预防用疫苗特殊要求的文献资料进行分析研究。结果与结论:欧盟预防用疫苗药物警戒工作在风险管理系统、定期安全性更新报告、上市后安全性研究、信号管理、批次召回或封存等方面值得借鉴和参考,对于我国开展疫苗药物警戒的重要意义、风险管理、病例定义标准化以及安全性沟通等方面提出了思考和启示。     

Knowledge, attitudes, and perceptions of pharmacists to adverse drug reaction reporting in Iran

Objective Adverse Drug Reactions (ADRs) are a major cause of patient morbidity and mortality. Spontaneous reporting of ADRs remains the cornerstone of pharmacovigilance and is important in maintaining patient safety. In order to determine whether our pharmacovigilance system could be improved, and identify reasons for under-reporting, a study to investigate the role of pharmacists in ADR reporting was performed in Shiraz. Setting: The pharmacies in Shiraz, capital of Fars province in Iran. Methods A questionnaire was prepared to investigate knowledge and attitude of pharmacists regarding ADR reporting. The questionnaire was given to 200 pharmacists who participated in a pharmacist association meeting. Main outcomes measured: The knowledge of pharmacovigilance practice, reasons for not reporting ADR, and perceptions of the Iranian pharmacists on pharmacovigilance practice were evaluated Results The response rate was 55% (n = 110). 29% of the respondents were not aware of the Iranian Pharmacovigilance Center. More than half of those responding felt that ADR reporting should be voluntary, while 26% felt it was a professional obligation. As for the purposes of ADR reporting scheme, 60% of the pharmacists falsely believed that monitoring ADR spontaneous reports aims at measuring the incidence of ADR. 42% of the pharmacists indicated that they have suspected an ADR without reporting it. Doubt about causality was the major reason for not reporting an ADR. Although our ADR center states that all suspected reactions to any drug on the market must be reported, only 17% of the respondents seemed to be aware of this responsibility. Conclusion Our pharmacists have little knowledge regarding the operation, purposes, and usefulness of ADR spontaneous reporting system. However, education and training will be important in maintaining and increasing ADR reports from pharmacists.     

儿童用药的药物警戒特征和模式探讨

目的论述开展儿童药物警戒工作的重要性、特征以及方法,探索儿童用药药物警戒模式。方法根据欧洲药品管理局发布的儿童用药药物警戒指南,分析儿童用药的特征。结果儿童用药不良事件潜在发生率不低于成人,而且,儿童用药的不良反应特征与成人相比有差异。结论应结合我国儿童用药不良反应监测工作现状,建立科学的儿童用药不良反应监测模式。     

Attitudes of hospital pharmacists to adverse drug reactions and the “yellow card” scheme: a qualitative study

Objective — To elicit the views of hospital pharmacists towards adverse drug reaction (ADR) reporting. Method — Qualitative, semi-structured interviews were conducted on a face to face basis using a prepiloted questionnaire. Analysis was carried out using Winmax Pro, content analysis and comparison of interpretation by two independent reviewers. Setting — All major hospitals in one Committee on Safety of Medicines/Medicines Control Agency (CSM/MCA) regional monitoring centre in England. Key findings — It was considered that introduction of reporting had been poorly publicised and promoted. Only 42 per cent of those interviewed had submitted more than one “yellow card” report and a similar percentage had reported none. The CSM/MCA has a poor image in terms of accessibility and its perceived opinion of pharmacists' role in reporting. Feedback from the CSM/MCA was satisfactory and Current Problems in Pharmacovigilance was highly regarded. Several factors appear to be dissuading pharmacists from participation in the scheme, including lack of clinical knowledge, pressure of work and a lack of time. The absence of a fee did not appear to be a deterrent to reporting; in fact, a fee was considered inappropriate. Initial schemes for education and training were perceived as having been successful. However, ongoing training needs had not been fully addressed. Conclusion — While hospitals pharmacists acknowledge ADR reporting as part of their professional role, it is not yet considered as part of their daily practice and requires more vigorous promotion. Further investigation and quantitative work are required to investigate fully this aspect of pharmacy practice.     

Different standards for reporting ADRs to herbal remedies and conventional OTC medicines: face-to-face interviews with 515 users of herbal remedies

Aims To determine whether adverse drug reactions (ADRs) to herbal remedies would be reported differently from similar ADRs to conventional over-the-counter (OTC) medicines by herbal-remedy users.
Methods Face-to-face interviews (using a structured questionnaire) with 515 users of herbal remedies were conducted in six pharmacy stores and six healthfood stores in the UK. The questionnaire focused on the likely course of action taken by herbal-remedy users after experiencing an ADR associated with a conventional OTC medicine and a herbal remedy.
Results Following a 'serious' suspected ADR, 156 respondents (30.3%) would consult their GP irrespective of whether the ADR was associated with the use of a herbal remedy or a conventional OTC medicine, whereas 221 respondents (42.9%) would not consult their GP for a serious ADR associated with either type of preparation. One hundred and thirty-four respondents (26.0%) would consult their GP for a serious ADR to a conventional OTC medicine, but not for a similar ADR to a herbal remedy, whereas four respondents (0.8%) would consult their GP for a serious ADR to a herbal remedy, but not for a similar ADR to a conventional OTC medicine. Similar differences were found in attitudes towards reporting 'minor' suspected ADRs.
Conclusions Consumers of herbal remedies would act differently with regard to reporting an ADR (serious or minor) to their GP depending on whether it was associated with a herbal remedy or a conventional OTC medicine. This has implications for herbal pharmacovigilance, particularly given the increasing use of OTC herbal remedies. The finding that a high proportion of respondents would not consult their GP or pharmacist following ADRs to conventional OTC medicines is also of concern.     

Patient versus Healthcare Professional Spontaneous Adverse Drug Reaction Reporting: A Systematic Review

Background: Increasing numbers of national pharmacovigilance schemes are accepting adverse drug reaction (ADR) reports from patients. The extent to which patient ADR reports contribute to pharmacovigilance requires comparisons to be made with reports from healthcare professionals (HCPs). Objective: This systematic review was conducted to identify all comparative studies of patient and HCP ADR reports to national pharmacovigilance schemes. Methods: We conducted a systematic review (which complied with the PRISMA statement) and a narrative synthesis of the results. Electronic databases (1996-2011) were searched, including MEDLINE, EMBASE and PHARM-Line, and supplementary searching of reference lists of included studies, authors' personal reference lists and internet searches was carried out. Studies that compared patient and HCP ADR reports submitted to national reporting schemes were considered for inclusion. Independent, duplicate data extraction, quality assessment and risk of bias were undertaken. Results: Of the 949 hits generated, three comparative studies were identified and included in this review. These studies were conducted on the national pharmacovigilance schemes in the Netherlands, Denmark and the UK. Considerable variation was observed across the national schemes in terms of the proportion of total ADR reports submitted by patients. Some of this variation may be explained by the duration that the schemes have been in operation. The number of serious ADR reports as a percentage of total reports was similar for patients compared with HCPs within each study, but varied across studies. Similarities were shown with the Netherlands and the UK in terms of drugs reported. Both studies featured statins and proton pump inhibitors in the top five drugs. Clear differences were shown between patients and HCPs in the body systems affected by ADRs as well as the therapeutic categories reported in both the UK and Danish studies. There was considerable similarity when considering the nature of ADRs reported. The Dutch study also showed similarities between patients and physicians in terms of the types of drugs for which ADRs were reported. Conclusions: Despite the large and increasing number of national pharmacovigilance schemes that accept ADR reports from patients, few comparative studies have been undertaken of patient and HCP reporting. Comparison across schemes is challenging because of differences in reporting processes, the inclusion criteria of schemes and different reporter types. The true value of patient ADR reports to pharmacovigilance will remain unknown unless more comparative evaluations are undertaken. This systematic review has highlighted both similarities and differences between reporter behaviour, the implications of which, in terms of signal generation, require further exploration.     

Reported paediatric adverse drug reactions in the UK 2000-2009

AIMS

The UK Medicines and Healthcare products Regulatory Agency (MHRA) runs a national spontaneous reporting system (Yellow Card Scheme) to collect ‘suspected’ adverse drug reaction (ADR) data. MHRA advice is to report all suspected ADRs in paediatric (<17 years) patients.

METHODS

Data on all ADRs reported to the MHRA in patients <17 years from the years 2000–9 were supplied in two datasets, inclusive and exclusive of vaccines.

RESULTS

Of 222 755 ADR reports received by the MHRA from 2000–9, 31 726 (14.2%) were in children <17 years. The number of reports in 2000 was greater than in subsequent years (12 035) due to a national vaccination programme (Meningococcal Serogroup C conjugate vaccine). The median number of ADR reports per annum (2001–2009) for children was 2146 (95% CI 1801, 2575). Vaccines were included in 22 102 (66.5%) paediatric ADR reports, with Meningococcal Serogroup C conjugate vaccine reported most frequently (12 106 reports) and headache the commonest symptom (3163). Excluding vaccines, methylphenidate (653 reports) and atomoxetine (491) were the most commonly reported medications, and the most commonly reported symptom was vomiting (374). Reporting by nurses increased from 396 in 2001 to 1295 in 2009 (41.8% of all reports); reporting by doctors stayed constant. Reports from patients, parents or carers more than doubled but remained infrequent (1.5% in 2005, 4.0% in 2009).

CONCLUSIONS

Although under-reporting is probably common, the Yellow Card Scheme in the UK receives more than 2000 reports per year on patients <17 years. Nurses now report more suspected ADRs in children than any other healthcare professional.     

Quality,efficacy and safety of complementary medicines: fashions,facts and the future. Part II: Efficacy and safety

This is the second of two papers which review issues concerning complementary medicines. The first reviewed the extent of use of complementary medicines, and issues related to the regulation and pharmaceutical quality of these products; the second considers evidence for the efficacy of several well-known complementary medicines, and discusses complementary-medicines pharmacovigilance. The term complementary medicines describes a range of pharmaceutical-type preparations, including herbal medicines, homoeopathic remedies, essential oils and dietary supplements, which mainly sit outside conventional medicine. The use of complementary medicines is a popular healthcare approach in the UK, and there are signs that the use of such products is continuing to increase. Patients and the public use complementary medicines for health maintenance, for the treatment or prevention of minor ailments, and also for serious, chronic illnesses. There is a growing body of evidence from randomized controlled trials and systematic reviews to support the efficacy of certain herbal extracts and dietary supplements in particular conditions. However, many other preparations remain untested. Strictly speaking, evidence of efficacy (and safety) for herbal medicines should be considered to be extract specific. Pharmacovigilance for complementary medicines is in its infancy. Data are lacking in several areas relevant to safety. Standard pharmacovigilance tools have additional limitations when applied to investigating safety concerns with complementary medicines.     

Factors influencing the spontaneous reporting of adverse drug reactions--the experience of the Slovak Republic

The system of adverse drug reaction (ADR) monitoring in the Slovak Republic is greatly influenced by changes taking place in the current health care delivery system. Under-reporting and reporting biases due to selective ADR reporting provide very serious problems in pharmacovigilance. In the year 2001, the number of reported ADRs increased due to reports of angiotensin converting enzyme (ACE) inhibitor-induced cough; this coincided with limits being imposed on the use of angiotensin-II receptor antagonists. These factors provide an example of selective ADR reporting, deforming the quality of drug safety monitoring. They also indicate that administrative strategies can significantly affect spontaneous reporting activities.     

Spontaneous Reporting to Regulatory Authorities of Suspected Adverse Drug Reactions to COVID-19 Vaccines Over Time: The Effect of Publicity

Drug Safety - The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published frequent summaries of spontaneous reports of suspected adverse drug reactions (ADRs) (Yellow Cards) to...     

药品不良反应信号检测方法研究

目的：探索适合我国的药品不良反应（ADR）信号检测方法。方法：检索各种ADR信号检测方法有关文献,对其进行研究、分析和比较。结果：目前各国普遍使用的信号检测方法主要有频数法和贝叶斯法,前者主要有比例报告比法、报告比值比法、MHRA法等,后者包括贝叶斯判别可信区间递进神经网络模型与相对比值法等。结论：建议我国信号检测的实施综合采用BCPNN、PRR、ROR、MHRA等多种方法。     

Evolving paradigms in pharmacovigilance

All medicines have adverse effects as well as benefits. The aim of pharmacovigilance is to protect public health by monitoring medicines to identify and evaluate issues and ensure that the overall benefits outweigh the potential risks. The tools and processes used in pharmacovigilance are continually evolving. Increasingly sophisticated tools are being designed to evaluate safety data from clinical trials to enhance the likelihood of detecting safety signals ahead of product registration. Methods include integration of safety data throughout development, meta-analytical techniques, quantitative and qualitative methods for evaluation of adverse event data and graphical tools to explore laboratory and biometric data. Electronic data capture facilitates monitoring of ongoing studies so that it is possible to promptly identify potential issues and manage patient safety. In addition, GSK employs a number of proactive methods for post-marketing signal detection and knowledge management using state-of-the-art statistical and analytical tools. Using these tools, together with safety data collected through pharmacoepidemiologic studies, literature and spontaneous reporting, potential adverse drug reactions can be better identified in marketed products. In summary, the information outlined in this paper provides a valuable benchmark for risk management and pharmacovigilance in pharmaceutical development.     

A survey on factors that could affect adverse drug reaction reporting according to hospital pharmacists in Great Britain.

INTRODUCTION: Since April 1997, UK hospital pharmacists have been invited to submit reports of suspected adverse drug reactions (ADRs) to the Committee on Safety of Medicines (CSM) and Medicines Control Agency. Three studies have investigated the involvement of hospital pharmacists in ADR reporting; however, they did not investigate the possible factors that could affect ADR reporting. OBJECTIVES: (i) To analyse the extent to which hospital pharmacists think that specified factors could affect reporting ADRs; (ii) to identify any additional factors that could hinder reporting; and (iii) to recommend possible methods to improve reporting. METHODS: Piloted questionnaires were sent to 548 hospital pharmacists in Great Britain randomly selected by the Royal Pharmaceutical Society of Great Britain (RPSGB) from their computer database. 346 questionnaires were returned and 280 were included in this study. RESULTS: 46% of the pharmacists had identified ADRs that were considered to be reportable according to the CSM criteria in the 6 months prior to the survey. 39% did not report these ADRs either to the CSM or the manufacturers. Only 8.2% reported that their hospitals had a written policy; conversely, 73.7% agreed that such a policy could enhance ADR reporting. Although not statistically significant, the result showed an increasing tendency to report ADRs by pharmacists who had received training. Furthermore, there was an increasing tendency to report ADRs with increasing seniority. DISCUSSION: The results show that hospital pharmacists say they are more likely to report serious and rare ADRs and ADRs associated with newly marketed drugs. Factors that could reduce ADR reporting included being busy at work, lack of confidence in recognising ADRs and the fear of breaching patient confidentiality. Most common suggestions on methods to improve ADR reporting were to provide ADR training and meetings (34%) and a hospital written policy (24%). RECOMMENDATIONS: ADR training and meetings would be a useful step in improving hospital pharmacist ADR reporting. Therefore, we recommend that the CSM and the RPSGB liaise with regional drug information centres and schools of pharmacy to provide more study days and training programmes for hospital pharmacists. Furthermore, the CSM should write to the 'Drugs and Therapeutics Committee' of each hospital and encourage them to develop a written local policy for pharmacist ADR reporting. Further studies should be conducted to test the recommendations noted here, assessing the response of the pharmacists in terms of absolute numbers of reports made. It would be particularly interesting to study the need for a written hospital policy and education.     

基于FAERS数据库的奥马环素不良反应信号挖掘与分析

目的 利用美国FDA不良事件报告系统（FAERS）对奥马环素进行药物不良反应（ADR）高危信号挖掘，为临床合理安全使用奥马环素提供参考。方法 下载2018年第4季度至2023年第2季度共19个季度的数据的FAERS数据，采用报告比值比法（ROR）和综合标准法（MHRA）对奥马环素的相关ADR报告数据进行信号挖掘。结果 共获取以奥马环素为首要怀疑药物的ADR报告1 180例，ROR法和MHRA法获得的奥马环素ADR风险信号基本一致，共获得奥马环素ADR信号35个，以植入物部位外渗和牙齿变色的ADR信号最强，且以胃肠道系统疾病（如恶心呕吐）最为多见，有12个ADR未在奥马环素药品说明书中出现。结论 利用FAERS数据库可对奥马环素的ADR信号进行挖掘与分析，可为临床合理安全用药提供依据。     

欧盟药物警戒额外监测制度简介与启示

2013年随着欧盟《良好药物警戒管理规范x》的生效,药品额外监测制度得到进一步完善。药品额外监测制度是一种通过建立监测目录、公开目录药品信息、采用特定标识等措施,鼓励医务人员和患者自发报告可疑不良反应,以便顺利开展上市后安全性评价,确保任何新的用药安全隐患能够被及时发现和有效避免的制度。通过介绍欧盟药物警戒额外监测制度,阐述我国药品不良反应（ADR）监测的现状,指出该制度是一种积极主动发现用药风险的尝试;学习和借鉴该制度,有助于我国弥补原有药品ADR报告系统低报、漏报等缺陷,主动开展用药安全监测,从而获得更加全面科学的结果。     

Innovations for the future of pharmacovigilance.

Post-marketing pharmacovigilance involves the review and management of safety information from many sources. Among these sources, spontaneous adverse event reporting systems are among the most challenging and resource-intensive to manage. Traditionally, efforts to monitor spontaneous adverse event reporting systems have focused on review of individual case reports. The science of pharmacovigilance could be enhanced with the availability of systems-based tools that facilitate analysis of aggregate data for purposes of signal detection, signal evaluation and knowledge management. GlaxoSmithKline (GSK) recently implemented Online Signal Management (OSM) as a data-driven framework for managing the pharmacovigilance of marketed products. This pioneering work builds upon the strong history GSK has of innovation in this area. OSM is a software application co-developed by GSK and Lincoln Technologies that integrates traditional pharmacovigilance methods with modern quantitative statistical methods and data visualisation tools. OSM enables the rapid identification of trends from the individual adverse event reports received by GSK. OSM also provides knowledge-management tools to ensure the successful tracking of emerging safety issues. GSK has developed standard procedures and 'best practices' around the use of OSM to ensure the systematic evaluation of complex safety datasets. In summary, the implementation of OSM provides new tools and efficient processes to advance the science of pharmacovigilance.