Communication in pharmacovigilance

Pharmacovigilance is a field where communication is paramount. Information, such as single case reports, is transferred from health professionals to National Regulatory Administrations and between administrations and industry. The cumulation of reports may be used for information purposes, and to assist in the identification of possible signals. These are then assessed by the analysis of individual and aggregate cases, the latter being exchanged between administrations for multinational analysis at the European level. Once a decision has been made on a possible alert, the decisions and the reasons thereof must be transmitted to administrations and to other correspondents, such as health professionals, the pharmaceutical industry and WHO. Within the CARE project of the DGXIII European Nervous System telematics research programme, the Pharmacovigilance Pilot, consisting of representatives of the French, Spanish, and UK pharmacovigilance systems, set out to identify and describe the messages corresponding to these communication needs, and the methods best suited to effective telematic transmission. The messages identified concern: the transmission of individual case reports, the transmission of cumulative and aggregate case reports, and of regulatory decisions. Each of these information messages have been structured for future inclusion into a network for electronic data interchange between administrations in pharmacovigilance. In time they should provide a common electronic vocabulary enabling all parties involved in pharmacovigilance to communicate telematically. Transmission options have been considered also. In view of the large number of existing and potential partners involved in the communication processes in pharmacovigilance, EDI (electronic data interchange) seems the most appropriate method to exchange these messages. Two of these, concerning the single case and the aggregate cases (rapid alerts) have been submitted to the Western European EDIFACT Board MD9 for integration into EDIFACT (as MEDADR and MEDPHV).     

The single case format: Proposal for a structured message for the telematic transmission of information on individual case reports in pharmacovigilance

The development of telematic exchange of information in pharmacovigilance has as a consequence the necessary development of the messages used to transmit the information. The first of these messages is the one used to transmit information on individual case reports. Common formats exist on paper, but these have not been applied to electronic transmission. A structured message for the transmission of single case information has been developed within the ENS European research programme, by three National Pharmacovigilance administrations, and reviewed by the relevant European bodies. It has been submitted to the Western European Edifact Board MD9 for admission as an EDIFACT message, so that it will be possible to exchange information concerning these single cases, using standard EDI methodology.     

国际药物警戒体系对乍得的启示

目的为乍得药物不良反应监测体系的构建做初步的探究。方法主要通过描述性研究手段,分析乍得药品使用现状,并以国际药物警戒系统为参考,找出自身不足,明确本次研究重点。结果目前乍得药物不良反应监测体系尚不完善。结论应设置药物不良反应监测的管理机构和专业技术机构,通过立法来确保药物不良反应监测体系和不良反应救助制度的有效运作,搞好宣传工作,积极培养相关专业人才。     

Measuring the impact of the 2012 European pharmacovigilance legislation on additional risk minimization measures

Aims: Additional risk minimization measures (aRMMs) may be needed to ensure that the benefits continue to outweigh the risks for medicines associated with serious risks. Prior research showed an increasing trend in medicines with aRMMs. We assessed whether the European pharmacovigilance legislation may have impacted the number and type of aRMMs.

Methods: We included new active substances approved between 1 January 2010 and 31 December 2015. Information extracted from the summary of the Risk Management Plan at the time of licensing included date and type of marketing authorization, presence and type of aRMMs. We tested for differences using Pearson’s Χ² test and segmented Poisson regression.

Results: We identified 231 medicines approved during the study period, of which 30% had aRMMs at the time of licensing. ARMMs were in place for 38% of medicines before July 2012 and for 28% after (p = 0.16). Segmented Poisson regression did not show changes in trend or level of medicines with aRMMs.

Discussion and conclusion: During the study period, no significant differences in the proportion or trend of products with aRMMs at the time of licensing before and after the pharmacovigilance legislation were identified.     

Effect of educational intervention on healthcare providers knowledge and perception towards pharmacovigilance: A tertiary teaching hospital experience

Objective

Based on the theory on planned behavior, perception or attitude is found to be a well-established predictor of healthcare providers’ intentions to perform different behaviors. Also, improving knowledge was proposed to affect their practice as well. In Jordan, many studies have been conducted to evaluate healthcare providers’ knowledge and perception towards pharmacovigilance but no intervention or training was provided. Thus, the aim of this study was to evaluate the impact of an educational workshop on the knowledge and perception of healthcare providers towards pharmacovigilance in a Jordanian tertiary teaching hospital.

A model for the future conduct of pharmacovigilance

A scientific model to support excellence in pharmacovigilance has been developed from first principles by brainstorming sessions and discussions with experts in the field. The model represents a long-term vision of how pharmacovigilance could be conducted in the future. So far it has been developed without any consideration of constraints such as resources or the need for legislative change. Although the vision is holistic, it would be possible to test and implement parts of the model in a piecemeal fashion.     

Issues with regulatory pharmacovigilance in East European countries: the industry perspective

The new European Union pharmaceutical legislation emphasizes the importance of ensuring the continued safety of medicinal products in use with the main purpose to protect the public health. To fulfil this task the Member States are obliged to establish pharmacovigilance systems, which could be continually adapted to take account of scientific and technical progress. The non-EU East European countries are oriented towards the same goal on their way to the community. They are changing their legal frameworks for pharmacovigilance to harmonize it with the European requirements. As the EU accession country, Croatia is also in a phase of harmonization of the national legislation on medicines with the latest European requirements. It has established the pharmacovigilance system in which the Croatian Agency for Medicines and Medical Devices has very important role, and it involves all stakeholders-pharmaceutical industry, Healthcare Professionals and patient organizations. Belupo Inc. is faced with changes in the field of pharmacovigilance on all its markets: in Croatia, in EU as well as in the East European countries outside the EU, which are traditionally Belupo's target markets. The structure and functioning of the pharmacovigilance system in Croatia and other non-EU East European countries based on Belupo's experience gathered through the activities of its Pharmacovigilance Department and activities of its Qualified Persons for Pharmacovigilance (QP) are presented.     

Investigation of the characteristics of medication errors and adverse drug reactions using pharmacovigilance data in China

The aim of this study was to investigate the characteristics of medication errors (MEs) and adverse drug reactions (ADRs) using data from the spontaneous reporting system, which is helpful to understand the actual situation of MEs in China. Data from 2015 in a south distinct in Shanghai were gathered from the spontaneous reporting system and analyzed. The general information, cause of errors, severity, primary diseases, involved system and organs, symptoms, and suspected drugs were investigated. A total of 1290 adverse drug events (ADEs), including 1079 ADRs and 211 MEcs (MEs causing ADE), were reported. Older patients suffered from both ADRs and MEcs (age distribution and dosage form were different between ADRs and MEcs). The main causes of errors were inappropriate usage and dosage of drugs and inappropriate indication selection. Most ADR and MEc cases were mild; the possibility of developing a severe adverse event was quite low. The distribution of the top 10 system and organs, and symptoms involved was significantly different between ADRs and MEcs, with J01 drugs (antibacterials for systemic use) being the leading cause in both. Our results suggested that a direct analysis of data from the spontaneous reporting system is a reliable, and convenient method to investigate MEs and ADRs, despite the existing limitations, and contributes to further understanding the current situation of MEs and ADRs in China.     

Adverse drug reactions related to drugs used in orthostatic hypotension: a prospective and systematic pharmacovigilance study in France

Objective The aim of the present study was to investigate and characterise adverse drug reactions (ADRs) to drugs used in France for orthostatic hypotension (OH).Methods In this prospective and systematic study, 121 consecutive out-patients suffering from primary (Parkinsons disease, pure autonomic failure, multiple system atrophy, Lewy bodies disease) or secondary (diabetic and non-diabetic peripheral neuropathies) autonomic failure with symptomatic OH requiring pharmacological treatment with at least one drug marketed in France for OH were included together with six patients with refractory neurocardiogenic syncope.Results Of the patients, 85 received a monotherapy—mainly with midodrine (49.4%)—and 42 received various combinations, the association of midodrine and fludrocortisone being the most frequent (66.6%). Of all the 127 patients, 88 suffered from a total of 141 ADRs (1.60 per patient) with no statistical difference in ADR frequency between monotherapy and drug combinations (P>0.05). Among ADRs, 24 (17.0%) were considered as serious and 16 (11.3%) were considered as unexpected, most of them observed with heptaminol.Conclusions This study shows a high frequency of ADRs (especially serious and unexpected ADRs) with antihypotensive drugs. It strongly suggests the need for a better evaluation of the safety profile of antihypotensive drugs and improvement in summary of product characteristics.     

我国药品风险管理计划和药物警戒计划的研究概况

我国的《药物警戒质量管理规范》对药物警戒计划的定位是药品上市后风险管理计划的一部分,与欧盟风险管理计划的理念存在差异。我国将风险管理计划按照上市前后不同阶段进行了区分,上市前称为“临床风险管理计划”,批准上市后将其转化为“药物警戒计划”,而欧盟的风险管理计划关注的一直是药品的临床使用风险,没有进行上市前后的区分。由于我国提出风险管理计划的理念较晚,在早期时很多有药品出口业务的企业当时多数是以欧盟的风险管理计划为参考制定的,所以当我国再提出上市后风险管理计划要求时,很多人会有概念上的混淆。结合欧盟和我国近年来对药品风险管理计划的要求变化,厘清药物警戒计划和风险管理计划之间的区别和联系,以期帮助企业更好地开展上市后风险管理。     

四大国际药物警戒数据库概述及其应用

完善的药物警戒数据库是开展药物警戒活动的核心支柱。目前美国、日本、欧洲、世界卫生组织都建立了较为成熟的药物警戒数据库, 在药物不良反应(ADR)监测、ADR信号挖掘和药物上市后再评价等方面都发挥了重要的作用。本文对上述4大数据库的数据来源、数据获取权限、可获取元素、数据质量控制和数据利用现状等方面进行概述, 为临床开展药物警戒活动、完善我国药物警戒数据库的建设提供参考。     

Adverse drug reactions in hospitalized pediatric patients of Saudi Arabian University Hospital and impact of pharmacovigilance in reporting ADR

ObjectivesChildren are more vulnerable to ADRs, and this susceptibility is compounded due to hospitalization. There is a lack of local data regarding the potential risk of ADRs in hospitalized pediatric patients. Therefore, this study is designed to identify the frequent nature, severity of adverse drug reactions, drugs implicated and factors influencing ADRs.MethodsIntensive monitoring study of ADRs was done in hospitalized pediatric patients of King Abdulaziz University Hospital, Jeddah from January to December 2011, with an analogous retrospective study for the preceding year to determine incidence rate, demographic aspects, causality appraisal, polypharmacy, body organs/systems involved and drugs implicated in ADR. Comparison of the two data was done to determine the impact of pharmacovigilance.ResultsIncidence rate of ADRs in retrospective study was (4.50%) and (8.2%) in prospective study. ADR was more in patients who received 5–6 drugs, which was (15.5%) in retrospective study and (22.1%) in prospective study. Regarding age, it was the highest in patients of 0–1 year of age which was (40.7%) in retrospective study and (38.8%) in prospective study. Anti-infective agents were the most frequently involved in ADR (40.8%) in prospective study and (48.2%) and retrospective study. This study also demonstrated that, there was high susceptibility of the skin to the ADR which was (37%) in retrospective study and (42.9%) in prospective study. None of the ADRs proved to be fatal.ConclusionWell premeditated intensive monitoring approach in pharmacovigilance amplifies the ADR detection, which can persuade healthcare providers into more drug safety.     

Handling of drug safety alerts in the European commmunity

A Rapid Alert procedure for the communication and assessment of serious drug safety hazards within the European Community was initiated in 1988. The procedures adopted by member states, the Commission and the CPMP for handling these alerts are described and the early experience is reviewed.     

The role of data mining in pharmacovigilance

A principle concern of pharmacovigilance is the timely detection of adverse drug reactions that are novel by virtue of their clinical nature, severity and/or frequency. The cornerstone of this process is the scientific acumen of the pharmacovigilance domain expert. There is understandably an interest in developing database screening tools to assist human reviewers in identifying associations worthy of further investigation (i.e., signals) embedded within a database consisting largely of background ‘noise’ containing reports of no substantial public health significance. Data mining algorithms are, therefore, being developed, tested and/or used by health authorities, pharmaceutical companies and academic researchers. After a focused review of postapproval drug safety signal detection, the authors explain how the currently used algorithms work and address key questions related to their validation, comparative performance, deployment in naturalistic pharmacovigilance settings, limitations and potential for misuse. Suggestions for further research and development are offered.     

Comparison of pharmacovigilance algorithms in drug hypersensitivity reactions

Background A firm diagnosis of drug hypersensitivity, because it may re-induce the reaction, is seldom confirmed. Causality assessment algorithms are therefore of interest.Aims The objective of this work was to compare three algorithms in the diagnosis of drug hypersensitivity.Methods Evaluation of 120 clinical histories of drug hypersensitivity was carried out: 60 involving -lactams (50%) and 60 involving non-steroidal anti-inflammatory drugs (50%). Each of these groups of patients underwent a standardised allergy diagnosis, which included a detailed anamnesis, skin tests and, often, provocation tests under strict hospital surveillance. Unaware of the final allergy diagnosis, scores were established for all of the cases and compared using algorithms suggested by Begaud and coworkers [2, 20], Jones [13] and Naranjo et al. [21].Results Although the methods of Jones [13] and Naranjo et al. [21] were perfectly concordant (k=1), no concordance was noted using the Begaud and coworkers [2, 20] method.Conclusions All three algorithms are dissimilar regarding the diagnosis of drug hypersensitivity.     

An overview of the pharmacovigilance system in India

Pharmacovigilance (PV) has witnessed several advancements throughout the world over the past few decades. This review provides an overview of the PV system in India, focusing on the current scenario, its development, the challenges faced, and the interventions suggested for its improvement. The Pharmacovigilance Program of India (PvPI) is playing a major role in gathering drug safety related data and adding it to the WHO database. PvPI fulfills the minimum requirements given by the WHO for any functional national Pharmacovigilance system. The Indian Pharmacopoeia Commission (IPC) is the national coordinating center under PvPI. PV in India relies mainly upon the spontaneous reporting of adverse drug events. The major challenge for PV in India is under-reporting. However, there is an improvement in the number of submitted reports after regular training and awareness programmes, which have been conducted by the IPC. The regular and periodic circulation of the ‘PvPI Newsletter’ by the IPC has also been instrumental in increasing awareness about PV amongst healthcare professionals and patients. The intensification of PV activities in India demands particular attention in health science curricula. Indeed, a change in mindset is necessary for prescribers, patients, regulatory agencies, and pharmaceutical companies.     

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。     

The role of hospital and community pharmacists in pharmacovigilance

In this paper, we give an overview of the role pharmacists actually have and could have in collecting reports of adverse drug reactions (ADRs) and more widely in pharmacovigilance.In the literature, several ways are mentioned in which the pharmacist, both the community pharmacist and the hospital pharmacist, can contribute to the safe use of drugs. In addition to their responsibilities regarding drug dispensing and compliance, they can have a substantial role in ADR reporting.Especially, hospital pharmacists can play a significant role in ADR reporting because the most serious adverse drug events occur in hospitals, and ADRs account for a substantial proportion of hospital admissions.Community pharmacists, however, can also play an important role in ADR reporting. This is, for example, the case in the Netherlands where community pharmacists contribute substantially, both in numbers and in quality of ADR reports.The contribution of the pharmacist to pharmacovigilance should, however, not be limited to ADR reporting. The various pharmaceutical disciplines could also greatly enhance our understanding of the nature of ADRs. If those involved in pharmaceutical disciplines can rise to this challenge, they will significantly help deepen our insights into ADRs.