Knowledge, Perceptions, and Attitudes Regarding Antibiotic Use for Lower Respiratory Tract Infections: Insights from Patients in Sri Lanka.

Antibiotic resistance is an emerging global public health threat. One of the main drivers of this threat is the inappropriate use of antibiotics. In Sri Lanka, antibiotic consumption is increasing, but little is known locally about how patients perceive antibiotics. We conducted a qualitative study to gain a better understanding of the knowledge, perceptions, and attitudes of patients regarding antibiotics and antibiotic resistance. Semi-structured interviews involving 18 patients with lower respiratory tract infection (LRTI) admitted to a large, public tertiary care hospital in southern Sri Lanka were conducted. Interviews were analyzed to identify themes regarding the patients' knowledge of LRTI etiology and treatment, perceptions and attitudes toward LRTI treatment, including antibiotics, and patient-physician communication. Most patients mentioned multiple care visits and the use of multiple pharmaceuticals prior to admission. Patients sought a quick resolution to their ailments and frequently visited several private physicians to obtain a satisfying answer. Self-medication was also common. Patients reused prescriptions for antibiotics, kept antibiotics for later use after prematurely stopping their course of treatment, and bought over-the-counter antibiotics. Patients' knowledge of disease etiology and antibiotics was poor. Only a few patients were aware of antibiotic resistance. Despite the desire to receive more information regarding disease and treatment, patient-provider communication was limited and mainly confined to prescription instructions. This qualitative study performed in Sri Lanka suggests that inappropriate use of antibiotics is a multifactorial problem. To improve antibiotic use, a multifactorial approach that includes educating the public, increasing awareness among physicians, and implementing systems-level changes to restrict access to antibiotics is urgently needed.

Review of FDA Amendments Act Section 921 Experience in Posting Data-mining Results from the FAERS Database.

PURPOSE: Title IX, § 921 of the Food and Drug Administration (FDA) Amendments Act of 2007 requires the FDA to mine data on a regular basis, using its adverse events database, the FDA Adverse Event Reporting System, to identify potential signals of serious risks/new safety information. This review of the FDA's quarterly web-posted results is the first to document the contributions of the program to maintaining the continued safe use of approved pharmaceutical drugs/biologics and the lessons that have emerged from this rich experience. METHODS: Details on proprietary prescription drugs/biologics, generic prescription drugs, and over-the-counter drugs were downloaded from the quarterly posts that begin in first quarter of 2008. Key information was tabulated, including proprietary and generic names of products or classes of products, the identified potential signals of serious risks, the labeling-decision category (updated, no action is necessary at this time, or evaluating the need for regulatory action), the labeling section (Warnings and Precautions, Adverse Reactions, Drug Safety Communications, Contraindications, or Boxed Warnings), and estimated times to updated decisions. FINDINGS: Since the beginning of the FDAAA Section 921 posting requirement, the FDA has posted 555 potential signals of serious risk or new safety information. Of these, there have been 262 posts (47%) that resulted in decisions requiring updated product labeling, 75 posts (14%) that resulted in decisions that no action was necessary, and 218 posts (39%) indicating that the FDA was evaluating the need for regulatory action. Of the 262 posts that required updating one or more sections of a product label, there was a preponderance of Warnings and Precautions, with 172 (66%); followed by Adverse Reactions, with 114 (44%); Drug Safety Communications, 44 (18%); Contraindications, 27 (10%); and Boxed Warnings, 19 (7%). The median times to update decisions were 12 months for Warnings & Precautions, Adverse Reactions, and Boxed Warnings, and 11 months for Contraindications. IMPLICATIONS: Important themes from the present analysis include the following: (1) nearly 80% of posts resulted in updated product labeling; (2) 20% of decisions concerned classes of proprietary and generic drug/biologic products; (3) product-use errors, such as name confusion, continue to be important; (4) the safe use of pharmaceuticals in children is gaining attention but still has a long way to go; and (5) drug-drug interactions are of continuing concern. The FDA Amendments Act § 921 program will continue to have an important place in the future of pharmacovigilance practices.

Investigating Overlap in Signals from EVDAS, FAERS, and VigiBase®.

INTRODUCTION: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and VigiBase® are two established databases for safety monitoring of medicinal products, recently complemented with the EudraVigilance Data Analysis System (EVDAS). OBJECTIVE: Signals of disproportionate reporting (SDRs) can characterize the reporting profile of a drug, accounting for the distribution of all drugs and all events in the database. This study aims to quantify the redundancy among the three databases when characterized by two disproportionality-based analyses (DPA). METHODS: SDRs for 100 selected products were identified with two sets of thresholds (standard EudraVigilance SDR criteria for all vs Bayesian approach for FAERS and VigiBase®). Per product and database, the presence or absence of SDRs was determined and compared. Adverse events were considered at three levels: MedDRA® Preferred Term (PT), High Level Term (HLT), and HLT combined with Standardized MedDRA® Query (SMQ). Redundancy was measured in terms of recall (SDRs in EVDAS divided by SDRs from any database) and overlap (SDRs in EVDAS and at least one other database, divided by SDRs in EVDAS). Covariates with potential impact on results were explored with linear regression models. RESULTS: The median overlap between EVDAS and FAERS or VigiBase® was 85.0% at the PT level, 94.5% at the HLT level, and 97.7% at the HLT or SMQ level. The corresponding median recall of signals in EVDAS as a percentage of all signals generated in all three databases was 59.4%, 74.1%, and 87.9% at the PT, HLT, and HLT or SMQ levels, respectively. The overlap difference is partially explained by the relative number of EU cases in EudraVigilance and the ratio of EVDAS cases and FAERS cases, presumably due to differences in marketing authorizations, or market penetration in different regions. Products with few cases in EVDAS (< 1500) also display limited recall of signals relative to FAERs/VigiBase®. Time-on-market does not predict signal redundancy between the three databases. The choice of the DPA has an expected but somewhat small effect on redundancy. CONCLUSIONS: Organizations typically consider regulatory expectations, operating performance (e.g., positive predictive value), and procedural complexity when selecting databases for signal management. As SDRs can be seen as a proxy of general reporting characteristics identifiable in a systematic screening process, our results indicate that, for most products, these characteristics are largely similar in each of the databases.

Comparative Assessment of the National Pharmacovigilance Systems in East Africa: Ethiopia, Kenya, Rwanda and Tanzania.

INTRODUCTION: The increased access to medicinal products in Africa is not well-matched with the pharmacovigilance capacity to monitor drug safety. The objective of this study was to assess the functionality and identify the strengths and limitations of the national pharmacovigilance systems in Ethiopia, Kenya, Rwanda, and Tanzania, and compare these systems. METHODS: Legal and statutory documents governing the pharmacovigilance systems of each participating country were examined by assessors prior to on-site review. The staff of the pharmacovigilance unit of the National Medicines Regulatory Authorities (NMRAs) were interviewed using the East African Community Harmonized Pharmacovigilance Indicators tool, supplemented with indicators from the World Health Organization (WHO) Global Benchmarking Tool. Responses were recorded, and data were analyzed. RESULTS: The pharmacovigilance systems were supported by law and regulations in line with international standards. Standard operating procedures for receiving, processing, and communicating suspected adverse event reports were in place, but reporting of suspected medicine-related harm from stakeholders was inadequate in all countries. The number of Individual Case Safety Reports (ICSRs) received by NMRAs in Kenya, Ethiopia, and Tanzania (mainland) were 35.0, 6.7, and 4.1 per million inhabitants, respectively, in the last calendar year. At the time of assessment, Rwanda did not have an operational system. Overall, ≤ 1% of the total number of health facilities per country submitted ICSRs. Only Kenya and Tanzania had a designated budget for pharmacovigilance activities and an electronic ICSR reporting system. The national pharmacovigilance systems in all four countries did not have access to data on drug utilization. CONCLUSIONS: The national pharmacovigilance systems in the four East African countries have policy and legal frameworks defined by law and regulation to conduct pharmacovigilance activities. However, the four national pharmacovigilance systems are at different levels of capacity and performance with respect to conducting pharmacovigilance activities. Targeted interventions are needed to strengthen the pharmacovigilance systems to enable evidence-based decision making for patient safety.

Drug Safety Evaluation in China.

PURPOSE OF REVIEW: This review aimed to introduce the regulations management and current situations of drug safety evaluation in China. RECENT FINDINGS: The nationwide implementation of good laboratory practice and good clinical practice guarantees the quality of pre-marketing drug safety evaluation. In recent years, post-marketing drug safety monitoring is changing from passive mode to the combination of active and passive monitoring. A national adverse drug reaction monitoring sentinel alliance has been created to actively identify, report, and evaluate adverse reactions, with more than 1.4 million cases reported in 2017. But the quality of the reports is not optimal, with few reports from drug manufacturers, low rate of severe reports, and trend of lag reporting. Drug safety evaluation in China is transitioning from passive monitoring to a combination mode. Drug pharmacovigilance is a powerful tool for active monitoring, but participation by drug manufacturers would be essential to an effective drug safety evaluation system.

Secret safety warnings on medicines: A case study of information access requests.

PURPOSE: There has been less attention to the transparency of postmarket evidence of harmful effects of medicines than of premarket clinical trial data. This is a case study of requests for Australian "direct health professional communications" (DHPCs). These letters are used by regulators and manufacturers to inform clinicians of emergent evidence of harm. DHPCs are not made public by Australia's Therapeutic Goods Administration (TGA). METHODS: We requested all DHPCs sent out in Australia from 2007 to 2016 inclusive for 207 drugs that were subject to safety advisories over this decade in Canada, the United Kingdom, and/or the United States. We contacted 39 manufacturers (February to May 2018), with repeat requests to nonrespondents, and a follow-up freedom-of-information (FOI) request to the TGA. RESULTS: Fifteen companies provided information, either sending DHPCs (n = 4, on five drugs) or affirming none were sent out (n = 11). The remaining 24 of 39 (62%) companies did not provide DHPCs: nine (23%) refused the request, often citing commercial confidentiality; the rest provided no answer despite repeat requests. In total, we had no information for 170 of 207 (82%) of the drugs. Our FOI request to the TGA was unsuccessful. CONCLUSIONS: Our experience highlights unacceptable secrecy concerning safety warnings previously sent to thousands of Australian clinicians. In the absence of explicit regulatory policy supporting disclosure, companies differed in their response. These letters warn of serious and often life-threatening harm and guide safer care; full ongoing public access is needed, ideally in searchable online databases.

Harmonization of Pharmacovigilance Regulation in Brazil: Opportunities to Improve Risk Communication.

Brazilian pharmacovigilance regulations involve 3 spheres: health services, Marketing Authorization Holders (MAHs), and sanitary agency. Drug tolerability began to be effectively assessed in Brazil after the founding of the National Agency of Sanitary Surveillance, which developed the Sentinel Network Project. The objective of the Sentinel Network Project is to increase the adverse drug reaction (ADR) reporting rate by health care professionals in the hospital setting. Pharmacovigilance practices became mandatory for MAHs, and patient tolerability issues were considered in drug policy in Brazil only as recently as 2000. However, despite recent events, the regulatory advancements in pharmacovigilance in Brazil are only equivalent to international practices (ie, those of the European Union). The pharmacovigilance system in the European Union integrates the national authorities, the European Commission, and the European Medicines Agency, which is responsible for the scientific evaluation, supervision, and safety monitoring of medicines for human and veterinary use in the European Union. Furthermore, ADR patient reporting is included in the new EU pharmacovigilance regulations. Numerous possible ways are available to improve the Brazilian pharmacovigilance system, mainly through regulations of biosimilar, nanotechnology, and veterinary medicines or by training health care professionals and patients to report nonserious cases and quality deviations. It is necessary to encourage and develop strategies for decentralizing pharmacovigilance actions in the whole country, as is common practice in several EU countries. Motivating and considering ADR reports by patients and improving feedback and audit practices in health care services and MAHs are also necessary measures. With the inclusion of Brazil as a member of the International Conference of Harmonization, significant changes in pharmacovigilance regulation are expected; these updates, which will consider international standards, will improve signal detection and risk communication.

Evaluation of the Implementation of Additional Risk Minimization Activities in Europe, the USA, and Japan.

BACKGROUND: Risk minimization activities are planned and conducted as part of a drug's risk management plan; additional risk minimization activities are implemented as needed in consideration of the regulations and medical environment in each country/region, as well as drug-specific factors. OBJECTIVE: The present study was conducted with the aim of investigating the status of implementing additional risk minimization activities in Europe, the USA, and Japan and understanding the characteristics of such activities commonly conducted in these countries/regions. METHODS: For new drugs approved between 2013 and 2017, the status of implementing the additional activities was investigated based on the information published on each of the regulatory agencies' websites. Next, we identified drugs approved in all three countries/regions and investigated drug-specific factors such as indications and safety concerns. Furthermore, the contents of the activities were analyzed from the viewpoint of whether they intended risk mitigation or risk prevention. RESULTS: The status of implementing additional activities was 26.4% (42/159 drugs) in Europe, 7.6% (15/197 drugs) in the USA, and 64.8% (92/142 drugs) in Japan. Forty-five drugs that were approved in all three countries/regions were identified. Many drugs with additional activities displayed novel mechanisms of action in therapeutic areas such as oncology. Common additional activities were implemented for only three drugs and for two of these drugs, "teratogenicity" was identified as a safety concern subjected to additional activities. CONCLUSIONS: Risk minimization activities were considered to be largely influenced by differences in regulatory thinking, medical systems, such as the number of healthcare providers per patient and the insurance system, and cultural differences. For drugs with a risk for teratogenicity and those with side effects that differ from conventional therapies, there was a tendency to commonly implement additional activities.

Anatomy of Risk Evaluation and Mitigation Strategies (REMS).

This Chapter provides an introduction and overview of the U.S. FDA REMS program and applicable regulatory aspects. Topics covered include the 2015 Draft Guidance, organization structure and functions, a discussion on pharmacovigilance and adverse event reports, and a discussion of the applicability of REMS in oncology.

Effect of Lawyer-Submitted Reports on Signals of Disproportional Reporting in the Food and Drug Administration's Adverse Event Reporting System.

INTRODUCTION: Lawyer-submitted reports may have unintended consequences on safety signal detection in spontaneous adverse event reporting systems. OBJECTIVE: Our objective was to assess the impact of lawyer-submitted reports primarily for one adverse event (AE) on the ability to detect a signal of disproportional reporting for another AE for the same drug in the US FDA Adverse Event Reporting System (FAERS). METHODS: FAERS reports from January 2004 to September 2015 were used to estimate yearly cumulative proportional reporting ratios (PRRs) for three known drug-AE pairs-isotretinoin-birth defects, atorvastatin-rhabdomyolysis, and rosuvastatin-rhabdomyolysis-with and without lawyer-submitted reports. Isotretinoin and atorvastatin have been the subject of high-profile tort litigation regarding other AEs. A lower bound of the 95% confidence interval (CI) of one or more based on three or more reports defined a signal. RESULTS: Cumulative PRRs met signaling criteria in all analyses. For isotretinoin, lawyer-submitted reports increased PRRs for birth defects before 2008, with the largest increase in 2006 (2.9 [95% CI 2.4-3.5] to 3.3 [95% CI 2.8-3.9]); lawyer-submitted reports decreased PRRs for birth defects after 2011, with the largest decrease in 2013 (2.2 [95% CI 2.0-2.5] to 1.9 [95% CI 1.7-2.1]). For atorvastatin, lawyer-submitted reports reduced PRRs for rhabdomyolysis after 2013, with the largest decrease in 2015 (18.0 [95% CI 17.1-19.1] to 15.4 [95% CI 14.5-16.2]). Lawyer-submitted reports had little impact on PRRs for rosuvastatin and rhabdomyolysis. CONCLUSIONS: Inclusion of lawyer-submitted reports in FAERS did not meaningfully distort known safety signals for two drugs subject to high-profile tort litigation for other AEs.

Evolution and key elements of the Brazilian pharmacovigilance system: a scoping review beginning with the creation of the Brazilian Health Regulatory Agency. / Evolução e elementos-chave do sistema de farmacovigilância do Brasil: uma revisão de escopo a partir da criação da Agência Nacional de Vigilância Sanitária.

This scoping review aims to describe and characterize the Brazilian pharmacovigilance system Brazil (SINAF) and verify to what extent it meets the minimum requirements proposed by the World Health Organization for the functional performance of this type of national system. The literature search strategy used STARLITE recommendations and search terms in MEDLINE/PubMed, Google, the Brazilian National Press, and the website of the Brazilian Health Regulatory Agency (Anvisa), from 1999, when Anvisa was created, to March 2016. The review included 47 publications (4.4%), out of a total of 1,068 identified, in the following order: 14 legal provisions (29.8%), 13 (27.6%) technical documents, and 10 (21.3%) scientific articles. The studies and technical documents covered the creation of the first pharmacovigilance technical unit at the federal level, the reporting system for adverse events, the National Monitoring Center, and the Technical Chambers on Medications. The reporting rate for adverse drug events in Brazil in 2013 was 36 reports per million inhabitants, considerably lower than the target proposed in the international literature, which suggests 300 reports per million inhabitants. This study identified structural and functional aspects that can compromise the performance of SINAF, such as lack of legislation officially establishing the system itself and its objectives.

Esta revisão de escopo objetiva descrever e caracterizar o sistema de farmacovigilância do Brasil (SINAF) e averiguar o atendimento aos requisitos mínimos propostos pela Organização Mundial da Saúde para um desempenho funcional de sistemas nacionais dessa natureza. A estratégia de pesquisa bibliográfica utilizou recomendações do STARLITE e termos de busca nas bases de dados MEDLINE/PubMed, Google, Imprensa Nacional da República do Brasil e website da Agência Nacional de Vigilância Sanitária (Anvisa), compreendendo o período entre 1999, ano de criação da Anvisa, e março de 2016. Foram incluídas 47 (4,4%) publicações, de um total de 1.068 identificadas, prevalecendo, nesta ordem: 14 normas jurídicas (29,8%), 13 (27,6%) documentos técnicos e 10 (21,3%) artigos científicos. Os estudos e documentos técnicos analisados compreenderam a criação, em âmbito federal, da primeira unidade técnica de farmacovigilância do sistema de notificação de eventos adversos, o Centro Nacional de Monitorização e a Câmara Técnica de Medicamentos. A taxa de notificação de eventos adversos a medicamentos no Brasil correspondeu, em 2013, a 36 notificações/1 milhão de habitantes, bastante inferior à meta proposta na literatura internacional, que sugere 300 notificações/1 milhão de habitantes. Este estudo identificou aspectos estruturais e funcionais que podem comprometer o desempenho do SINAF, como a falta de legislação que institua oficialmente o próprio sistema e suas finalidades.

Esta revisión de alcance tiene como objetivo describir y caracterizar el sistema de farmacovigilancia de Brasil (SINAF) y constatar su adscripción a los requisitos mínimos propuestos por la Organización Mundial de la Salud, respecto al desempeño funcional de los sistemas nacionales de esta naturaleza. La estrategia de investigación bibliográfica utilizó recomendaciones del STARLITE y términos de búsqueda en las bases de datos MEDLINE/PubMed, Google, Imprenta Nacional de la República de Brasil y de la página web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa), comprendiendo el período entre 1999, año de creación de la Anvisa, y marzo de 2016. Se incluyeron 47 (4,4%) publicaciones, de un total de 1.068 identificadas, predominando por este orden: 14 normas jurídicas (29,8%), 13 (27,6%) documentos técnicos y 10 (21,3%) artículos científicos. Los estudios y documentos técnicos analizados incluyeron la creación, en el ámbito federal, de la primera unidad técnica de farmacovigilancia del sistema de notificación de eventos adversos, el Centro Nacional de Monitoreo y la Cámara Técnica de Medicamentos. La tasa de notificación de eventos adversos en medicamentos dentro de Brasil correspondió, en 2013, a 36 notificaciones/1 millón de habitantes, bastante inferior a la meta propuesta en la literatura internacional, que sugiere 300 notificaciones/1 millón de habitantes. Este estudio identificó aspectos estructurales y funcionales que pueden comprometer el desempeño del SINAF, como la falta de legislación que instituya oficialmente al propio sistema y sus finalidades.

Evolução e elementos-chave do sistema de farmacovigilância do Brasil: uma revisão de escopo a partir da criação da Agência Nacional de Vigilância Sanitária / Evolución y elementos-clave del sistema de farmacovigilancia de Brasil: una revisión de alcance a partir de la creación de la Agencia Nacional de Vigilancia Sanitaria / Evolution and key elements of the Brazilian pharmacovigilance system: a scoping review beginning with the creation of the Brazilian Health Regulatory Agency

Esta revisão de escopo objetiva descrever e caracterizar o sistema de farmacovigilância do Brasil (SINAF) e averiguar o atendimento aos requisitos mínimos propostos pela Organização Mundial da Saúde para um desempenho funcional de sistemas nacionais dessa natureza. A estratégia de pesquisa bibliográfica utilizou recomendações do STARLITE e termos de busca nas bases de dados MEDLINE/PubMed, Google, Imprensa Nacional da República do Brasil e website da Agência Nacional de Vigilância Sanitária (Anvisa), compreendendo o período entre 1999, ano de criação da Anvisa, e março de 2016. Foram incluídas 47 (4,4%) publicações, de um total de 1.068 identificadas, prevalecendo, nesta ordem: 14 normas jurídicas (29,8%), 13 (27,6%) documentos técnicos e 10 (21,3%) artigos científicos. Os estudos e documentos técnicos analisados compreenderam a criação, em âmbito federal, da primeira unidade técnica de farmacovigilância do sistema de notificação de eventos adversos, o Centro Nacional de Monitorização e a Câmara Técnica de Medicamentos. A taxa de notificação de eventos adversos a medicamentos no Brasil correspondeu, em 2013, a 36 notificações/1 milhão de habitantes, bastante inferior à meta proposta na literatura internacional, que sugere 300 notificações/1 milhão de habitantes. Este estudo identificou aspectos estruturais e funcionais que podem comprometer o desempenho do SINAF, como a falta de legislação que institua oficialmente o próprio sistema e suas finalidades.

Esta revisión de alcance tiene como objetivo describir y caracterizar el sistema de farmacovigilancia de Brasil (SINAF) y constatar su adscripción a los requisitos mínimos propuestos por la Organización Mundial de la Salud, respecto al desempeño funcional de los sistemas nacionales de esta naturaleza. La estrategia de investigación bibliográfica utilizó recomendaciones del STARLITE y términos de búsqueda en las bases de datos MEDLINE/PubMed, Google, Imprenta Nacional de la República de Brasil y de la página web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa), comprendiendo el período entre 1999, año de creación de la Anvisa, y marzo de 2016. Se incluyeron 47 (4,4%) publicaciones, de un total de 1.068 identificadas, predominando por este orden: 14 normas jurídicas (29,8%), 13 (27,6%) documentos técnicos y 10 (21,3%) artículos científicos. Los estudios y documentos técnicos analizados incluyeron la creación, en el ámbito federal, de la primera unidad técnica de farmacovigilancia del sistema de notificación de eventos adversos, el Centro Nacional de Monitoreo y la Cámara Técnica de Medicamentos. La tasa de notificación de eventos adversos en medicamentos dentro de Brasil correspondió, en 2013, a 36 notificaciones/1 millón de habitantes, bastante inferior a la meta propuesta en la literatura internacional, que sugiere 300 notificaciones/1 millón de habitantes. Este estudio identificó aspectos estructurales y funcionales que pueden comprometer el desempeño del SINAF, como la falta de legislación que instituya oficialmente al propio sistema y sus finalidades.

This scoping review aims to describe and characterize the Brazilian pharmacovigilance system Brazil (SINAF) and verify to what extent it meets the minimum requirements proposed by the World Health Organization for the functional performance of this type of national system. The literature search strategy used STARLITE recommendations and search terms in MEDLINE/PubMed, Google, the Brazilian National Press, and the website of the Brazilian Health Regulatory Agency (Anvisa), from 1999, when Anvisa was created, to March 2016. The review included 47 publications (4.4%), out of a total of 1,068 identified, in the following order: 14 legal provisions (29.8%), 13 (27.6%) technical documents, and 10 (21.3%) scientific articles. The studies and technical documents covered the creation of the first pharmacovigilance technical unit at the federal level, the reporting system for adverse events, the National Monitoring Center, and the Technical Chambers on Medications. The reporting rate for adverse drug events in Brazil in 2013 was 36 reports per million inhabitants, considerably lower than the target proposed in the international literature, which suggests 300 reports per million inhabitants. This study identified structural and functional aspects that can compromise the performance of SINAF, such as lack of legislation officially establishing the system itself and its objectives.

Enhancing Pharmacovigilance Capabilities in the EU Regulatory Network: The SCOPE Joint Action.

In November 2013, a team of European regulators initiated the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action. Funded by the Health Programme of the European Union, and with contributions from the involved Member States, SCOPE gathered information and expertise on how regulators in Member States run their national pharmacovigilance systems to meet the requirements of the pharmacovigilance legislation that came into effect in June 2012. The SCOPE project evaluated then-current practices and developed tools to further improve the skills and capability in the pharmacovigilance network. The project was divided into eight separate work streams, five of which concentrated on pharmacovigilance topics-collecting information on suspected adverse drug reactions, identifying and managing safety issues (signals), communicating risk and assessing risk minimisation measures, supported by effective quality management systems. The other three work streams focused on the functional aspects-coordination, communication and evaluation of the project. Through the project, SCOPE delivered guidance, training in key aspects of pharmacovigilance, and tools and templates to support best practice. The deliverables provide practical guidance that those working in the European national competent authorities can take to strengthen their national systems. The SCOPE outputs can be useful for other stakeholders involved in pharmacovigilance activities, including the pharmaceutical industry, healthcare professionals, patient and consumer organisations, and academia.

EU pharmacovigilance regulatory requirements of anticancer biosimilar monoclonal antibodies.

An increasing number of innovative oncology monoclonal antibodies (mAbs) have been introduced into the global market, and biosimilar versions have now also been approved in Europe. Being complex to develop and difficult to manufacture, the biosimilar is a drug similar but not identical in physicochemical characteristics, efficacy, and safety to an original biological drug already approved in the European Union, for which marketing exclusivity rights have expired. Generally, the safety monitoring of biosimilars follows the same requirements that apply to all biologicals, even if specific pharmacovigilance measures exist and some of them are still being debated. The manufacturing process, immunogenicity, traceability, and extrapolation of indication are keywords which may impact on the achievement of additional knowledge about the safety of a biosimilar mAb. In this article, we aim to discuss elements that play a central role in the pharmacovigilance legislation of biosimilar mAbs.

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.

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.

Is pharmacovigilance of biologicals cost-effective?

Pharmacovigilance is an essential part of the post-marketing surveillance of new biologicals. It not only requires a substantial investment of the marketing authorization holder but also of the clinical field to provide accurate safety information. Hence, does pharmacovigilance delivers value for money? This important question needs to be discussed in the light of regulatory requirements, value and cost.

Pharmacovigilance in developing countries (part II): a path forward.

In recent years, attention to pharmacovigilance has gained momentum in developing countries, however awareness of, and policies or systems for pharmacovigilance in most developing countries still lags sharply behind developed countries. This article proposes different strategies to encourage the introduction and sustain the advancement of robust pharmacovigilance systems in developing countries. To this end, this article seeks to accomplish the ultimate goal of pharmacovigilance in a developing country context; ensuring patient safety and promoting safe and rational use of drugs.