European Network Of Centres For Pharmacoepidemiology And Pharmacovigilance Research Articles

Comparing regulatory guidance on risk minimization/mitigation and the Reporting recommendation Intended for pharmaceutical Risk Minimization Evaluation Studies checklist.

The latest country-specific regulatory guidance for assessing effectiveness of risk minimization measures (RMM) strategies was identified across five continents-Africa (Egypt, South Africa), Asia (Australia, China, Japan, South Korea, Singapore), Europe (EU-27, United Kingdom), North America (Unites States, Canada) and South America (Brazil)-and compared to the Reporting recommendation Intended for pharmaceutical Risk Minimization Evaluation Studies (RIMES) checklist, developed to assess the quality of effectiveness evaluations and endorsed by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). RIMES checklist items address study hypothesis, participants, measures, statistical analysis and results. European Medical Agency (EMA) and Food and Drug Administration (FDA) guidance only partially aligned with RIMES, primarily for measures and results. In the absence of country-specific guidance, most countries recommended following EMA or FDA guidelines; Japan and South Africa mentioned the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH E2E) guideline; Brazil and China had no guidance/recommendations. Worldwide, there was a lack of RMM-specific guidance and, when guidance existed, they were not harmonized, and alignment with the RIMES checklist was limited.

Social determinants of health associated with COVID-19 severity during pregnancy: a multinational cohort study (in the International Registry of Coronavirus Exposure in Pregnancy)

BackgroundThe COVID-19 pandemic has caused morbidity and mortality, particularly among vulnerable populations. We aimed to assess social and demographic characteristics associated with COVID-19 severity among symptomatic participants during pregnancy.MethodsThe International Registry of Coronavirus Exposure in Pregnancy is a multinational, longitudinal observational cohort study of adult participants tested for SARS-CoV-2 or who received clinical diagnosis of COVID-19 during pregnancy (NCT04366986). Disease severity status of mild, moderate, or severe was determined based on symptoms and healthcare utilization. Stratified by current versus recent pregnancy at enrollment, univariate mixed-effects logistic regression modeling was used to characterize association between social and demographic characteristics with COVID-19 severity, using a cumulative mixed effect model with country as a random effect.ResultsThe odds of developing more severe COVID-19 (odds ratio [95% confidence interval]) were higher among participants with lower socioeconomic status (poor: 2.72 [2.01,3.69]; lower-middle class: 2.07 [1.62,2.65] vs wealthy), among participants with lower educational attainment (high school: 1.68 [1.39,2.03]; < high school (1.77 [1.25,2.51] vs graduate education). Participants over 25 years of age had lower odds of severe COVID-19 versus participants < 25 years (25–34: 0.69 [0.56,0.85]; 35–50: 0.62 [0.48,0.80]). Employment in food services was also associated with increased odds of more severe COVID-19, whereas employment in healthcare and within home, and primiparity were associated with lower severity.ConclusionsFindings suggest that employment setting and economic status have strong associations with COVID-19 severity, which warrants considering social determinants of health in the context of assessing risk factors of more severe COVID-19 during pregnancy.Trial registrationIRCEP was registered with the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) [EUPAS37360] and clinicaltrials.gov [NCT04366986].

Healthcare Resource Utilization and Costs for Empagliflozin Versus Glucagon-Like Peptide-1 Receptor Agonists in Routine Clinical Care in Denmark.

The sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin has shown reductions in major adverse cardiac events similar to glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, evidence is limited about how these therapies compare regarding overall healthcare resource utilization and costs in routine clinical care. We conducted a comparative cohort study based on linked prospective healthcare databases for the entire population of Denmark during 2015-2018. We included 13,747 new users of empagliflozin and 13,249 new users of GLP-1RAs. Propensity scores were applied to balance potential confounders across the two treatment groups through inverse probability treatment weighting (IPTW). We assessed directly referable costs per person-year associated with healthcare resource utilization (inpatient, emergency room, and outpatient clinic hospital care, primary care health services, and prescription medication costs at pharmacies) among drug initiators while on-treatment. The two IPTW cohorts were well balanced at baseline (median age 61years, 60% men, diabetes duration 6.7years, 19% with pre-existing ischemic heart disease, 8% with pre-existing cerebrovascular disease), with similar healthcare costs in the previous year. During follow-up, average on-treatment costs per person-year were very similar among empagliflozin and GLP-1 RA initiators for the following services: inpatient hospitalizations (13,565 DKK versus 13,275 DKK), hospital outpatient clinic visits (12,007 DKK versus 12,152 DKK), emergency room visits (370 DKK versus 399 DKK), and primary care services (4108 DKK versus 4302 DKK). Total costs for any prescription drugs were clearly lower for empagliflozin initiators than for GLP-1 RA initiators (8946 DKK versus 14,029 DKK). In sum, overall healthcare costs on-treatment were lower for empagliflozin initiators (38,995 DKK per person-year) than for GLP-1RA initiators (44,157 DKK per person-year). In this nationwide population-based cohort study, average healthcare costs after drug initiation and while on treatment were lower for empagliflozin initiators than for GLP-1RAs initiators, driven by lower drug costs. The study protocol and analysis plan have been registered on the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) ( http://www.encepp.eu/encepp/viewResource.htm?id=37726 , first protocol registration 4 June 2019), and on clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT03993132 , first posted 20 June 2019).

Pharmacovigilance in juvenile idiopathic arthritis patients treated with biologic or synthetic drugs: combined data of more than 15,000 patients from Pharmachild and national registries

BackgroundThe availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden.MethodsDescriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available.ResultsData from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1–6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor–negative polyarthritis (range of 24.6–29.9%). Methotrexate (61–84%) and etanercept (24%–61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7–42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4–30.1%) followed by gastrointestinal disorders (11.5–19.6%). The most frequent ESIs were infections (75.3–89%).ConclusionsThis article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA.Registry registrationThe Pharmachild registry is registered at ClinicalTrials.gov (NCT01399281) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) (http://www.encepp.eu/encepp/viewResource.htm?id=19362). The BiKeR registry is registered at ENCePP (http://www.encepp.eu/encepp/viewResource.htm?id=20591).

A tool for evaluating scientific independence, integrity and transparency in observational studies of vaccine effectiveness

Introduction Observational studies are widely used to evaluate the impact of vaccines. They are being conducted by a variety of institutions and collaborations, including public-private partnerships (PPPs). The European Union promotes PPPs through the Innovative Medicines Initiative (IMI): examples of its vaccine-related IMI PPPs include the ADVANCE and DRIVE consortia (respectively, Accelerated Development of VAccine benefit–risk Collaboration in Europe & Development of Robust and Innovative Vaccine Effectiveness). However, practices and attitudes towards PPPs in the public health field differ, and concerns over their scientific independence have been put forth. While there have been efforts to evaluate and strengthen the methodology and reporting of observational studies, clear and comprehensive guidelines on how to evaluate their scientific independence, integrity and transparency (especially in the presence of diverse governance and funding models) are lacking. Methods A review of existing guidelines touching upon the topics of scientific independence, integrity and/or transparency in the context of observational studies was performed (consisting of a literature search and screening of the reference lists of retrieved documents). Key indicators of scientific independence, integrity and transparency were identified with the focus on relevance and measurability. Based on these, a checklist for evaluating individual studies and study protocols has been compiled. Results Several guidelines include recommendations on topics related to scientific independence, integrity and transparency that can be applied to observational studies of vaccines’ impact. The ADVANCE Code of Conduct was selected as the pivotal reference as it already considered relevant guidelines during its preparation; examples of these include the International Epidemiological Association's Good Epidemiological Practice (GEP) and the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) Checklist for Study Protocols. We present an overview of the various definitions and principles, as well as a checklist-based tool for evaluating the scientific independence, integrity and transparency of observational studies. The tool can be applied by independent reviewers to assess studies retrospectively as well as by study teams to inform the planning of new ones. Conclusions Questions of scientific independence, integrity and transparency are central in evaluating evidence from observational studies of vaccines. Our tool aims to provide a systematic way to address these topics; the next step will be to validate it in relation to existing protocols.

Strengthening standards, transparency, and collaboration to support medicine evaluation: Ten years of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP).

Strengthening standards, transparency, and collaboration to support medicine evaluation: Ten years of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP).

An analysis of characteristics of post-authorisation studies registered on the ENCePP EU PAS Register.

Background: The objective of this study was to investigate the study design characteristics of Post-Authorisation Studies (PAS) requested by the European Medicines Agency which were recorded on the European Union (EU) PAS Register held by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Methods: We undertook a cross-sectional descriptive analysis of all studies registered on the EU PAS Register as of 18 thOctober 2016. Results: We identified a total of 314 studies on the EU PAS Register, including 81 (26%) finalised, 160 (51%) ongoing and 73 (23%) planned. Of those studies identified, 205 (65%) included risk assessment in their scope, 133 (42%) included drug utilisation and 94 (30%) included effectiveness evaluation. Just over half of the studies (175; 56%) used primary data capture, 135 (43%) used secondary data and 4 (1%) used a hybrid design combining both approaches. Risk assessment and effectiveness studies were more likely to use primary data capture (60% and 85% respectively as compared to 39% and 14% respectively for secondary). The converse was true for drug utilisation studies where 59% were secondary vs. 39% for primary. For type 2 diabetes mellitus, database studies were more commonly used (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs) whereas for studies in oncology, primary data capture were more likely to be used (85% vs 4% chart review, and 11% database study designs). Conclusions: Results of this analysis show that PAS design varies according to study objectives and therapeutic area.

An analysis of characteristics of post-authorisation studies registered on the ENCePP EU PAS Register

Background: The objective of this study was to investigate the study design characteristics of Post-Authorisation Studies (PAS) requested by the European Medicines Agency which were recorded on the European Union (EU) PAS Register held by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Methods: We undertook a cross-sectional descriptive analysis of all studies registered on the EU PAS Register as of 18 th October 2016. Results: We identified a total of 314 studies on the EU PAS Register, including 81 (26%) finalised, 160 (51%) ongoing and 73 (23%) planned. Of those studies identified, 205 (65%) included risk assessment in their scope, 133 (42%) included drug utilisation and 94 (30%) included effectiveness evaluation. Just over half of the studies (175; 56%) used primary data capture, 135 (43%) used secondary data and 4 (1%) used a hybrid design combining both approaches. Risk assessment and effectiveness studies were more likely to use primary data capture (60% and 85% respectively as compared to 39% and 14% respectively for secondary). The converse was true for drug utilisation studies where 59% were secondary vs. 39% for primary. For type 2 diabetes mellitus, database studies were more commonly used (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs) whereas for studies in oncology, primary data capture were more likely to be used (85% vs 4% chart review, and 11% database study designs). Conclusions: Results of this analysis show that PAS design varies according to study objectives and therapeutic area.

An analysis of characteristics of post-authorisation studies registered on the ENCePP EU PAS Register

The objective of this study was to investigate the study design characteristics of Post-Authorisation Studies (PAS) requested by the European Medicines Agency which were recorded on the European Union (EU) PAS Register held by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). We undertook a cross-sectional descriptive analysis of all studies registered on the EU PAS Register as of 18 th October 2016. We identified a total of 314 studies on the EU PAS Register, including 81 (26%) finalised, 160 (51%) ongoing and 73 (23%) planned. Of those studies identified, 205 (65%) included risk assessment in their scope, 133 (42%) included drug utilisation and 94 (30%) included effectiveness evaluation. Just over half of the studies (175; 56%) used primary data capture, 135 (43%) used secondary data and 4 (1%) used a hybrid design combining both approaches. Risk assessment and effectiveness studies were more likely to use primary data capture (60% and 85% respectively as compared to 39% and 14% respectively for secondary). The converse was true for drug utilisation studies where 59% were secondary vs. 39% for primary. For type 2 diabetes mellitus, database studies were more commonly used (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs) whereas for studies in oncology, primary data capture were more likely to be used (85% vs 4% chart review, and 11% database study designs). Results of this analysis show that study objectives and therapeutic area influence PAS design in terms of type of data capture used.

Postinjection delirium/sedation syndrome in patients with schizophrenia receiving olanzapine long-acting injection: results from a large observational study.

BackgroundPostinjection delirium/sedation syndrome (PDSS) has been reported uncommonly during treatment with olanzapine long-acting injection (LAI), a sustained-release formulation of olanzapine.AimsThe primary aim of the study was to estimate the incidence per injection and per patient of PDSS events in adult patients with schizophrenia who were receiving olanzapine LAI in real-world clinical practice. Secondary aims were to further characterise the clinical presentation of PDSS events, to identify potential risk factors associated with PDSS events and to characterise hospitalisations at baseline and post-baseline.MethodA prospective observational study of adult patients with schizophrenia receiving olanzapine LAI from 24 countries. Data were collected on patient characteristics, olanzapine LAI treatment and any adverse events (AEs). All AEs were reviewed and adjudicated for PDSS using predetermined criteria.ResultsThere were 46 confirmed PDSS events (0.044% of the 103 505 injections) in 45 patients (1.17% of the 3858 patients). Based on 45 confirmed events with time-to-onset information, 91.1% (n=41) occurred within 1 h of injection. Time-to-recovery from the event was within 72 h for 95.6% of patients (range 6 h to 11 days). Risk factors for PDSS (per-injection) included high dose (odds ratio (OR)high/low=3.95; P=0.006) and male gender (ORfemale/male=0.42; P=0.017).ConclusionsResults of this study confirm previously reported PDSS rates, time to onset and recovery, and the severity of PDSS events, and suggest that higher doses and male gender are potential risk factors associated with PDSS.Declaration of interestAll authors are full-time employees and hold stock/stock options in Eli Lilly, which funded this study. This post-authorisation safety study (PASS) was proposed by Eli Lilly when submitting the original marketing authorisation application for olanzapine LAI in 2007. The protocol and final study report for this European Union regulatory commitment are publicly accessible via the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) European Union PASS Register (www.encepp.eu/encepp/viewResource.htm?id=16847). The current manuscript describes the results within the final study report.Copyright and usage© The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Best Practices and Innovations for Managing Codeine Misuse and Dependence.

Promoting and ensuring safe use of codeine containing medicines remains a public health issue given the rise in reporting of misuse and dependence particularly in countries where available over-the-counter (OTC). The aim of this unique study was to identify best practices in management of opioid abuse and dependence, particularly codeine, and innovations to meet challenges surrounding safe and compliant use, patient awareness-raising, reducing health harms and enhancing successful treatment of dependence. A mixed methods approach using three data points was used that included : (1) analysis of data from existing scoping reviews to identify potential areas for innovation (2) interviews with key national stakeholders from public health, pharmaceutical, regulatory, primary care and addiction practice in three distinct regulatory regimes (Ireland, United Kingdom and South Africa); and (3) a circular email request for information on potential innovations to members of the European Medicine's Agency European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP). Data from these three sources were analysed to identify best practices and opportunities for innovation. Best practices and potential innovations were identified under the nine headings: (1) manufacture; (2) product information and public education; (3) responsible prescribing; (4) monitoring and surveillance; (5) dispensing, screening and brief interventions in community pharmacies; (6) safety in the workplace and on the road; (7) internet supply of codeine and online support; (8) treatment of codeine dependence; and (9) learning resources and training for health professionals. Challenges ensuring availability of codeine containing medicines for legitimate therapeutic use, while minimising misuse, dependence and related health harms warrant consideration of new innovations. Most promising innovative potential lies across the products' retail lifecycle from manufacture to prescriber and community pharmacy practitioner.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

PRM229 - Do We Need to Strengthen Study Design in Observational Studies?

Guidance and standards are made available by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) as reference tools for methodology and transparency of post-authorization studies. They are cited by the Guideline on good pharmacovigilance practices (GVP) Module VIII as relevant scientific guidances. Here we report an analysis conducted on Pharmacovigilance Risk Assessment Committee (PRAC) minutes regarding methodological issues. All publicly available minutes of PRAC meetings from July 2012 to March 2015 were considered. The number of submitted post-authorization safety study (PASS) protocols requiring endorsement was recorded (excluding advices), as well as endorsement/ refusal and reason. ENCePP documentation was consulted. From July 2012 to March 2015, 33 PASS protocols submitted to PRAC requiring endorsement were considered, increasing with years: 2 in 2012, 8 (17 considering resubmissions) in 2013, 18 (24 considering resubmissions) in 2014. The total number of evaluations was 54. Thirteen were endorsed at the first step (including endorsement with changes requested), while 20 required at least one amendment reaching approval up to 15 months after submission. The most common reasons for refusal concerned study design (20 cases), mainly reporting designs not allowing to fulfil study objectives (N=14). Furthermore, PRAC review asked for alternatives to reduce bias and confounding (N=2), simplifications aiming at reinforcing the observational nature of the study (N=1), further justification of sample size (N=1) and considerations on feasibility (N=1). From 2013 to 2014 an increasing number of endorsed PASS protocols was observed (7/17 and 12/24 respectively). During the same years ENCePP Checklist for Study Protocols and ENCePP Guide on Methodological Standards in Pharmacoepidemiology were reviewed, and the number of studies included in the ENCePP e-register increased. An increasing use of guidance and standards will allow strengthening robustness of design and results of observational studies.

Benefits of large healthcare databases for drug risk research

Large electronic healthcare databases have become an important worldwide data resource for drug safety research after approval. Signal generation methods and drug safety studies based on these data facilitate the prospective monitoring of drug safety after approval, as has been recently required by EU law and the German Medicines Act. Despite its large size, a single healthcare database may include insufficient patients for the study of a very small number of drug-exposed patients or the investigation of very rare drug risks. For that reason, in the United States, efforts have been made to work on models that provide the linkage of data from different electronic healthcare databases for monitoring the safety of medicines after authorization in (i) the Sentinel Initiative and (ii) the Observational Medical Outcomes Partnership (OMOP). In July 2014, the pilot project Mini-Sentinel included a total of 178million people from 18 different US databases. The merging of the data is based on a distributed data network with a common data model. In the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) there has been no comparable merging of data from different databases; however, first experiences have been gained in various EU drug safety projects. In Germany, the data of the statutory health insurance providers constitute the most important resource for establishing a large healthcare database. Their use for this purpose has so far been severely restricted by the Code of Social Law (Section 75, Book 10). Therefore, a reform of this section is absolutely necessary.

Pioglitazone, bladder cancer, and detection bias (吡格列酮、膀胱癌以及检验偏差)

In their review of diabetes and cancer, Wang et al.1 have brought to our attention the 8-year interim analysis of the Kaiser Permanente Northern California (KPNC) cohort study of pioglitazone and bladder cancer,2 and the finding that adjusting for albuminuria attenuated the risk estimates. New additional analyses from the KPNC investigators have been posted to the European Medicines Agency's European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) website and indicate the association may have been due to detection bias.3 It was found that there was more urinary monitoring for albuminuria among pioglitazone-treated patients, resulting in increased detection of subclinical hematuria and leading to a detection bias for bladder cancer. Adjusting for monitoring for albuminuria shifted the KPNC risk estimate to the null. No previous observational studies of pioglitazone had considered this detection bias. A recent Canadian cohort study has similarly suggested that an increased frequency of physician visits (e.g. to intensify monitoring or switch diabetic medications) may lead to the discovery of undiagnosed bladder cancer and result in a detection bias for bladder cancer in observational studies of diabetic patients.4

PHP226 - Introducing the ENCePP Working Group (WG) on Health Technology Assessment (HTA): Enhancing the Generation of Additional Evidence for HTA Processes

The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) is a project led by the European Medicines Agency aimed at further strengthening the post-authorisation monitoring of medicinal products in Europe by facilitating the conduct of multi-centre, independent post-authorisation studies focusing on safety and benefit/risk assessment. ENCePP has recently established a WG on HTA to develop methodological guidance to supplement the efficacy and safety aspects of medicines known at the time of marketing authorisation (MA) and to bridge the needs of HTA and post-marketing benefit-risk assessments. Decision makers are often faced with the challenge that long-term, real-world data on safety and effectiveness is lacking at the time of MA. This creates uncertainty around the medicines' risk-benefit profile while manufacturers, health care providers, and patient groups exert pres sure by demanding early decisions and rapid access. Decision makers may unduly delay potential benefits to patients by waiting for stronger evidence, or may endorse medicines that later turn out to have a less robust benefit-risk ratio, to be ineffective cost-ineffective, or even harmful. Hence, many countries have developed mechanisms that allow temporary access to promising medicines while concurrently requesting the generation of additional evidence to reduce uncertainty. Their objective is an optimal trade-off between different stakeholder needs, flexibility, responsiveness, and rigor as well as the flexibility to revise decisions on access when new evidence becomes available. The ENCePP WG on HTA has the potential to become a capacity building tool for regulatory and HTA agencies to develop research structures aimed at complementing the evidence generation for MA and market access. Post-authorisation studies developed under the auspices of ENCePP could provide new safety and clinical effectiveness information of marketed medicines. ENCePP expertise, research experience and health care databases may also contribute to the coordination, methodological guidance and data sourcing for the enhancement of HTA processes.

Translation and introduction of Guide to Methodological Standards in Pharmacoepidemiology

Post-marketing pharmacovigilance of drugs has become one of the most important activities for regulatory authorities. In China, pharmacovigilance is currently receiving the attention of government, pharmaceutical industries and the public. In order to support high quality pharmacoepidemiological studies and to stimulate innovation that benefits patients and the wider public, the European medicines agency (EMA) organized the European network of centres for pharmacoepidemiology and pharmacovigilance (ENCePP) to formulate and publish the Guide on Methodological Standards in Pharmacoepidemiology as a reference document for the methodological standards of pharmacovigilance activities in the European union (EU). It supplies methodological and scientific guidance, and advises on technical aspects of conducting parmacoepidemiological studies and undertaking parmacovigilance. As advice includes: legal and ethical requirements, general aspects of study protocols, research questions, approaches to data collection, study designs and methods, statistical and epidemiological analysis plans, quality control and quality assurance, reporting of adverse events to regulatory authorities, communication of findings, and so on. The translation and introduction of this guidance can provide a useful technical and methodological reference for us to carry out the pharmacovigilance (especially for parenterally administered Chinese medicine safety monitoring).

ENCePP: Strengthening methodology, transparency and independence

The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP), coordinated by the European Medicines Agency, has seen rapid growth in recent years and now accounts for >170 partner organizations, including research centers, therapeutic networks, and data source owners. The increase in pharmacoepidemiology research via networks such as ENCePP is a clear trend to make best use of available data and expertise, through the conduct of high-quality, independent, and transparent studies focusing on safety and on benefit/risk.

Increasing scientific standards, independence and transparency in post‐authorisation studies: the role of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance

PURPOSE: The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP), an initiative coordinated by the European Medicines Agency, aims to build capacity for and increase trust in post-authorisation studies to further support medicine decision making. METHODS: ENCePP seeks to promote and support high standards throughout the post-authorisation research process based on robust methodologies, transparency and scientific independence. RESULTS: ENCePP provides a point of access to researchers for industry, academia and regulatory authorities seeking collaboration for the conduct of post-authorisation studies. As of 30 November 2011, the network consisted of 98 research centres, 13 networks and 18 data sources, mostly academic and publicly funded institutions but also data source providers and contract research organisations with expertise in the conduct of post-authorisation studies. All are listed in the free, public and fully searchable electronic Database of Research Resources. A guide and a checklist on methodological standards have been published; the concept of an 'ENCePP study', including a Code of Conduct, introduced; and an electronic register of studies have been launched. CONCLUSION: It is envisaged that application of the ENCePP study concept will result in an increase in trust in post-authorisation studies of medicines. The register of studies will allow for ready access to study protocols and results, thereby enhancing transparency and facilitating review. Through the network, standards, transparency and clarity of relationships, ENCePP is expected to add to the European Union capacity to conduct robust post-authorisation studies, thereby benefiting public health. Copyright © 2012 John Wiley & Sons, Ltd.

わが国の市販後の安全性監視の現状と今後のあるべき姿

Current pharmacovigilance activities may be captured by two important concepts, pharmacovigilance planning (PVP) and risk minimization action plan (risk MAP). PVP was advocated in E2E guideline of International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) in 2004. Risk MAP was proposed in 2005 in FDA's guidance as well as in EU risk management plan (EU-RMP). PVP requires a scientific approach where important safety issues unique to each product are specified and the conduct of the study with a design best for the specified problems. Similarly, risk MAP requires developing the best strategy to mitigate the specified problems. In Japan, drug use investigation (DUI) (shi-yo-sei-seki-cho-sa) was developed as early as in 1970s and became mandatory after the re-examination system for newly approved drugs was introduced in 1979. DUI is a stereotyped survey without control group where thousands of patients prescribed a new drug are followed typically for 3 to 6 months. Within 2012 risk management plan guidance will be implemented in Japan. This may promote a better practice of risk MAP. On the other hand, the real implementation of PVP is challenging because it requires various resources which do not currently exist in Japan. For example, it is important to establish the education system which can produce people who is capable of planning and conducting a good study. In addition, the system to achieve transparency, independence and standard like European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) may be established.

The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance: application to diabetes and vascular disease

The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) is an initiative led by the European Medicines Agency (EMA) aimed at further strengthening the post-authorisation monitoring of medicinal products in Europe by facilitating the undertaking of multi-centre, independent, studies focusing on safety and on benefit/risk. A key objective of ENCePP is to provide a unique point of access for all involved stakeholders, including industry or regulatory authorities, who are seeking collaboration for the commissioning or the performance of post-authorisation studies. The 2010 EMA regulatory action relating to rosiglitazone included a pharmacoepidemiological drug utilisation study to evaluate the benefit–risk profile in a real-life setting and has also led to the commissioning of an ENCePP study to evaluate the impact of risk-minimisation activities. ENCePP seeks to improve the European Union capacity to conduct such studies and thus support decision making. Application of the ENCePP study concept will result in an increase in trust in medicines and their use. In addition, the ENCePP register of studies will serve as a resource to allow for ready access to study protocols and results, thereby ensuring transparency.