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Isah A.O.,University of Benin | Pal S.N.,WHO | Olsson S.,Collaborating Center for International Drug Monitoring | Dodoo A.,University of Ghana | Bencheikh R.S.,Moroccan Poison and Pharmacovigilance Center
Therapeutic Advances in Drug Safety | Year: 2012

The thalidomide tragedy in the late 1950s and early 1960s served as a wakeup call and raised questions about the safety of medicinal products. The developed countries rose to the challenge putting in place systems to ensure the safety of medicines. However, this was not the case for low-resource settings because of prevailing factors inherent in them. This paper reviews some of these features and the current status of pharmacovigilance in Africa. The health systems in most of the 54 countries of Africa are essentially weak, lacking in basic infrastructure, personnel, equipment and facilities. The recent mass deployment of medicines to address diseases of public health significance in Africa poses additional challenges to the health system with notable safety concerns. Other safety issues of note include substandard and counterfeit medicines, medication errors and quality of medicinal products. The first national pharmacovigilance centres established in Africa with membership of the World Health Organization (WHO) international drug monitoring programme were in Morocco and South Africa in 1992. Of the 104 full member countries in the programme, there are now 24 African countries with a further nine countries as associate members. The pharmacovigilance systems operational in African countries are based essentially on spontaneous reporting facilitated by the introduction of the new tool Vigiflow. The individual case safety reports committed to the WHO global database (Vigibase) attest to the growth of pharmacovigilance in Africa with the number of reports rising from 2695 in 2000 to over 25,000 in 2010. There is need to engage the various identified challenges of the weak pharmacovigilance systems in the African setting and to focus efforts on how to provide resources, infrastructure and expertise. Raising the level of awareness among healthcare providers, developing training curricula for healthcare professionals, provisions for paediatric and geriatric pharmacovigilance, engaging the pharmaceutical industries as well as those for herbal remedies are of primary concern. © SAGE Publications 2011.


PubMed | University of Zürich, Charles University and Collaborating Center for International Drug Monitoring
Type: Journal Article | Journal: Drug safety | Year: 2016

Herbal medicines are used worldwide and with an increasing popularity in Western countries. Although often perceived as naturally safe, herbals may cause severe adverse drug reactions (ADRs), with immediate allergic reactions being particularly life threatening.The aim of this study was to analyse immediate allergy-like ADRs to herbals documented in VigiBase, the WHO international pharmacovigilance database.The documentation of all suspected ADRs in association with herbal exposure reported to VigiBase from 1969 to August 2014 was retrieved. Among all reports in which WHO-ART reaction terms were indicative of acute allergic reactions, those classified as suspect with a documented causality assessment and latency time of 1 day were selected. For the most frequent specific herbal-ADR combinations, the information component (IC) as a measure of disproportionality based on Bayesian statistics was calculated.We identified 757 reports out of 1039 ADRs. Products with mixed herbals (36.0 %) as well as those administered orally (63.2 %) were predominant. The most frequent reactions were urticaria and rash (49.2 %). Anaphylactic reactions accounted for 9.5 %. Disproportionally frequent reporting of mouth edema (IC = 1.81) and anaphylactic reactions (IC = 1.24) to Phleum pretense were noted.Our findings indicate that herbal medicines for oral use carry a risk of causing immediate allergy-like ADRs. Studies using the Vigibase database can identify specific combinations of particular herbs and adverse reactions. Healthcare professionals and patients should be aware of these risks and report any serious adverse experiences.


Kuemmerle A.,Swiss Tropical and Public Health Institute | Kuemmerle A.,University of Basel | Kuemmerle A.,CRP Sante | Dodoo A.N.O.,University of Ghana | And 5 more authors.
Malaria Journal | Year: 2011

Background: In spite of enhanced control efforts, malaria remains a major public health problem causing close to a million deaths annually. With support from several donors, large amounts of artemisinin-based combination therapy (ACT) are being deployed in endemic countries raising safety concerns as little is known about the use of ACT in several of the settings where they are deployed. This project was undertaken to profile the provenance of the pharmacovigilance reporting of all anti-malarials, including ACT to the WHO adverse drug reaction (ADR) database (Vigibase) over the past 40 years. Methods. The WHO Programme for International Drug Monitoring, the Uppsala Monitoring Centre (UMC) provided anonymized extracts of Vigibase covering the period 1968-2008. All countries in the programme were clustered according to their malaria control phase and income status. The number of individual case safety reports (ICSRs) of anti-malarials was analyzed according to those clusters. Results: From 1968 to 2008, 21,312 ICSRs suspecting anti-malarials were received from 64 countries. Low-income countries, that are also malaria-endemic (categorized as priority 1 countries) submitted only 1.2% of the ICSRs. Only 60 out of 21,312 ICSRs were related to ACT, 51 of which were coming from four sub-Saharan African countries. Although very few ICSRs involved artemisinin-based compounds, many of the adverse events reported were potentially serious. Conclusions: This paper illustrates the low reporting of ADRs to anti-malarials in general and ACT in particular. Most reports were submitted by non-endemic and/or high-income countries. Given the current mix of large donor funding, the insufficient information on safety of these drugs, increasing availability of ACT and artemisinin-based monotherapies in public and private sector channels, associated potential for inappropriate use and finally a pipeline of more than 10 new novel anti-malarials in various stages of development, the presence of well functioning national pharmacovigilance systems is vital to ensure safe and responsible scale up of ACT deployment. Bringing together the competencies of national pharmacovigilance centres and various types of organizations in the NGO, academic and private sectors with global coordination to create short- and long-term solutions may help address the lag between rapidly growing ACT use and poor ADR reporting. © 2011 Kuemmerle et al; licensee BioMed Central Ltd.


Pal S.N.,WHO | Olsson S.,Collaborating Center for International Drug Monitoring | Brown E.G.,Elliot Brown Consulting Ltd
Drug Safety | Year: 2015

The Monitoring Medicines project (MM), funded by the FP-7 EU framework, was carried out between 2009 and 2013 by a consortium of 11 partners. The objectives were to support and strengthen consumer reporting of adverse drug reactions (ADRs); expand the role and scope of national pharmacovigilance centres concerning medication errors; promote improved use of pharmacovigilance data; and develop methods to complement spontaneous reporting. The work was organised into four themes: patient reporting; medication errors; drug dependence, counterfeit and substandard medicines and clinical risk estimation; and active and targeted spontaneous pharmacovigilance. MM differed from some other major pharmacovigilance initiatives by having participants from developing countries in Asia and Africa and in leaning towards public health and communicable diseases. MM brought together stakeholders including WHO, drug regulators, pharmacovigilance centres, consumers, public health and disease specialists and patient safety networks. Resources and methodologies developed directly by, or with support from, MM include electronic systems/tools for consumer ADR reporting and cohort event monitoring; publication by WHO of handbooks on consumer reporting, medication errors and pharmacovigilance for TB medicines; methodologies for detecting drug dependence and substandard or counterfeit medicines in ADR databases; and a database on HIV treatment risks with a risk assessment tool. MM enabled stakeholders to achieve more than if they had worked alone in pursuit of patient safety. © 2015, The Author(s).


Olsson S.,Collaborating Center for International Drug Monitoring | Pal S.N.,World Health Organization | Dodoo A.,University of Ghana
Expert Review of Clinical Pharmacology | Year: 2015

In the past 20 years, many low- and middle-income countries have created national pharmacovigilance (PV) systems and joined the WHO's global PV network. However, very few of them have fully functional systems. Scientific evidence on the local burden of medicine-related harm and their preventability is missing. Legislation and regulatory framework as well as financial support to build sustainable PV systems are needed. Public health programs need to integrate PV to monitor new vaccines and medicines introduced through these programs. Signal analysis should focus on high-burden preventable adverse drug problems. Increased involvement of healthcare professionals from public and private sectors, pharmaceutical companies, academic institutions and the public at large is necessary to assure a safe environment for drug therapy. WHO has a major role in supporting and coordinating these developments. © 2015 Informa UK, Ltd.


PubMed | SRDC Software Research & Development and Consultancy Ltd., Advanced Clinical Applications Research Group, Middle East Technical University, Lombardia Informatica S.p.A. and Collaborating Center for International Drug Monitoring
Type: | Journal: BioMed research international | Year: 2016

Depending mostly on voluntarily sent spontaneous reports, pharmacovigilance studies are hampered by low quantity and quality of patient data. Our objective is to improve postmarket safety studies by enabling safety analysts to seamlessly access a wide range of EHR sources for collecting deidentified medical data sets of selected patient populations and tracing the reported incidents back to original EHRs. We have developed an ontological framework where EHR sources and target clinical research systems can continue using their own local data models, interfaces, and terminology systems, while structural interoperability and Semantic Interoperability are handled through rule-based reasoning on formal representations of different models and terminology systems maintained in the SALUS Semantic Resource Set. SALUS Common Information Model at the core of this set acts as the common mediator. We demonstrate the capabilities of our framework through one of the SALUS safety analysis tools, namely, the Case Series Characterization Tool, which have been deployed on top of regional EHR Data Warehouse of the Lombardy Region containing about 1 billion records from 16 million patients and validated by several pharmacovigilance researchers with real-life cases. The results confirm significant improvements in signal detection and evaluation compared to traditional methods with the missing background information.


Noren G.N.,Collaborating Center for International Drug Monitoring | Noren G.N.,University of Stockholm | Hopstadius J.,Collaborating Center for International Drug Monitoring | Bate A.,Collaborating Center for International Drug Monitoring | And 3 more authors.
Data Mining and Knowledge Discovery | Year: 2010

Large collections of electronic patient records provide a vast but still underutilised source of information on the real world use of medicines. They are maintained primarily for the purpose of patient administration, but contain a broad range of clinical information highly relevant for data analysis. While they are a standard resource for epidemiological confirmatory studies, their use in the context of exploratory data analysis is still limited. In this paper, we present a framework for open-ended pattern discovery in large patient records repositories. At the core is a graphical statistical approach to summarising and visualising the temporal association between the prescription of a drug and the occurrence of a medical event. The graphical overview contrasts the observed and expected number of occurrences of the medical event in different time periods both before and after the prescription of interest. In order to effectively screen for important temporal relationships, we introduce a new measure of temporal association, which contrasts the observed-to-expected ratio in a time period immediately after the prescription to the observed-to-expected ratio in a control period 2 years earlier. An important feature of both the observed-to-expected graph and themeasure of temporal association is a statistical shrinkage towards the null hypothesis of no association, which provides protection against highlighting spurious associations. We demonstrate the usefulness of the proposed pattern discovery methodology by a set of examples from a collection of over two million patient records in theUnitedKingdom. The identified patterns include temporal relationships between drug prescriptions and medical events suggestive of persistent and transient risks of adverse events, possible beneficial effects of drugs, periodic co-occurrence, and systematic tendencies of patients to switch from one medication to another.


Caster O.,Collaborating Center for International Drug Monitoring | Caster O.,University of Stockholm | Noren G.N.,Collaborating Center for International Drug Monitoring | Noren G.N.,University of Stockholm | And 3 more authors.
Statistical Analysis and Data Mining | Year: 2010

Most measures of interestingness for patterns of co-occurring events are based on data projections onto contingency tables for the events of primary interest. As an alternative, this article presents the first implementation of shrinkage logistic regression for large-scale pattern discovery, with an evaluation of its usefulness in real-world binary transaction data. Regression accounts for the impact of other covariates that may confound or otherwise distort associations. The application considered is international adverse drug reaction (ADR) surveillance, in which large collections of reports on suspected ADRs are screened for interesting reporting patterns worthy of clinical follow-up. Our results show that regression-based pattern discovery does offer practical advantages. Specifically it can eliminate false positives and false negatives due to other covariates. Furthermore, it identifies some established drug safety issues earlier than a measure based on contingency tables. While regression offers clear conceptual advantages, our results suggest that methods based on contingency tables will continue to play a key role in ADR surveillance, for two reasons: the failure of regression to identify some established drug safety concerns as early as the currently used measures, and the relative lack of transparency of the procedure to estimate the regression coefficients. This suggests shrinkage regression should be used in parallel to existing measures of interestingness in ADR surveillance and other large-scale pattern discovery applications. © 2010 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 3: 197-208, 2010.


Giezen T.J.,University Utrecht | Mantel-Teeuwisse A.K.,University Utrecht | Meyboom R.H.B.,University Utrecht | Meyboom R.H.B.,Collaborating Center for International Drug Monitoring | And 3 more authors.
Drug Safety | Year: 2010

Background: Biologicals have specific characteristics, as compared with the small molecule drugs, and carry specific risks. Safety problems, for example infliximab and the risk for tuberculosis, have been identified via spontaneous reports of suspected adverse drug reactions (ADRs). However, in general there is limited data on the nature of spontaneously reported suspected ADRs for biologicals. Objective: To map the safety profile of biologicals as compared with all other drugs. In addition, mechanistic classes of biologicals will be compared. Methods: Data was obtained from the ADR database (VigiBase) maintained by theWHOCollaborating Centre for International Drug Monitoring. A disproportionality analysis was performed in which case reports for biologicals and all other drugs (the reference group), reported between January 1995 and December 2008, were selected. Vaccines were not included in the analysis. Suspected ADRs were classified according to Medical Dictionary for Regulatory Activities (MedDRA®) version 12.0 at the System Organ Class (SOC) level. Biologicals were classified into mechanistic classes: antibodies, cytokines, enzymes, growth factors, hormones (reference group), interferons, receptors and others/various. The safety profile of the biologicals versus all other drugs in the database and of the various mechanistic classes of biologicals was compared using the proportional reporting ratio (PRR). Results: 191 004 case reports containing 546 474 suspected ADRs were reported for 62 different biologicals, and 2 556 209 case reports containing 8 761 522 suspected ADRs were reported for all other drugs (the reference group). It was found that two-thirds of all suspected ADRs reported for biologicals were reported for five active substances: etanercept (20.3%), interferon-b-1a (15.6%), infliximab (11.6%), teriparatide (10.7%) and adalimumab (9.0%). Comparison of the safety profile of biologicals and the reference group showed that suspected ADRs for biologicals were more frequently reported in the SOCs Infections and infestations (PRR 4.5), Surgical and medical procedures (PRR 2.4) and Neoplasms benign, malignant and unspecified (PRR 2.1), and less frequently reported in the SOCs Psychiatric disorders (PRR 0.4), Vascular disorders (PRR 0.4) and Pregnancy, puerperium and perinatal conditions (PRR 0.4). Regarding the differences in safety profile between various mechanistic classes of biologicals, compared with hormones (reference group), Infections and infestations were more frequently reported for receptors and antibodies. Neoplasms benign, malignant and unspecified were more frequently reported for antibodies, cytokines, interferons and receptors, and less frequently for enzymes as compared with the reference group. Conclusions: In VigiBase, five biologicals comprise two-thirds of the suspected ADRs reported for biologicals, which might distort the relation found between a specific biological and a specific adverse event in case of quantitative signal detection. Therefore the choice of reference group to be used in case of quantitative signal detection should be considered very carefully. This study confirmed that biologicals have a different safety profile compared with all other drugs in the database and, within the group of biologicals, differences exist between mechanistic classes. Infections are, for example, frequently reported for receptors and antibodies, which often have an immune compromising effect. Such predictable safety issues should be specifically studied by preregistration clinical trials and/or targeted pharmacovigilance. In addition, since not all adverse reactions can be predicted or detected during development, spontaneous reporting remains an important tool for the early detection of signals. © 2010 Adis Data Information BV. All rights reserved.


Olsson S.,Collaborating Center for International Drug Monitoring | Pal S.N.,World Health Organization | Stergachis A.,University of Washington | Couper M.,World Health Organization
Drug Safety | Year: 2010

Background: The WHO Programme for International Drug Monitoring aims to develop a comprehensive global pharmacovigilance strategy that responds to the healthcare needs of low-and middle-income countries. However, first there is a need to measure and understand existing conditions and pharmacovigilance initiatives intended in these settings. Very few investigations have carried out such a systematic assessment of the pharmacovigilance landscape in recent years in low-and middle-income countries. Objective: To assess current and planned pharmacovigilance activities in lowand middle-income countries, identify gaps and the most urgent pharmacovigilance priorities at national and international levels, and define the elements of a sustainable global pharmacovigilance strategy. Methods: A standardized questionnaire was sent to 114 representatives of countries participating in the WHO Programme for International Drug Monitoring (but excluding Australia, Canada, New Zealand, Switzerland and the International Conference on Harmonization countries, i.e. countries in Europe, Japan and the US) and to a few other identified contacts from non-member countries. The questionnaire was sent out between March and July 2008 and was designed to collect information on the structure, resources, functions and achievements of pharmacovigilance systems in low-and middleincome countries, with a focus on pharmacovigilance activities supported by national health authorities including public health programmes. All questionnaires that were returned by the end of July 2008 were used in the analysis. Results: Fifty-five completed questionnaires were received by July 2008, representing a response rate of 55.5%. Forty-five percent of the pharmacovigilance centres in the analysis were established during the 1990s and 49% were set up later; 69% were affiliated with their Drug Regulatory Agency, 20% with the Ministry of Health and 9% with a university or other scientific body. Few countries (23 of 55) have any budget allocated for pharmacovigilance. Public health programmes (44%), the Global Fund to fight AIDS, Tuberculosis and Malaria (36%), universities (26%), poison centres (21%), Management Sciences for Health (18%) and Rational Use of Drugs networks (15%) sponsor some pharmacovigilance activities. In addition to direct pharmacovigilance activities, many centres are also involved in other activities such as drug information (63%), promoting patient safety (52%), rational use of drugs (46%) and poison information (15%). Some countries have sentinel sites to monitor HIV/AIDS patients (in seven countries) and other special groups. Information gathered through pharmacovigilance activities is used to assist regulatory functions in most countries (n = 42), lack of training and funding were mentioned as being major challenges to pharmacovigilance in many countries. Conclusions: This study has helped identify some of the special challenges and barriers to promoting pharmacovigilance in low-and middle-income countries. A pharmacovigilance strategy in these settings needs to help build health systems that can serve the purpose of multiple health conditions. It needs to identify and implement feasible systems, governance, infrastructures, human resource, training and capacity building, sustainable methodologies and innovations in pharmacovigilance; a key component will be the dissemination of medicines safety information to policy makers and regulators and knowledge sharing with healthcare professionals through high quality informatics and learning tools, with rational use of medicines and patient safety as the ultimate goal of pharmacovigilance. © 2010 Adis Data Information BV. All rights reserved.

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