April 2009 - Uppsala Monitoring Centre

DIRECTOR’S MESSAGENo one method can be relied upon for global signal detection, and I am often surprised that theUMC is regarded as only interested in individual case safety reports (ICSRs).It is true that WHO had the first international database of ICSRs in 1968, and this was taken overoperationally by the UMC a decade later through an Agreement between WHO and the SwedishGovernment. We, at about the same time as Stephen Evans in the UK, were the first to publishdata-mining of ICSRs as an adjunct to clinical review.In the past, however, I have worked with the world’s first cohort event monitoring (CEM) system,and was instrumental in bringing the technique for use in the WHO Programme and UMC incollaboration with my colleague David Coulter. It is a natural tool for pharmacovigilance in publichealth programme roll-outs where there are cohorts of patients using new medicinal products.Now, the UMC is the first group to introduce data-mining in longitudinal patient health care records.We have been doing this for over 5 years, and finding signals successfully 1 . We use and promote each ofthese methods since they each have their strengths and weaknesses for signal detection and analysis.Ralph EdwardsDirectorthe Uppsala MonitoringCentreIndividual case safety reports have considerable value in bringing in the observations and intelligenceof those who use medicines in their daily lives. They may contain information about medicationerrors, drug and food interactions, and other special risk situations that might not be captured anyother way. They can also give, through verbatim descriptions of the adverse reaction, a subjectivedimension to the impact of the adverse reaction on that individual patient: we should try togain more of such insights. They bring the health professional and consumer reporters, and theirconcerns, directly into the process of regulating the medicines they use. Responses to their reportsalso allows for individual useful, educational feedback to them. The weaknesses are: biases, nodenominator data and differential under-reporting.Cohort event monitoring allows for a different capture of events which may or may not bemedication related. As such, unusual clinical events may be found to have a relationship tomedication, which might not be obvious to the users and reporters. These signals may be seen bythe remote observer evaluating collated cases, quantified in a continuous known cohort of exposedindividuals. Contemporaneous cohorts of other medications may provide some kind of control, butthe lack of specially selected controls is a drawback in both determining causality and attributablerisk. Coding strategies may obscure outcomes, as they may with ICSR.Longitudinal health care records allow the comparison of cohorts of exposed patients withthemselves as controls when they were not exposed (before treatment particularly) and againstall or a selected control population taken from all other patients. Data-mining techniques can beused to follow exposed patients chronologically with comparison to any type of outcome (bad,good; laboratory finding, clinical event) and to signal disproportional relationships, compared withcontrols, quickly. Patterns of multiple data elements can also be valuable in the further analysisof a signal, and for determining special risk groups. The impact of coding strategies and multipletesting, which may increase the chance of spurious findings, is a subject of further work.1. Norén, G.N., Bate, A.,Hopstadius, J., Star, K., andEdwards, I. R. Temporalpattern discovery for trendsand transient effects: itsapplication to patient records.in ACM SIGKDD internationalConference on KnowledgeDiscovery and Data Mining.2008. Las Vegas, Nevada,USA: KDD ‘08. ACM.2. Bradford Hill, A., Theenvironment and disease:association or causation?Proc R Soc Med, 1965. 85: p.295-300.So, the UMC has pioneered work in data-mining in several, different, large sets of data to increasethe richness of our knowledge, but we always acknowledge the necessity of clinical review anddiagnostic insight, as well as more specific epidemiological testing as the tools for definitive testingof hypotheses, along the lines of the Bradford-Hill criteria 2 . If you still think we just look at tens ofthousands of ICSR per quarter think again and check our website too: www.who-umc.org !2 UR45 April 2009 www.who-umc.org

contents2 Director’s Message4-5 WHO Programme news6-7 CEM – new tools in action8 Open access in the Netherlands9 Reporting statistics10-11 Genetic prediction of ADRs12-13 News from Around the World14-15 Conference reports16 Polish media in Uppsala17-19 News from Around the World20 New publications21 & 22 News from Bredgränd23 Courses and conferences24 the UMC teamThe Uppsala Monitoring Centre (the UMC) is the fieldnameof the WHO Collaborating Centre for InternationalDrug Monitoring, responsible for the management of theWHO Programme for International Drug Monitoring.An independent centre of scientific excellence, the UMCoffers products and services, derived from the WHOdatabase of Adverse Drug Reactions (ADRs) reported frommember countries of the WHO Programme.With an independent and global perspective on drugsafety, the UMC provides resources for regulatory agencies,health professionals, researchers and the pharmaceuticalindustry.The UMC’s important worldwide work is financed solelyby the organisation itself, without support from WHO,the Swedish Government, member countries of the WHOProgramme or any grant-making body.5RabatThe 2009 Annual Meeting of the WHOProgramme for International DrugMonitoring will take place in Rabat,Morocco on 2-5 November 2009.6CEM in AfricaCohort event monitoring is gettingestablished – and a new tool is helping inTanzania.9Reporting statisticsAn update on progress at the UMC inreceiving ISCRs from member countries.Communications informationVisiting address:the Uppsala Monitoring CentreBredgränd 7SE-753 20 UppsalaSwedenMail AddressBox 1051SE-751 40 UppsalaSwedenTelephone: +46 18 65 60 60Fax: +46 18 65 60 88E-mail:General enquiries: info@who-umc.orgPersonal e-mail messages may be sent to any memberof the team by putting their name (e.g ralph.edwards)in place of infoSales & marketing enquiries: info@umc-products.comInternet: www.who-umc.orgUppsala Reports © the Uppsala Monitoring Centre 200916Journalists in UppsalaA hundred Polish journalists increasedtheir knowledge of pharmacovigilancewith a visit to Uppsala last October.Editors: Sten Olsson and Geoffrey BowringISSN 1651-9779Uppsala Reports 45 www.who-umc.org 3

At a glance CemFlowCemFlow is a web-based software designed to manage all datacollection and analysis aspects of a Cohort Event Monitoring(CEM) programme. The software is based on the UMC’s tool forthe collection, reporting and analysis of ADR case reports –VigiFlow – which is used by many National Centres in theWHO Programme.The CemFlow system has been designed to be simple and userfriendly – but with flexibility to allow for simultaneous monitoringof different medicines as well as groups of medicines.CemFlow is built to manage:• Multiple CEM programmes simultaneously with easyadministration• Entry of all necessary CEM data in a ‘CEM report’• Simple registration and management of data entryusersfeedback from three pilot sites• a public health facility: Mnazi Mmoja Health Centre• a private hospital: Tumaini Hospital• a referral hospital: Muhimbili Hospitalwas encouraging and useful in fine-tuning the CEM tools.The UMC IT team is engaged in developing a data management toolCemFlow for CEM; this tool, when ready, will support the ongoingCEM initiatives in Tanzania and Nigeria.In addition to providing important safety information, CEM of ACTswill provide an opportunity to test this method in Africa. TFDA isclearly well-placed to lead the current CEM efforts in eastern Africa.The agency is aiming to complete its ACT-CEM cohort by the end ofthe year.CemFlow also provide:• Compatibility with available paper questionnaires• Search and analysis tools• Built-in dictionaries and terminologiesCemFlow will be available on the web for countries that wouldlike to carry out CEM programmes. The first version, built incollaboration between the UMC and the WHO, is alreadyavailable but will be fine-tuned as the CEM pilots in Tanzaniaand Nigeria proceed.For details about the Cohort Event Monitoring methodology,please read the WHO publication A practical handbook on thepharmacovigilance of antimalarial medicines.active surveillance method that is essentially an observation of anew medicine in the early post-marketing phase, but can also beused for older medicines.CEM trainingIn June 2007, WHO organized a CEM training course for three Africancountries: Ghana, Nigeria and Tanzania. The countries will use CEMto collect comprehensive and near-complete data that will addressthe special needs of the malaria programme, including effects ofmalaria treatment in pregnancy, specific toxicities, safety in children.Advantages over spontaneous reporting will include the ability toproduce rates, the ability to produce a near-complete profile of theadverse event and/or adverse reaction for the medicines of interest,and the possibility to identify signals at an early stage.Field visit to TanzaniaBoth Tanzania and Nigeria are now well on their way to implementingCEM for the safety monitoring of ACTs in selected health facilities intheir countries. During a recent field visit to Dar es Salaam, WHO HQPharmacovigilance Technical Officer Shanthi Pal and UMC softwarearchitect Magnus Wallberg joined the Tanzania Food and DrugsAuthority TFDA in the pilot phase of CEM implementation. PreliminaryUppsala Reports 45 www.who-umc.org 7

ACCESS TO DATATransparency of an ADR database:risk or benefit?Kees van Grootheest Netherlands Pharmacovigilance Centre LarebSince 2004 all Dutch ADRreports have been accessible atthe website of the NetherlandsPharmacovigilance Centre Lareb.Our opinion, in concordancewith the policy of the NetherlandsMedicines Evaluation Board, isthat information about thesafety of medicines should betransparent and publiclyaccessible.Confidentiality about informationregarding the safety ofdrugs suggests there is somethingto be hidden and is counterproductiveto the much-neededconfidence in pharmacotherapy.The only acceptable exception isKees van Grootheest the need for protection of theprivacy of individual patientsand (to a lesser extent) reporters. Patent-related information could be anexception, but this matter is not relevant in a discussion about theopenness of ADR databases.Experiences in the NetherlandsBefore Lareb decided on complete transparency and publish theLareb ADR database on its website, the matter was extensivelydiscussed internally, especially in the Scientific Advisory Board. Allkinds of considerations were taken into account. The currentexperiences with some main points from the discussion, are:WorkloadContrary to our expectations there was no increase in calls forinformation or other major disturbances in our normal routines.MisuseThe fear of misuse by journalists or lawyers has been shown to beunfounded. Only on one occasion did a journalist phone us about ahigh number of fatal outcomes with a certain drug. This appeared tobe an error in the way of showing the results, which suggested thefatal outcomes were related to the drug. The case involved was anexample of confounding by indication and the patient’s death was aconsequence of the serious disease for which the drug was given. Asa result, we adapted the way of presenting the outcome in order toprevent misinterpretation.PrivacyAt our website www.lareb.nl no date of birth is provided, but ageonly is given, in periods of five years and no feedback information tothe reporter can be seen. The privacy aspects were checked by anexpert lawyer in this field to ensure compliance with legislation. Wehave never received any complaints regarding this.Positive outcomesIn contrast to our concerns before implementing openness on ourwebsite, transparency resulted in some important positive side effects.Impact on clinical practiceThe final goal of all pharmacovigilance activities is to make the useof drugs safer. Besides retrieving new knowledge from daily drug use,we want to support the work of physicians and pharmacists in theirdaily practice. Many practitioners use the database in their medicaland pharmaceutical work as a source of information.The first articles have been published in papers such as the NederlandsTijdschrift voor Geneeskunde, the main Dutch medical journal, andthe British Medical Journal, in which information from our websiteis used and recognized.International exchange of informationWe were happy to discover that our web-based database is used bycolleagues in many countries. They compare their reports andpossible signals with reports and other information from theNetherlands, which is very encouraging for us.Use in unexpected waysSince our database is easily accessible, it is used by some others thanthose we had intended it for. The first new group of users was Larebemployees. It is an easy way to find information quickly, not only thereports, but also additional information such as publications, signalsand so on. The database is also used by students in medicine,pharmacy and pharmacology - and many others, including patientsand patient organizations.Publications and research by othersIf the Lareb ADR database is used by others for publications andscientific research, Lareb expects to be involved; this is mentioned inthe caveat at the website. Although the information is public, wewant to be recognized as the source. Lareb is often invited toparticipate in research and publications.ConclusionsMaking the Dutch medicines safety information available on theinternet has, overall, been a constructive development. Transparency- not only the facts, but more: the attitude - is very much appreciated.Politicians, the general public and colleagues want us to betransparent. The Dutch experience has so far demonstrated that theside effects are positive; the benefit definitely outweighs the risk. Itcontributes to earning public confidence both in a well-establisheddrug safety system and in the use of drugs itself.8 UR45 April 2009 www.who-umc.org

GENETIC PREDICTION OF ADRSEUDRAGENEEuropean collaboration to establish a case-control DNA collection forstudying the genetic basis of adverse drug reactionsCo-ordinators: Dr Mariam Molokhia, Professor Paul McKeigueLondon School of Hygiene and Tropical Medicine, University of LondonWe are currently undertaking aEuropean study called EUDRAGENE(www.eudragene.org) to establisha freely-shared case-controlcollection of DNA samples as aresource for studying genetic predictors of adverse drug reactions.Identifying genetic variants that influence susceptibility to adversereactions will advance understanding of the molecular basis of theseevents and may also lead to the development of tests that can predictindividual susceptibility to adverse reactions, with obvious benefitsto human health.Type B reactionsType B adverse drug reactions (ADRs) are often serious, limit theusefulness of drugs that are otherwise effective, and increase therisks of drug development because they lead to withdrawal of drugsafter the costs of bringing them to market have been incurred.Identifying genetic variants that influence susceptibility to ADRs hasobvious practical and scientific value. Research in this area ishampered by the lack of a resource in which to study geneticdeterminants of susceptibility to Type B ADRs. As serious Type BADRs are rare, case-control designs are the only feasible approach.A multicentre European collaboration has been necessary, as nosingle country will generate enough cases of any given ADR within areasonable time.Six centre collaborationWe are aiming to establish this freely-shared resource consisting ofclinical data and DNA samples from at least 400 cases of each class ofADR, together with a control group. We are currently collecting casesfrom seven classes of ADR that are important and easily identified,throughout six European countries; in Italy, France, Netherlands, Spain,Sweden and the United Kingdom. These ADRs of interest are; druginduced liver injury, statin-induced myopathy and rhabdomyolysis,Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), longQT syndrome, agranulocytosis, fluoroquinolone-induced tendonrupture, and mefloquine-induced neuropsychiatric reactions.local site and shipped to a laboratory at Erasmus Medical Centre inRotterdam, for extraction of DNA for further studies.Genome wide association studies of drug induced hepatotoxicity arecurrently underway with support from the Serious Adverse EventsConsortium (collaboration of academia and industry) and ColumbiaUniversity, New York as part of an international collaboration.View of London School of Hygiene and Tropical MedicineIf you would like further information about the EUDRAGENE studyplease contact Mariam Molokhia: mariam.molokhia@lshtm.ac.uk ortelephone +44 (0)20 7927 2633.Data sourcesIn each participating country suspected cases are ascertainedthrough physicians’ reports of suspected ADRs to the national orregional pharmacovigilance agency. This has been supplementedwhere necessary with case ascertainment from existing registries ofdisorders such as blood dyscrasias, from databases of drug utilizationand morbidity in primary care, and from hospital admission records.Suspected cases are invited to take part via their physicians.Additional clinical data is obtained from questionnaires and medicalrecords, before establishing whether each suspected case meets thecase definition for that class of ADR. A blood sample is taken at the10 UR45 April 2009 www.who-umc.org

HIV/AIDSPharmacovigilance for ARVs pilot projectImproving patient safety, patient care and treatment outcomes forpeople living with HIV/AIDS treatmentDr Micheline Diepart, Medical Officer, Department of HIV/AIDS, WHOReaders may recall the WHO/UNAIDS ‘3 by 5’ initiative, launched in2003 to provide antiretroviral medicines for 3 million people sufferingfrom AIDS by 2005. This target was only reached by end of 2007, butthis was seen as a major success, considering the challenges andthat most of the people on treatment are from resource-limitedcountries. This initiative has not yet been matched by the same effortto improve pharmacovigilance for antiretroviral medicines (ARVs) inlow- and middle-income settings.The background to monitoringToday, close to 4 million people worldwide have access to antiretroviralmedicines, and the new target is ‘Universal access to treatment forall’. The effectiveness of treatment programmes, particularly inresource-limited countries, risks being compromised by problemsrelated to toxicity, intolerance and drug–drug interactions. Adverseevents linked to antiretroviral medicines used in AIDS infection,whether acute or chronic, mild or severe are relatively common,affecting both individual patients and public health. They not onlyreduce the treatment efficacy with increased morbidity and mortality,but also become a public health issue, as treatment programmeeffectiveness may be reduced through increased risk of emergenceof secondary drug resistance. In spite of this, they remain onlyintermittently identified and scarcely systematically reported in lowandmiddle-income settings. New adverse events and toxicities areidentified, and antiretroviral therapy became a chronic infectiousdisease, life-long treatment, with built-in toxicities. The availabilityof numerous new drugs and drug combinations makes it critical tosystematically monitor adverse events linked to antiretroviralmedicines.The need for dataAntiretroviral medicines and other drug interactions are receivingincreasing attention too. For instance, many patients receiving ARTin low- and middle-income countries are also being treated fortuberculosis (TB) or malaria. Increasingly questions are raisedconcerning the acute and cumulative toxic effects, and impact onARV efficacy resulting from drug regimes that combine treatmentfor HIV and TB. Limited data have been collected on co-administrationof ARVs and second-line anti-TB treatment, and on artemisinincombination therapies for malaria. The influence of co-morbidity(especially hepatitis) and metabolic conditions on drug toxicity anddrug–drug interactions also needs to be better understood.Different setting, different approachMoreover, what we know of adverse events and toxicities inantiretroviral drugs is provided by pharmacovigilance and cohortevent monitoring data from developed countries. These data do notnecessarily apply to the low- and middle-income settings, where themetabolic, nutritional, genetic background may differ. In thesesettings, through a public health approach, treatments are based onstandard population-based HIVDR monitoring and surveillance,focusing on increased adherence, with a limited number ofprequalified medicines, generic products and simple recommendationsfor when to start, substitute or switch medicines due to toxicity.WHO strategyThe WHO Department of Essential Medicines and PharmaceuticalPolicies has published a document on pharmacovigilance for ARVsand organized country training in different parts of the world butthere is a need for more effort in pharmacovigilance. A joint project,initiated by the HIV and EMP Departments, funded by the Bill andMelinda Gates Foundation will develop in four directions. Firstly,harmonizing norms and definitions, tools and methodologies forimproving pharmacovigilance for ARVs as a preliminary step towardsbetter management of available information. The UMC is fully andactively involved in the development of these tools and morespecifically in developing CemFlow, an online tool for recordingadverse events observed in a cohort of patients treated with one ormore medicines. Secondly, a few countries have been selected andwill be supported to field test and implement the tools developed.The objective is to propose a model that could later be adapted andadopted in other countries, if possible integrating active and passivesurveillance methods, with training included. Thirdly, to meet theimmediate needs for critical information on adverse events andtoxicities in resource-limited settings and to better inform WHO andnational guidelines, policies and strategies, key studies will beundertaken, based on a research agenda for the three years of theproject. A project advisory group has been established and Dr MarieLindquist, UMC, has accepted to be part of it. This Advisory Groupwill, over the lifespan of the project, help WHO define, plan andguide the project’s scientific agenda, and more specifically, thetargeted studies. A first meeting in March has defined the first year’sresearch agenda. While focusing on low-income settings, it wasagreed that the project will include and refer to the very significantexisting and potential work undertaken by international cohortcollaborators to rapidly bring some response to urgent questionsregarding patient safety. Research protocols will be offered forcompetitive bidding.Collaboration in prospectThe project team will ensure the appropriate co-ordination of theproject activities and accurate reporting of data analysis and promotea wide sharing and dissemination of tools developed and datacollected. This project attracts much interest within WHO and frompartners, implementers in countries, researchers, academicians. Asfor most activities linked to pharmacovigilance, the expectation isthat it will further strengthen the collaboration between the WHO,the project partners, and the UMC.12 UR45 April 2009 www.who-umc.org

NEWS FROM AROUND THE WORLDUganda training assignmentSten Olsson and Helena WilmarSet-upPharmacovigilance in Uganda began in 2004 with the establishmentof the National Pharmacovigilance Centre (NPC) at the NationalDrug Authority (NDA). In June 2007 the NPC became a full memberof the WHO Programme for International Drug Monitoring, and sincethen Regional Centres (RCs) have been created within seven referralhospitals. Around 300 individual case safety reports (ICSRs) havebeen received through spontaneous reporting since the start of theprogramme (VigiFlow TM software is used).The practical VigiFlow training in KampalaActivitiesA training course took place in February with UMC participation,opened by Mr Apollo Muheirwe, NDA Chief Executive Officer. Thecourse members were 32 professionals from the seven regionalcentres. As well as lectures, working groups discussed causalityassessment and its application to case scenarios, and practicalsessions took place on VigiSearch TM and VigiFlow. After the course,on 20 February, the NPC was formally inaugurated with speeches byDirector General of the Ministry of Health, and the Chairman and theChief Executive Officer of the NDA, recorded by the media.MasakaOn 23 February 2009 Sten Olsson was taken by Helen Ndagije andAngela Bonabana of the NPC to the referral hospital in Masaka (oneof the Regional Centres), 2½ hours by road south of the capitalKampala. Discussions focused on the wish of the hospital to developfurther its pharmacovigilance activities, and the value the hospitalmanagement attach to quality of care. A visit was made to the HIV/AIDS clinic. While acknowledging the importance of thepharmacovigilance activity, the clinician in charge found it difficult tofind time to report adverse reactions to ARV treatment (the clinic seesaround 250 patients per day). At the health service of the District ofMasaka, the responsible officer for the healthcare system wassupportive of the pharmacovigilance system and wished to set anambitious fixed monthly target of ICSRs coming from his district.ConclusionsAs a result of the course and site visits the UMC and NDC staff haveassessed the current challenges to effective pharmacovigilance inUganda. In spite of being relatively young, the Ugandapharmacovigilance programme has a good degree of institutionaland structural stability and contains many of the key elements forachieving efficient monitoring of patient safety issues. Althoughinfrastructure, resources and time for clinicians are – as in manycountries – a key problem, there are certain steps that could be takento build on the excellent foundations which Ugandan staff havemade. These include legislation, better communications and furthereffort to involve public health programmes and professional medicaland pharmaceutical councils.Dr Sam Zaramba (Director General of the Ministry of Health), Dr FrankMwesigye (Chairman, NDA) and Mr Apollo Muhairwe (Chief ExecutiveOfficer, NDA) at the launch of the national centre.Back row: Mrs Helen Byomire Ndagije (Head of NPC), Mr Babiiha Julius,Christine Naluswata, Ms Huldah Nassali, Mr Sten OlssonFront row: Ms Angela Bonabana, Mrs Helena Wilmar, Ms VictoriaNambasa Bukenya and Dr Jeanne MuhindoWith further support on many levels the Ugandan system could movetowards reliable outcomes in terms of drug safety signals and supportfor decision-making for the benefit of patient safety at all levels ofthe Uganda healthcare system.Uppsala Reports 45 www.who-umc.org 13

conference reportsPhilippinespharmacist trainingCynthia DizaThe Philippines Bureau of Food and Drugs, in collaboration with theBureau of Health Facilities of the Department of Health, conducteda basic pharmacovigilance training course from February 17-20,2009 in the city of Davao, in the heart of the Philippines’ exoticsouth, the south-eastern portion of Mindanao Island. The objectiveof the course was to strengthen pharmacists’ clinical skills andcompetence in the recognition, prevention and management ofadverse drug reactions.The training was modelled on the WHO pharmacovigilance courseheld in Manila last September (see UR43 p7-8). The 28 participants,mostly pharmacists from government hospitals, participated activelyin discussions after each lecture: the basics of pharmacovigilance,ADR reporting, causality assessment, ADR types and management,medication errors, drug interactions, food-drug interactions;literature sources and pharmacoepidemiological methods. A statusreport from the Philippines National Centre was also presented.Singapore safetysafariAndrew BateIn December I was an invited speaker at a major DIA meeting ‘Safetyis Global: Contemporary Pharmacovigilance and Medical ProductRisk Management Strategies’ in Singapore. It was an interestingmeeting particularly with high-profile and influential presentersfrom Asia and elsewhere – such as Chan Cheng Leng and WimonSuwankesawong, Heads of the pharmacovigilance units at theSingaporean Health Sciences Authority and the Thailand Food andDrug Administration, respectively. John McEwen from Australia,Stephen A. Goldman from the USA and Elliott Brown from the UKalso spoke. Registered delegates attended from throughout the Pan-Pacific region and gave the meeting an exciting international feel. Itwas particularly interesting to hear how pharmacovigilance varies –as it needs to – between different countries, while equally reinforcingmany common global themes, such as the need for emphasis oneffective communication.One issue which arose during the course and which influences howreporting is perceived by health workers is litigation. BFAD gaveparticipants an assurance that all reports are treated with utmostconfidentiality and it would be a rare case if information is divulged,and then only if there is a real threat to public safety.The trainers comprised Dr Kenneth Hartigan-Go, Dr Suzette H Lazo,Dr Klara Tisocki (EU consultant for BFAD), Dr Douglas Ball, and DrCynthia Diza, the ADR Unit Co-ordinator.At the end of the course, the participants had a planning workshopon what they intend to do to promote and strengthenpharmacovigilance in their hospitals and to develop and instil a‘safety and reporting culture’ among health staff. The training coursewas rated well and there are plans to conduct three zonal trainingcourses to cover all government hospitals nationwide this April, Julyand August.Chan Cheng Leng and Andrew Bate (seated) with staff from theSingapore national centre.I was also invited to present a lecture at the Singapore HealthSciences Authority (HSA) where I talked about signal detection inthe context of the WHO Programme.A social high point of the visit was the trip to the ‘night safari’, aunique Singapore experience where one wanders along paths withanimals kept in enclosures at large. The sight and sound of hyenashowling as they contemplated me as a midnight feast will live longin the memory!Kenneth Hartigan-Go talking to participants in Davao14 UR45 April 2009 www.who-umc.org

DRUG SAFETY AND THE MEDIAMore education – more safetyWojciech KwileckiThe Association ‘Journalists for Health’, embracing around 100leading Polish healthcare journalists, had the privilege of visiting theUppsala Monitoring Centre during the seminar “Polka w Europie2008”.The Association was founded in 2003 to promote science-basedhealthcare standards among journalists. It quickly became thebiggest organisation of its kind in Poland - and probably in centralEurope – with 90 active members and 32 associates. These make upa group of most of the professional healthcare press, radio and TVspecialists in Poland. Prominent among the activities of theAssociation – conferences, seminars and workshops – is the annualprofessional cruise of 100 participants to Scandinavian countries,named ‘Polka w Europie’ (‘Polish Women in Europe’ – due to theAssociation’s overwhelming female membership, where outnumberedmen have to stay in the shadow).agency held a series of conferences within the ‘Safe Medicine’campaign from 2006-2008 covering the safety of antibacterialmedicines usage, safe medicine – facts and myths, safety ofpainkillers, soporific and sedative medicines and much more. Duringthe campaign the Uppsala Monitoring Centre was frequentlymentioned; so the trip to Sweden without meeting UMCrepresentatives would have been incomplete.Taking a break from the WHO Programme meeting also being heldthat week, Bruce Hugman, the UMC Communications Consultant,gave us great insight into UMC statutory duties, the history of drugmonitoring and many current issues. The interesting moment waswhen Mr Hugman raised the question: why Poland, one of the oldestWHO members having a population of 38 million, reported only3,124 reports over 36 years, while Sweden, with 9 million inhabitants,reported about 100,000 reports? The answer is not straightforward.The Chairwoman of the Polish Pharmaceutical Chamber Mrs IrenaRej suggested that the duty of reporting was implemented only afew years ago. Moreover, the Polish reporting form might be seen astoo complicated. It is very interesting that you regard the significantobstacles as mainly bureaucratic. If we want the drug monitoringsystem to function well, we need to keep the reporting simple, briefand elegant, declared Mr Hugman.The meeting had a direct impact in the Polish media. DziennikWielkopolski, the main daily paper in Poznań , capital of westernPoland, published an interview by Anna Nowak with Polish physicistAnna Jabłecka, where, challenged with the data discussed during theUppsala meeting, the doctor widely referred to UMC experiences andindicated that the reporting system in Poland should improve.Bruce Hugman addresses the large group of Polish journalists.This unique cruise came about because a ferry is the only means oftransport which allows lectures, conferences and presentations totake place while on the move. Over the 5-day ‘Polka w Europie’seminar the participants, media from all around the country,politicians, doctors, pharmacists, industry representatives, have theopportunity to receive a huge dose of knowledge. Around 20 lectures(from 9am until 6pm, with a 2-hour break) touch the living healthcareexperiences in nearby states across-the-sea: Sweden, Norway,Denmark, Finland, Estonia and Latvia. The perfect organization isthanks to a top-notch PR and event agency from Warsaw, whichmanages the herculean effort of handling around 100 participants atsea and abroad.Once disembarked, the group follow a tight schedule, meeting theirlocal counterparts, foreign officials, and prominent representativesof medicine and science. In 2008 the seminar’s motto was ‘Safety ofdrug usage - security for families’, which is why the visit to Uppsalawas of such importance.The UMC is well-known among pharmacy-oriented journalists thanksto the Polish medicinal products and medical devices agency. TheIn Gdansk the issues were covered by Jolanta Gromadzka-Andzelewicztwice: in main local daily Dziennik Bałtycki and the local online portalnaszemiasto.pl. ´ The article referred to the withdrawal of particulardrugs in Europe thanks to UMC’s work. Mr Bruce Hugman was alsoquoted as a spokesman and UMC activities were briefly described.The event was also covered in Gazeta Farmaceutyczna – Polish oldestmonthly for pharmacists, by the author of the current article. Idedicated a large part of the “Polka w Europie” general report todescribing Mr Hugman’s lecture and also quoted the abovementioneddiscussion with Mrs Irena Rej.The Uppsala meeting was one of the most interesting of almost 20various lectures held during the seminar and resulted in significantfeedback. The growth of awareness among journalists is obvious andwill result in many future publications.The visit also had a personal touch. As the group was struck by somemysterious and nasty stomach illness (ferry sea-food cuisinesuspected), the UMC crew provided our group with soothing mintlozenges. This sealed the memory of our Uppsala experience for themembers of our Association.16 UR45 April 2009 www.who-umc.org

New WHO centreUtrecht’s Collaborating Centrefor pharmacoepidemiologyAukje Mantel and Hubert LeufkensIn 2008, the Division of Pharmacoepidemiology and Pharmacotherapyof the UIPS Institute for Drug Innovation, Utrecht University, in theNetherlands, was designated as a WHO Collaborating Centre forPharmacoepidemiology and Pharmaceutical Policy Analysis. Forseveral years the Division has been collaborating with the WHODepartment of Essential Medicines and Pharmaceutical Policy onprojects related to pharmaceutical policy and innovation. The Divisionwas previously involved in the preparation of the Priority Medicinesfor Europe and the World report (2004), commissioned by the DutchPresidency of the European Union, and the evaluation of the role ofdrugs for rare diseases on the WHO Model List of Essential Medicines.From 2006 and onward the Division has started, together with WHORichard Laing, Hans Hogerzeil and Hubert Leufkens.staff members (e.g. Dr Richard Laing and colleagues), to develop aplatform for young, multidisciplinary researchers and policy analystsin order to build an innovative, independent and scholarlypharmaceutical policy community of fellows, PhD students andsenior people in the field. As part of this, the model of ‘professionalPhDs’ has been developed, in order to assist people who have dailyresponsibilities in various pharmaceutical roles to integrate theirhands-on experience with scientific research.The Collaborating Centre is aiming to translate its established recordin pharmacoepidemiological research, and the expertise of theDivision, into solving a number of public health questions. There arethree important challenges in delivering medicines to the patientswho need them. Firstly, there is a growing disconnection betweenthe new knowledge and technologies that science creates and whatis actually delivered to patients in the form of innovative andaccessible medicines that are rationally used. Secondly, thesuboptimal regulatory environment has been identified as a reasonfor the existence of therapeutic gaps and as a potentially importantbarrier to drug innovation. Thirdly, the apparent inequity in access tomedicines is still the defining characteristic of the globalpharmaceutical market place; hundreds of millions of people do nothave access to essential medicines. This work on drug development,regulatory science and access to medicines has important overlapswith drug safety, an area where the division has close links with theUMC.More information on the WHO Collaborating Centre forPharmacoepidemiology and Pharmaceutical Policy Analysis and itsactivities may be obtained from the Centre’s website(www.pharmaceuticalpolicy.nl)or the Divisional homepage (www.pharm.uu.nl/epithera).Uppsala Reports 45 www.who-umc.org 17

NEWS FROM AROUND THE WORLDAdvising WHOSten OlssonThe WHO Advisory Committee on Safety of Medicinal Products(ACSoMP) held its sixth meeting in Geneva from 4-6 March 2009.This committee provides advice to WHO and the WHO CollaboratingCentre in Uppsala on pharmacovigilance policy and issues related tosafety and effectiveness of medicines. The 6 th annual meeting waschaired by Gerald Dal Pan from the FDA, USA. He guided thecommittee through a busy agenda including issues of scientific,strategic and technical importance. Several discussion items hadbeen referred to ACSoMP by the annual meeting of nationalpharmacovigilance centres held in Uppsala in October 2008.Indicators and database accessOne such item was indicators for bench-marking and outcomeassessment in pharmacovigilance. A sub-group was assigned tocontinue developing a set of practical indicators to be considered bymember countries. After an initial discussion ACSoMP appointedanother sub-group to develop suggestions for a long term strategyfor the WHO pharmacovigilance programme. This group will submitits draft recommendations to the meeting of national centres inRabat, November 2009. Also the issue of wider access to caseinformation in Vigibase had been referred from a working group atthe latest national centres’ meeting. ACSoMP recommended WHO tofurther expand access according to defined criteria.INSMPCFour persons representing the International Network of SafeMedication Practice Centres (INSMPC), Michael Cohen, DavidCousins, David U and Annemarie Hellebek, were invited for adiscussion about the scope for wider collaboration between theglobal pharmacovigilance network and INSMPC. It was concludedthat the two networks have many common concerns and aims andthat it would be appropriate for INSMPC to be invited to the 2009annual meeting of national pharmacovigilance centres.The internetA technical issue of great importance for provision of healthinformation but also for pharmacovigilance is the availability ofbroadband internet services in low-income countries. A presentationwas given regarding Africa Health Infoway (www.who.int/africahealthinfoway), a strategic partnership with WHO involvementthat aims at supplying 53 African countries with high-capacitytelecommunications over five years. ACSoMP requested that VigiFlowbe offered as a key service through this infrastructure.UK patientreporting upThe United Kingdom’s Medicines and Healthcare products RegulatoryAgency (MHRA) has announced success both in its patient reportingas part of its long-standing Yellow Card scheme, as well as in thefirst year of a new on-line reporting form.In the past year more than 2,500 Yellow Cards were submitted bypatients or carers bringing the total number of patient reports toalmost 9,000 (since February 2008 2,500 were received). During2008, 89% of the patient Yellow Cards were from the patientsthemselves, 6% from a parent, and 5% from a carer. The Agency hasalso seen double the number of reports submitted on-line.The main trends which have emerged from in the past year were a 17per cent increase overall for all Yellow Card reports to 25,000;including an increase of 50 per cent of reporting from the public.Essential MedicinesACSoMP had received a request from the WHO Expert Committee onthe use of Essential Medicines for criteria to be employed whenassessing the safety of medicines proposed for inclusion in the WHOModel List of Essential Medicines. Recommendations were providedon the basis of very thorough background work carried out byACSoMP member Jürgen Beckman.WHO programmesRepresentatives of many of WHO’s disease programmes werepresenting updates on the progress of introduction of newpharmaceutical treatments and their safety monitoring in countries.Special attention was given to the fact that UMC now has a specialist,Jerry Labadie, devoted to safety follow-up of newly pre-qualifiedvaccines. He was on his first introductory visit to WHO headquartersduring the ACSoMP meeting and attended some of the sessions.18 UR45 April 2009 www.who-umc.org

Boost for pharmacovigilance in AfricaAlex DodooPharmacovigilance in Africa has received what is potentially a hugeboost with the imminent implementation of two projects that aregeared to provide badly-needed financial and technical support. Theseare the INDEPTH Network Effectiveness and Safety Studies (INESS),funded by the Bill and Melinda Gates Foundation, and the AffordableMedicines for Malaria (AMFm) programme, funded by the Global Fundagainst AIDS, Tuberculosis and Malaria (The Global Fund).INESSThe INESS platform, with funding of about US$26 million, plans toexamine the real-life safety and effectiveness of artemisinincombinationtherapies (ACTs) deployed for the treatment ofuncomplicated malaria in three African countries – Ghana, Tanzaniaand Mozambique. At a Protocol Development Workshop in Dar esSalaam, the INESS platform agreed to provide funding to strengthenthe existing spontaneous reporting systems as well as support cohortevent monitoring (CEM) studies in each of these countries. INESS hasagreed to provide funding to recruit a dedicated local Safety Officerin each of the 9 Districts where the studies will take place and hasalso provided funds for the activities of dedicated local safety teamswho will examine safety reports, carry out investigations and conductcausality assessment. INESS plans to innovate in the safety studiesby utilizing PDAs (hand-held computers) to collect safety informationand identifying patients for follow-up using a GPS system that showswhere recent recipients of antimalarials live. The INESS project willbe complimented by the setting-up of a large linked database to pickup safety signals. The pharmacovigilance aspects will be coordinatedby Professor David Schellenberg of the London School of Hygieneand Tropical Medicine and Dr Alex Dodoo of the University of GhanaMedical School.AMFmArtemisinin-combination therapies (ACTs) are the most effectiveremedies for treating uncomplicated malaria. They involve the use ofan artemisinin derivative and another antimalarial and this usuallyresults in cure rates over 95% when appropriately taken. However,ACTs are expensive, a quality-assured ACT costing about US$8 in theprivate sector, compared to US$0.10 for the previously-used, butnow parasite-resistant, chloroquine. The need to provide affordablegood quality ACTs for malaria patients is a key global aim in a bid toeliminate and eventually eradicate malaria. The Global Fund and itspartners therefore decided to create the AMFm to provide affordableACTs to all who need them at a cost of about US$0.10. These ACTsare intended to be widely available in all settings and the expectationis that they will be supplied as over-the-counter products, just likemost medicines for the treatment of uncomplicated malaria.Safety implicationsThe widespread availability of quality-assured and affordable ACTsraises several safety issues. These include safety when used withoutdirect medical supervision, and safety when supplied by lower levelhealth care personnel. A dynamic and relevant pharmacovigilancesystem has therefore been suggested as one of the key requirementsfor the AMFm programme and funding is being set aside for this. Toprepare countries participating in the AMFm to present a harmonizedand robust pharmacovigilance proposal, the World HealthOrganization (GMP, QSM) and the Medicines for Malaria Ventureorganized a 3-day workshop from 6th-8th April in Geneva,Switzerland. The workshop was attended by pharmacovigilanceexperts from over eight countries including Ghana, Nigeria, Senegal,Mozambique, South Africa, Kenya and Madagascar. The UnitedStates Pharmacopoeia, the Uppsala Monitoring Centre (UMC), theWHO Regional Office for Africa and two pharmaceutical companies(Novartis, Sanofi) also took part.Participants agreed that the specific objectives of anypharmacovigilance system would be to monitor the risk of ADRsassociated with ACTs made available through the AMFm programmeand supplied by the public and private sectors. This should beunderpinned by a communication and feedback strategy based onthe information generated through the pharmacovigilance system.Various approaches were agreed to achieve the pharmacovigilanceaims, including:1. traditional spontaneous reporting2. strategies to stimulate spontaneous reporting particularly amongprivate accredited retailers who are likely to dispense ACTs withinthe context of AMFm3. active monitoring of a cohort of patients exposed to ACTs (cohortevent monitoring)4. development of a pregnancy register to document birth outcomesfollowing exposure to ACTs whether inadvertent or deliberate.Boost for safetyThe INESS and AMFm programmes will surely provide large amountsof data on antimalarials in Africa and will provide benefits extendingbeyond safety monitoring of antimalarials alone. Both programmesintend to collaborate actively with the UMC and will utilize bothVigiFlow and CEMFlow to manage any safety data collected. Theactivities being planned are being led and co-ordinated by thevarious national drug regulatory authorities to ensure that thefindings of the various studies are utilized for decision making.Pharmacovigilance in Africa has received a huge boost and it ishoped that the resources provided will provide stability andsustainability for safety monitoring in Africa.Participants at the AMFm pharmacovigilance meeting in GenevaUppsala Reports 45 www.who-umc.org 19

PUBLICATIONSDrugs and BugsAnna Celén and Bruce HugmanWe are keen to hear from readers about similar well-producedpublications around the world. Equally, if you have any thoughtsabout the needs of children in your country for this kind ofinformation, do get in touch. We would like comments and adviceabout adapting content and illustrations for different cultures. Pleasecontact Bruce Hugman (mail@brucehugman.net) or GeoffreyBowring (geoffrey.bowring@who-umc.org) if you have any ideas.Vision forhealthcarecommunicationA fabulous book for children about medicines became available inSweden last November. It is a creative approach to the demanding taskof informing children about medicines and disease. In Sweden thereis no equivalent to the book, and it is a great contribution to a child’sbookshelf as well as a useful tool for health professionals treatingchildren. The target group for the book is 6-11 year olds which addsthe bonus that parents and teachers will learn something as well whilereading to their children. The book is written by Fredrik Brounéus, apharmacist and author, employed at the Swedish Medical ProductsAgency which sponsored the publishing by Edition Andersson AB.Healthcare Communication, by UMC’s communications consultant,Bruce Hugman, is published this April by the Pharmaceutical Press,London.It’s a 300-page study of the knowledge and skills needed for everyaspect of healthcare relationships and communications, withpatients firmly leading the list of priorities. The book argues that onlyin relationships of truly reciprocal partnership with patients canhealthcare achieve its potential for the safest and most effectivetherapy.The book is primarily targeted at nurses, pharmacists and doctors intraining and in practice, but it also addresses other medicalprofessions and non-medical members of the whole team, includingpolicy-makers, managers - and porters and cleaners, among manyothers. The book’s vision is of a coherent, integrated system ofhealthcare in which effective communications play a central andcrucial part in treatment of all kinds, in management of people andsystems, and in all relationships and contact with patients and thoseclose to them.The 40-page book consists of the history of medicines from ancientEgypt until today, different ways of drug administration and the pathof a drug through the body, including mechanism of action, metabolismand excretion. Other issues raised are reasons for illness and how thebody can be protected from pathogens like virus, bacteria, fungus andparasites. It also deals with the immune system, fever and vaccines,and rounds off with drug development and the future. The attractivedesign of the book is due to rich and amusing illustrations by NinaErixon-Lindroth, who has a PhD in clinical neuroscience.The title is ‘Piller och Baciller - en liten bok om läkemedel’ – inEnglish: ‘Drugs and Bugs - a little book about medicines’. The bookcould also be adapted to different countries; the UMC communicationsconsultant, Bruce Hugman, has met the author to discuss thepossibility of an English version. Many of you will share the beliefthat education of children is among the measures needed to improvepatient safety in the long-term. Fredrik Brouneus’ book is a greatexample of what can be done in providing important, basicinformation about medicines and disease for children in an attractiveand accessible way.20 UR45 April 2009 www.who-umc.org

visitorsADR reportson childrenCatrine Pansegrau HaugeAs a 4 th year pharmacy student at the University of Bergen inNorway, I am finishing my degree by writing a thesis on ADRreports on children in Norway. The thesis was prompted by thenew EU regulation on medicinal products in paediatrics whichhas increased the focus on pharmacovigilance of drugs used bychildren. I have extracted all ADR reports for a 10-year period onchildren from the Norwegian ADR database (NADRD). Based onthe analysis of the data one expects to be able to detect an effectof regulatory changes and of a national campaign in 2009focusing on ADRs in children. My inclusion criteria were:• Patients ≤ 17 years• ADRs caused by one or more drug(s), not by in utero exposureor through breast-feeding• One or more suspected drug(s) or drug related product(s),except vaccines.The thesis is carried out at RELIS in Bergen, a regional druginformation and pharmacovigilance centre (one of five regionalcentres in Norway). RELIS registers all ADR reports from its regioninto NADRD, in addition to assessing them and giving eachreporter individual feedback. The centre also helps with questionsconcerning drugs and ADRs, interactions, and offers lectures.I felt a visit to the UMCwould be quite helpful in mywriting, and a programmewas arranged to provide mewith basic information onthe function of the UMC andthe services it offers. My visitincluded presentations ofthe WHO Programme,VigiBase and WHO-ART. Ialso got a demonstration onhow to use VigiMine, whichto me is an extraordinaryprogram. It was anCatrine Pansegrau Hauge interesting and informativeday which has helped me tobetter understand how extensive the field of pharmacovigilanceis and the degree to which the UMC contributes in making drugssafer.My visit at the UMC will without a doubt help me in writing mythesis and I am very thankful for the chance to come, especiallyto Anna Celén for making the day possible.Welcome back DavidWe were pleased to see David Coulter again in March. Hecontinues to provide expert advice and input for several areas ofUMC work, especially terminology for Cohort Event Monitoringand the CemFlow system being developed.Among the topics on the crowded contents pages you’ll find:• What is effective communication?• Why do we communicate?• Vision and communication at the heart of healthcare• Core concepts and skills (caring, helping, empathy, listening,questioning, explaining and lots more)• Communication and cultural diversity• Angry and aggressive patients; mental disorders• The whole team and the whole patient• When time and resources are limited• Informed consent• Sex and sexuality• Dying and death• Effective written and spoken communications• Media relations, managing meetings and teachingAnd, especially for readers of Uppsala Reports, there are chapters onpatient safety and risk communication, with references topharmacovigilance and the WHO Programme.The text is enhanced with amusing illustrations and a large numberof provocative and illuminating quotations from familiar and obscurepersonalities.The author runs a blog and a forum to involve readers in thediscussion and development of best practice and to share experiencesand ideas.The book is available from the Pharmaceutical Press (www.pharmpress.com), Amazon and major booksellers at £29.95. Theauthor’s blog and forum are at www.BruceHugman.com.Book receivedThe Guide to Vigilance and Adverse Event Reporting, 2nd Edition2008-09. Published by Washington Information Source Co, themassive book is a compilation of the latest regulations, guidancedocuments and compliance manuals from the US FDA, the EuropeanUnion and ICH. www.fdainfo.com.Uppsala Reports 45 www.who-umc.org 21

NEWS FROM BREDGRäNDWelcome to SaraSara Bergh has recently joined the UMC,working as a Sales Assistant. This involvesensuring our commercial customers –particularly of the WHO Drug Dictionary –have their transactions administered in anefficient and timely manner.Sara is originally from Säffle in the west ofSweden. She came to work at the UMChaving studied international marketing andsales at Folkuniversitetet in Uppsala.Outside of work she is interested in sport: “In 1997 I moved toUppsala to play volleyball in Sweden’s highest league. After 6 years Inow play in the second league for Tierp Volley, more for fun, where Iam also the team captain.”Drug Safety bulletinsand the UMCAt present at the UMC we have an incomplete view of the existenceand coverage of bulletins issued by national pharmacovigilancecentres. In UR42 we requested information from nationalpharmacovigilance centres and academic departments aboutnewsletters in both print and digital format, and have managed tofill some gaps. Many thanks to those centres who responded to ourappeal!WHO-ART–MedDRAbridge updatedA bridge between WHO-ART and MedDRA was developed in 2007 forthose who want to continue using WHO-ART and at the same timeneed to be able to report ICSRs to organizations in MedDRA codedformat.The file mapping WHO-ART terms to corresponding MedDRA terms isupdated annually and the latest version mapping terms from the firstversion of WHO-ART 2009 (2009.01) to MedDRA 12.0 has now beenreleased.The bridge consists of all WHO-ART Preferred terms, not Includedterms, with a link to the nearest MedDRA term, which may be a Lowlevel term or a Preferred term. The bridge is available free of chargeto all WHO-ART and MedDRA customers.It is recommended that centres produce ADR newsletters andbulletins as a good way of sharing important information. Newslettershowever vary greatly in frequency and content and the groups atwhich they are aimed. Some regulatory authorities andpharmacovigilance centres maintain websites at which you cansubscribe to updates.The UMC is keen to see examples of good practice – in each region,in different languages and from national (or regional) centres ondifferent scales. We circulate and store recent issues for referenceand for educational purposes. We believe there may also be apossibility of future co-ordination with those responsible as editorsof pharmacovigilance bulletins.Member countries are encouraged to provide the UMC withinformation about their medicine safety newsletters where available.If the UMC is not already receiving your newsletter, do send us acopy – whether printed (to our post address), distributed by e-mailand/or downloadable from your website (to info@who-umc.org).22 UR45 April 2009 www.who-umc.org

COURSES & CONFERENCESdatestitleplaceORGANISER/CONTACT13-14 May 2009Compliance in pharmacovigilance and the role ofthe EU QPPVLondon, UKDSRUTel: +44 (0)23 8040 8621E-mail: jan.phillips@dsru.org ; www.dsru.org/13-15 May 2009Practical Guide for Pharmacovigilance: ClinicalTrials and Post MarketingLondon, UKDIA European Branch OfficeTel: +41 61 225 51 51; Fax: +41 61 225 51 52E-mail: diaeurope@diaeurope.org18 May 2009An essential guide to pharmacovigilanceLondon, UKManagement Forum LtdTel: +44 (0)1483 730071 Fax: +44 (0)1483 730008www.management-forum.co.uk1-3 June 200918th Annual Scientific Congress ARCS; Educationin PracticeSydney, AustraliaARCS Australia LtdTel: +61 (02) 8905 0829E-mail asc@arcs.com.au ; www.arcs.com.au3-4 June 2009Periodic Safety Update Reports (PSURs)Southampton, UKDSRUTel: +44 (0)23 8040 8621E-mail: jan.phillips@dsru.org ; www.dsru.org/4-5 June 2009IX Jornadas de Farmacovigilancia, 25thAnniversary of the Spanish PharmacovigilanceSystemOviedo, SpainSpanish Medicines Agency in collaboration with RegionalHealth Authority of Asturiaswww.farmacovigilancia2009.es15-17 June 2009Pharmacovigilance: A Basic Training Course forthose working on drug safety monitoring in theEU, USA and JapanLondon, UKManagement Forum LtdTel: +44 (0)1483 730071 Fax: +44 (0)1483 730008www.management-forum.co.uk24-25 June 20095th Biennial Signal Detection meeting(Pre-Conference tutorial: 23 June 2009)Southampton, UKDSRUTel: +44 (0)23 8040 8621E-mail: jan.phillips@dsru.org ; www.dsru.org/8-10 July 2009Medical Aspects of Adverse Drug ReactionsSouthampton, UKDSRUTel: +44 (0)23 8040 8621E-mail: jan.phillips@dsru.org ; www.dsru.org/12-15 July 20099th Congress of the EACPTEdinburgh, ScotlandEuropean Association for Clinical Pharmacology andTherapeutics (EACPT)www.eacpt2009.org/15-16 July 2009Introduction to pharmacoepidemiologySouthampton, UKDSRUTel: +44 (0)23 8040 8621E-mail: jan.phillips@dsru.org ; www.dsru.org/4-8 August 200910th Commonwealth Pharmacists AssociationConferenceAccra, GhanaCPA Accra 2009:E-mail: info@psgh.orgwww.psgh.org/cpa16-19 August 200925th Anniversary International Conference onPharmacoepidemiology& Therapeutic Risk ManagementProvidence, RhodeIsland, USAISPEwww.pharmacoepi.org/meetings/25thconf/index.cfmE-mail: ISPE@paimgmt.com9-10 September 2009Back to basics in pharmacovigilanceSouthampton, UKDSRUTel: +44 (0)23 8040 8621E-mail: jan.phillips@dsru.org ; www.dsru.org/23-24 September 2009Critical appraisal of medical and scientific papersSouthampton, UKDSRUTel: +44 (0)23 8040 8621E-mail: jan.phillips@dsru.org ; www.dsru.org/6-9 October 2009Annual Meeting of the International Society ofPharmacovigilance (ISoP)Reims, FranceISoPwww.isoponline.org/upcoming-meeting.html12-16 October 2009Excellence in Pharmacovigilance: Clinical Trialsand Post MarketingBerlin, GermanyDIA EuropeTel. +41 61 225 51 51diaeurope@diaeurope.orgUppsala Reports 45 www.who-umc.org 23

the Uppsala TeamDirectorRalph Edwards, MB, ChB, FRCP (Lond), FRACP Professor in Medicine, DirectorDeputy DirectorMarie Lindquist, Dr Med Sc Chief Scientific OfficerFinance and Core ServicesBirgitta Toreheim, CA Manager, Chief Financial OfficerAli Bahceci Network TechnicianBritt Gustavsson-McCurdy Corporate SecretaryAnneli Lennartsson Economy AssistantMaja Östling Administration Assistant (on study leave)Anette Sahlin Administration SupportSafety Support and ServicesMonica Plöen, BSc Pharm ManagerJenny Bate, BSc Pharm Signal DetectionCecilia Biriell, MSc Pharm Senior Specialist, WHO-ARTMohamed Farah, Pharm D Senior Specialist, Traditional MedicinesRichard Hill, BSc, MBBS Medical AssessorMalin Jakobsson, MSc Pharm WHO Drug Dictionaries Content ManagementJeanette Johansson, BA, BSc Pharm Review Panel Co-ordinatorHelena Sköld, MSc Pharm Signal DetectionElki Sollenbring, MSc Pharm WHO Drug Dictionaries Traditional MedicinesLovisa Sällstedt, MSc Pharm Safety ReportingAnders Viklund, MSc Pharm Information RetrievalHelena Wilmar, Pharmacist Team Leader, Safety ReportingMalin Zaar, Pharmacist Team Leader, WHO Drug Dictionaries Content ManagementMarketingAnnika Wallström, MSc Pharm Chief Marketing OfficerJessica Avasol Sales and Marketing AssistantSara Bergh Sales AssistantHannah Björn Marketing AssistantKatarina Hansson Senior Sales and Marketing AssistantCarl Huddénius, MSc Pharm Assistant Product ManagerAnna Mattsson, BSc Pharm Support ExecutiveMats Persson, BA Head of Sales and MarketingHenrik Sahl, Sales Support ManagerDaniel von Sydow, MSc Pharm Product ManagerExternal AffairsSten Olsson, MSc Pharm Manager, Chief WHO Programme OfficerGeoffrey Bowring, BA External Affairs Co-ordinatorAnna Celén, MSc Pharm External Affairs PharmacistJerry Labadie MD Vaccine Safety SpecialistResearchAndrew Bate, MA (Oxon), PhD Manager (on parental leave)Ola Caster, MSc Drug Safety AnalystJohan Hopstadius, MSc Eng Phys Research EngineerNiklas Norén, MSc Eng Phys, PhD Senior StatisticianKristina Star, RN, BMedSc Drug Safety AnalystJohanna Strandell, MSc Pharm Drug Safety Analyst (on parental leave)Production, Development & QualityJohanna Eriksson ManagerBill Dagérus Senior Systems DeveloperShalini George Tharakan Systems DeveloperStefan Lewenfalk Systems DeveloperAnnica Lundström, BSc Pharm Quality Co-ordinatorNike Meder, Pharmacist Production LeaderBjörn Moberg Systems DeveloperJessica Nilsson, BSc Pharm Team Leader: ICSR databaseBo Östling Senior Systems DeveloperSven Purbe, BA Senior SpecialistUlrika Rydberg, BSc Biol, PhLic Quality Co-ordinatorThomas Vidinghoff, MSc Senior Systems DeveloperMagnus Wallberg, MSc Eng Phys Senior Systems ArchitectWant a personal copy?If you do not receive a copy of Uppsala Reports directly, butwould like your own personal copy, please send your name,position, organisation, full postal address and e-mail/phoneto the UMC address below.Prefer to get the electronic version?If you would like to receive the pdf version of UppsalaReports every quarter, please let us know your details andthe e-mail to which we should send it. Uppsala Reports mayalso be downloaded from the UMC website.theUPPSALAMONITORINGCENTREMail address:Box 1051SE-751 40 UppsalaSwedenVisiting address only:Bredgränd 7UppsalaSwedenTelephone: +46 18 65 60 60Fax: +46 18 65 60 88E-mail:(general enquiries) info@who-umc.org(sales & marketing enquiries) info@umc-products.com(Drug Dictionary enquires) drugdictionary@umc-products.comInternet: www.who-umc.orgUppsala Reports ISSN 1651-9779