J ULY 2017 ISSUE 76

Pharmacovigilance

Our vision is a world where all patients and professionals make wise therapeutic decisions. INSPIRE. ENGAGE. TRANSFORM ISSUE 76 / UPPSALA REPORTS 1 Director´s message Contents

N THIS ERA OF ELECTRONIC COMMUNICATION, I must would be better. What is the right mix of rigour and fl exibility admit I take delight in receiving the occasional old- no doubt varies from individual to individual, from situation to fashioned letter; a neatly folded piece of paper wrapped situation, and over time; but I do think we need both to thrive. in an envelope, with a stamp and a handwritten address. In the world of today, I am concerned that we build systems IThere is something very attractive in anticipating its content and organisations where fear of failure is a stronger driver than while opening it, particularly if you know from the curiosity and open-mindedness; and I think there is 06. handwriting that the person who sent it is a good too much emphasis on short-term productivity friend. This was the case when I recently received rather than long-term real gains. We do need ANNIE & MAC good governance and work discipline to TRAVEL THE a letter from Ed Napke, a colleague and friend WORLD of many years. Ed was the inventor of the “We need achieve results. But we also need to release ingenious pigeon-hole system in Canada in to release creative creative forces for good and allow people the infancy of modern , to turn new ideas and chance fi ndings and is still active as a consultant to UMC. forces for good and into innovative solutions to the many Here is how his long and successful career allow people to turn problems we all face. This can only be 12. in pharmacovigilance started: new ideas and done by actively encouraging some level of HEALTH TECHNOLOGIES IN KENYA The World Health Organization (WHO) playfulness and -taking in working life. asked member countries to set up a chance findings I am convinced that the world would be adverse reaction monitoring program and to into innovative better for all of us if we left more space and 21. make more stricter laws on drug manufacturers room for people to sometimes veer into the UMC’S in the making of new . It was a long story solutions.” unknown, and to try new things without fear 19TH PV but Canada volunteered with 9 other countries to of being punished if they get something wrong COURSE see if we could pool the data. This is where I came or don’t achieve an immediate result. in. I was on my way to the University of California to do research on the effects of acceleration on humans and was asked to P.S. IN CASE YOU WONDER – yes, I still have a physical tray wait a year because the current researcher did not wish to return to in my offi ce for incoming post. Apart from the odd contract, South Africa and apartheid. My friend Dr J.M. offered me the job requiring my signature, it mostly fi lls up with glossy management 26. to take on the project which I agreed to. I thought it would take 2-3 magazines that I never ordered and promotional prospects REAL-TIME years, instead it became my life’s work 1963-1990. from companies trying to entice me to join their next 10. VACCINE SAFETY conference on drug development or to use their What he wrote reminded me that many life-changing SIGNAL DETECTION SURVEILLANCE decisions seem to be the result of chance events. I certainly services for our next international meeting. IN ERITREA think that the world of pharmacovigilance has benefi ted from If anyone knows where I can order a spam the chance taken by Ed Napke all those years ago. And, having fi lter for such communications, do let me 18. lived for a bit, I have learnt to appreciate and make good use of know. PATIENT opportunities that have come my way, many seemingly out of ADHERENCE the blue. It may seem as a paradox that I often argue for the benefi ts of proper work planning. I will continue to do so, but I want to make it clear that planning is just the means to achieve an end, not an end in itself. If we bury ourselves too deep in meticulous planning activities, there is a risk that wonderful new prospects may pass unnoticed. As so often, the challenge is to get the balance right; we must fi gure out in what circumstances careful UPDATES HEALTH INFORMATION OPINION: PATIENT REPORTING UMC training course in Nepal; Birth of TECHNOLOGIES IN RESOURCE- Pharmacovigilance expert Sten Olsson planning is needed, and when a more open, relaxed approach Marie Lindquist, Director 04. 12. 24. a national pharmacovigilance system in POOR SETTINGS explains the importance of patient- El Salvador. Mobile technologies are widespread derived safety reports. in Kenya. Could they help advance MEDICINES SAFETY IN INDIA healthcare? TECH UPDATE 08. Q&A with Dr Kalaiselvan, head of the 28. Drug name look-up in mobile apps; Indian Pharmacopeia Commission, on SAFETY CONCERNS WITH HPV Montenegrin pharmacists report the challenges of working in the world’s 16. digitally. UPPSALA REPORTS Covering the world of pharmacovigilance second most populous country. Novel data mining method explores signals associated with human IN BRIEF Editor-in-Chief Paula Alvarado. Editors Alexandra Hoegberg, Federica Santoro & Geoffrey Bowring. Editorial committee Supported by a team of IN FOCUS: ERITREA papillomavirus vaccine. 30. News from UMC and the world of multi disciplinary pharmacovigilance experts. Production UMC Global Communications. Design Daniel Hansson, Zellout, Sweden. 10. A home-grown signal detection strategy pharmacovigilance. Cover photo Rob Lewine, Getty Images. helps Eritrea make sense of its small SIGNAL DETECTION national ADR database. 20. UMC and Lareb join forces to identify Contact Uppsala Monitoring Centre, Box 1051, S-751 40 UPPSALA, SWEDEN | [email protected] | +46-18 65 60 60. Web www.who-umc.org signals in patient-reported ADRs. Social media UMCGlobalSafety company/Uppsala-Monitoring-Centre UppsalaMonitoringCentre c/UppsalaMonitoringCentre

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KATHMANDU increasing burden of non-communicable vision is that it [the pharmacovigilance diseases and a larger elderly population, programme] is implemented nationwide perhaps in need of multiple medicines, and that it is used even by the general issues regarding rational use of medicines public, the users of medicines,” Mr Sharing knowledge to boost the Nepalese and their interactions are arising. “In Dhakal says. “I see everything very terms of pharmacovigilance, it is very positively.” challenging now,” admits Mr Dhakal. He stresses the need for international pharmacovigilance programme support, knowledge sharing and net- AN IMPORTANT STEP towards strengthening working in the ongoing process. “This UMC staff travelled to Kathmandu last spring to train pharmacovigilance any pharmacovigilance system is to will really help us move this programme include it in the regulatory framework, a ahead,” he concludes. colleagues in Nepal. What they found was a country that, despite the challenges process which has now been initiated in it has had to face since a devastating earthquake two years ago, is determined to Nepal. The Drug Act has been revised and is now being processed at ministry level. strengthen its pharmacovigilance activities. information material on the topic, since Step by step, the system for monitoring one important piece of the puzzle is to medicines safety is improving, and the Therése Lundin Pharmacovigilance Offi cer, UMC educate both physicians and the general director general is optimistic for the N LATE APRIL, UMC staff members basic topics in pharmacovigilance, activities in the country. In recent years, [email protected] public. future. Sara-Lisa Wargert, Therése Lundin including awareness raising and effective the number of regional centres set up to Anti-microbial resistance is not the only “It is not only Nepal working in this and Gediminas Norgèla visited communication, and offered a hands-on collect reports of adverse drug reactions Gediminas Norgèla concern, there are other troublesome issues area, a lot of countries are really focusing Kathmandu, Nepal to present a training session on the VigiFlow system, increased and there are ten of them in Communications Consultant, UMC related to pharmacovigilance. With an to improve pharmacovigilance. My Itraining course in pharmacovigilance. which DDA uses as their national the country today, mainly in teaching [email protected] Course participants came from Nepal’s database for individual case safety reports. hospitals. drug regulatory authority – the The training also touched upon data Department of Drug Administration assessment and analysis, to highlight the DESPITE THE CHALLENGING times, (DDA) – and the country’s regional importance of using the collected data to the health sector has developed in the EL SALVADOR implement pharmacovigilance, leading to pharmacovigilance centres. identify safety issues and act upon them, past decade, according to Mr Narayan the opening of a new national pharmaco- Over two days, UMC staff illustrated ultimately improving . Prasad Dhakal, director general at vigilance offi ce (Centro Nacional de The course, set up in collaboration DDA. Maternal and Farmacovigilancia, CNFV). The same with the WHO Country Offi ce in Nepal, is rates are decreasing and life expectancy A pharmacovigilance system is born month new ‘Salvadoran Technical Rules for part of DDA’s recent effort to expand and is increasing. “Access to medicines and Pharmacovigilance’ were launched and with For many years, El Salvador lacked a So far, the pharmacovigilance undertaken strengthen the national pharmacovigilance health facilities has improved a lot, both national system for monitoring the safety was mostly in two public hospitals, each one that legal document the CNFV aims to fulfi l system. Nepal is still recovering from a in the private and the public sector,” says of medicines. Thanks to the guidance of following their own practices. El Salvador many critical indicators. massive earthquake that hit the country Mr Dhakal. But many challenges remain. WHO and PAHO, the country has now has had its own yellow reporting card for In March 2017 El Salvador started a in 2015 and killed 8,700 people, injured A major issue is anti-microbial resistance, begun to take a more active approach to almost three decades, but there was no two-week national pharmacovigilance nearly 22,000 and infl icted enormous which according to the director general is pharmacovigilance. The Minister of Health rigorous evaluation of the cases, and no sensitisation programme for healthcare damage to the country’s infrastructure. a widespread problem in Nepal. Staff from has committed to develop the system, to national database to collect and store reports professionals from the regulatory authority, Despite the burden this has placed on the regional centres confi rm the need protect the safety of the population when until recently. hospitals, academia and industry. The UMC national authorities, DDA has lately for urgent action in this area. DDA a drug is used. In October 2016 a law was passed to was present for one week to talk about the begun to boost pharmacovigilance is currently planning to develop WHO Programme, to promote the use of the online reporting form connected to the management tool, VigiFlow, and for other contributions to the event. It was an amazing experience to be at the launch of a national pharmacovigilance activity in a country, having been involved right from the beginning. More than 150 healthcare professionals participated with great enthusiasm during the whole training activity, in what is now the 127th member of the WHO Programme.

Elki Sollenbring Pharmacovigilance Offi cer, UMC [email protected] @ESollenbring

Lourdes Jarquin Lourdes Jarquin and Elki Sollenbring with Head, El Salvador pharmacovigilance trainees in El Salvador. Pharmacovigilance Centre [email protected]

4 UPPSALA REPORTS / ISSUE 76 INSPIRE. ENGAGE. TRANSFORM INSPIRE. ENGAGE. TRANSFORM ISSUE 76 / UPPSALA REPORTS 5 Communications Communications

NNIE AND MAC’S ADVENTURES efforts to drive behavioural change in “We tell some of the best stories to each other Young readers enjoying UMC’s comic book in & MAC – Uppsala Monitoring Centre’s relation to medicines. every day. That´s how we learn, share and build a Uganda, Armenia, Cabo Verde, Malaysia and E comic book on pharmacovigilance “Hopefully, the children will bring Jordan (clockwise from top left). I • – is currently being piloted in this new knowledge back to their homes community. Stories help us shape knowledge and Photos: Armenia, Scientifi c Center of Drug and severalA countries and the feedback and contribute to everyone´s better Medical Technology Expertise. Cabo Verde,

N remember it!” Paula Alvarado/UMC. Jordan, Jordan Food and D will be implemented in the coming number. understanding of the benefi ts and of Drug Administration. Malaysia, National Pharma-

N “We have not completed the evaluation yet, medicines”. “We tell some of the best stories to comic is planned for autumn 2017 and will

L L L ceutical Regulatory Agency. Uganda, National but the response we received so far is very The comic is the fi rst in a series aiming each other every day. That´s how we learn, explore the topic of antibiotic resistance.

Drug Authority.

A A

R positive. We know that children in different to explain medicines safety to a young share and build a community. Stories help Paula, Fredrik and Paul are now hard at

• parts of the world fi nd the magazine fun and audience. Written by Fredrik Brounéus us shape knowledge and remember it!” work to incorporate feedback from the pilot O exciting, and at the same time they learn and illustrated by Paul Crumacker, added Alvarado. countries and create new storyline and Interested? T W about medicines,” said Paula Alvarado, head the story follows Annie and her pet Children in Armenia, Cabo Verde, illustrations that are both educational and For more information, contact Paula Alvarado, R E of Global Communications at UMC. The hummingbird Mac on their heroic attempt Jordan, Malaysia and Uganda received fun - a fi ne balancing act. UMC’s head of Global Communications, on A H organisation launched Annie and Mac’s to stop evil Count Erfeit from producing the fi rst issue of the comic as part of an UMC aims to publish two comic books [email protected] VEL T Adventures as part of its communication and selling fake medicines. initial pilot phase. A second issue of the per year. Story ideas are welcome!

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OW WAS INDIA’S and raise awareness about ADR reporting district hospitals that can be set up as ADR PHARMACOVIGILANCE among the clinicians. In India, another monitoring centres. SYSTEM ESTABLISHED? challenge is that we need to empower the I’m very optimistic about the future. – Before the pharmacists – pharmacist empowerment I’m very confi dent, because everyone is Pharmacovigilance is very much required to enhance ADR supporting us – UMC’s support is there as Programme of reporting. well as WHO’s support. And everybody is India (PvPI) was on board, we have very good communication “I think effective assigned to the Indian WHO ARE THE MAIN REPORTERS OF ADRS? channels, and a very effective system. Again, communication and Pharmacopoeia Commission (IPC) in – Doctors, pharmacists, nurses and I want to stress that communication and H2011, pharmacovigilance in the country was consumers report ADRs in India. We get good partnerships and working relationships management are very carried out in a scattered manner. Once it most reports from hospitals where we’ve are very important. So, I’m 100% confi dent important for came to IPC, we started building a network set up ADR monitoring centres. We have and very optimistic that we are going to among the stakeholders, we brought all the established a system with one focal person in mature from being an emerging programme pharmacovigilance.” institutions and interested organisations each of them. Then we have our PvPI staff to an advanced one. under one umbrella, and we were able to working in every ADR monitoring centre. build a strong network of communication Through them the reports are coming from Alexandra Hoegberg doctors and nurses. with the stakeholders. Communications Offi cer, UMC I think effective communication and [email protected] management are very important for HOW DO YOU WORK WITH THE NATIONAL @alex.hoegberg pharmacovigilance. We were able to learn AND REGIONAL CENTRES? from previous programmes why they had – The national coordinating centre comes not been successful in India. It was a lack of under the Ministry of Health and Welfare, Government of India in Ghaziabad. That communication, and the proper organisation PHARMACOVIGILANCE IN INDIA was not there to coordinate the activities. is the headquarters for pharmacovigilance. India joined the WHO Programme for Under this umbrella, we have regional ADR So once the IPC assumed the responsibility International Drug Monitoring in 1997. for the PvPI, we started to invite different monitoring centres in every state in India. In 2016, 4,2% of all new suspected ADR partners and stakeholders – particularly In order to provide regular training reports submitted to WHO’s global Uppsala Monitoring Centre and WHO. to the ADR monitoring centres, we’ve database of individual case safety reports, Then gradually we started identifying more identifi ed eleven regional training centres VigiBase, were sent by India, making them regional (ADR) – including JSS Hospital in Mysore. So the sixth most active reporting country monitoring centres and were able to establish every year JSS organises at least one globally that year. quality as well as quantity of reporting. training programme for pharmacovigilance The Pharmacovigilance Programme The most successful part of this professionals in the region. Similarly, we of India was established in 2010 as the National Coordinating Centre for programme is that we’ve been able to have training centres in other parts of monitoring ADRs in the country, and connect to the government properly. We’ve the country. It means that a person from came under the Indian Pharmacopoeia IMPROVING managed to convince our government and Mysore, for example, doesn’t have to travel Commission. It falls under the Central medicines safety policymakers about the importance of to Delhi for training, they can attend the Drugs Standards Control Organisation pharmacovigilance. training at JSS. India is a big country – we (CDSCO) of the Ministry of Health & Family cannot invite everyone to Delhi for each Welfare (MOHFW). WHAT ARE THE CHALLENGES TO training. So in order to reduce expenditure PHARMACOVIGILANCE IN INDIA? and train more people we have set up these – In a country like India, there are a lot of regional training centres. challenges – particularly under-reporting. The cause of under-reporting is the work WHAT’S NEXT FOR PVPI? burden on doctors, who are over-loaded. – In India we have more than 600 districts IN INDIA They will not have the time to report. So we (which are administrative divisions of a state engage in a kind of solicited spontaneous or territory). The Drugs Controller General How do you manage national medicines safety in a country as reporting; we approach them and ask them of India, Dr G. N. Singh, is very keen on for ADR reports. expanding the programme up to district sprawling and diverse as India? Dr Kalaiselvan from the Indian Of course there is also a need to educate level and we’re planning to identify more Pharmacopoeia Commission sat down with Uppsala Reports for WHO IS DR V. KALAISELVAN? “The most successful part of this programme Dr V. Kalaiselvan (M.Pharm, Ph.D) is a Q&A on the challenges and progress in pharmacovigilance the Chief Scientifi c Offi cer at the Indian is that we’ve been able to connect to the Pharmacopoeia Commission. He is responsible for managing the Pharmaco- in the world’s second-most populous country. government properly. We’ve managed to vigilance Programme of India, and works convince our government and policymakers with different partners in pharmaco- about the importance of pharmacovigilance.” vigilance at national and international levels.

8 UPPSALA REPORTS / ISSUE 76 INSPIRE. ENGAGE. TRANSFORM INSPIRE. ENGAGE. TRANSFORM ISSUE 76 / UPPSALA REPORTS 9 In focus: Eritrea In focus: Eritrea

“Weekly case-by-case assessment is the main strategy for signal detection in Eritrea, which helps detect safety signals even based on a single .”

was only about collecting and reporting UMC’s search and analysis tool VigiLyze, of the safety signals identifi ed by the NC ADRs. There was a concern that the which allows for country-specifi c views of are new adverse drug reactions, important national pharmacovigilance programme data from WHO’s global ICSR database safety issues encountered with inappropriate wasn’t equipped to address all safety VigiBase, has also been important in use and/or administration of issues related to medicines in Eritrea. This strengthening some safety signals. and genetic variations have also been motivated the centre to run a practical signal detected by using preventability assessment. detection course from Uppsala Monitoring RITREA’S NATIONAL CENTRE Communications from the big regulators are Centre staff in the country’s capital Asmara routinely communicates with less relevant for us as they are often related in 2015. manufacturers and to new products, not available in Eritrea, Following this UMC course, the programme managers, and some of where we use old drugs for different reasons. Eritrean National Centre (NC) detected theE signals identifi ed by the centre have To minimise or prevent the identifi ed two relevant safety signals of public health motivated regulatory action, such as product risks, the NC also communicates its interest: artesunate/-induced label changes, post-authorisation safety fi ndings to the international community, extrapyramidal reactions in children and studies, inclusion of the identifi ed risk into healthcare professionals, and other young adults, and a rapid diagnostic test boxed warnings, restriction in use and partners. In addition, the NC is carrying for malaria that failed to detect malaria availability of the product, as well as the out epidemiological studies to further parasites. These signals gained much withdrawal of a product from the domestic substantiate some of the identifi ed safety attention from the international community. market. signals. In 2016-2017, six more safety signals were Previously, our regulatory decisions have Inside an old pharmacy in Asmara. detected. relied on safety communications from big Mulugeta Russom regulatory agencies, many of which are Head, Eritrean Pharmacovigilance Centre AVING A SMALL national database not relevant to our situation. Though most [email protected] of ADRs, it is impractical to look at IGNAL DETECTION IS statistical signals the way many a challenge for many high-income countries do. Instead, Home-grown pharmacovigilance offi cers, weeklyH case-by-case assessment is the main especially those working in strategy for signal detection in Eritrea, low- and middle-income which helps the NC detect safety signals signal detection countries. This was widely even based on a single case report. The Data discussed during the 2014 Processing (DPS) and Signal Management National Centres meeting in Sections (SMS) of the NC are the main Tianjin, China, where many representatives players in checking completeness of ADR sheds light on safety Sincluding myself voiced our concern at being reports and quality of case assessment unable to detect safety signals. Many approaches. The DPS ensures that countries with small national databases of individual case safety reports (ICSRs) are as issues in Eritrea reported adverse drug reactions (ADRs) and complete as possible and arranges routine a limited pharmacovigilance workforce fi nd and preventability assessment it diffi cult to detect safety signals that sessions. Once a potential safety signal is primarily concern their domestic market. identifi ed, it is the turn of the SMS to go for Since 2015, Eritrea’s National Pharmacovigilance Centre has In 2014, a public health programme further signal assessment. manager in Eritrea expressed his satisfaction Another strategy is involving physicians carried out analysis of domestic adverse drug reaction reports, in seeing pharmacovigilance fl ourish and in the case assessment process. Recently, to better understand medicines-related issues in the country, diffuse within the healthcare system, which the NC has recruited three volunteer improved the collection of reports of adverse pharmacovigilance medical offi cers to Mulugeta Russom, head of the and rely less on safety information from external sources. effects from all parts of the country. The take part in the weekly case assessment Eritrean Pharmacovigilance Centre. manager then asked if pharmacovigilance sessions and signal detection processes.

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SHORT DRIVE out On the walls surrounding the settlement, “In a country with an of Nairobi’s city informative messages on drug abuse are centre takes you to painted in colourful graffi ti. estimated population Kibera, an Although basic services are not readily of 47 million, internet HEALTH extremely poor available in Kibera, internet access is easy to community in the come by. In a country with an estimated penetration stood at outskirts of the population of 47 million, internet 90% by the end of last Kenyan capital, penetration stood at 90% by the end of last and home to year, and the total number of mobile money year, and the total INFORMATION around 250,000 accounts was around 32 million, according number of mobile people. The to the Communications Authority of Kenya. money accounts was government owns this land but does not Low-income countries have undergone a recognise the settlement. Despite its rapid development of mobile infrastructure around 32 million.” TECHNOLOGIES IN Aconsiderable size and vicinity to the capital, during the last decade. Due to the growing the 13 villages of Kibera lack even the most number of cell phone users, improved related activities, and facilitate data basic services and infrastructure, such as internet coverage, as well as the rising acquisition. They would also facilitate the running water, paved roads and healthcare. affordability of these technologies in analysis of behavioural trends in the use of Electricity is just being introduced in some resource-limited environments, health healthcare resources, thus decreasing the RESOURCE-POOR parts, and remains a problem, information technologies might just be the workload and costs to the healthcare system. with fi ve or six households sharing a way to reach formerly under-served patients. common toilet and bathroom. The expansion of mobile services might Y VISIT TO the local health clinic There is a sense of congestion upon reduce administrative challenges and replace in the Bombolulu village entering Kibera. Cars and old trucks drive some traditional interactions with the underlines the need to somehow SETTINGS on unmade, bumpy roads. People push healthcare system. Health information bolster patient access to health servicesM in Kibera. The clinic stands right in around barrels with yellow plastic containers technologies could replace the costly of fresh water for sale, vegetable stands are development of traditional healthcare the centre of the settlement, surrounded by Internet penetration and mobile phone use stand at 90% in Kenya, but scattered along the streets, and barbershops infrastructure and facilities, and offer the open sewage systems. From a health clinics in the country’s poor communities struggle to meet the basic and hairdressers take up every other shack. means to do follow-ups, monitor health- perspective, it seems paradoxical to have a needs of patients. UMC’s Afi fa Trad asks if health information technologies could support and improve primary healthcare in resource-poor countries. Photo: Getty Images.

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health facility in the midst of it all. The “Mobile technologies have the potential to clinic is a satellite of the Shining Hope for play a unique role in advancing healthcare, Communities (SHOFCO) Main Clinic, particularly in resource-limited or rural settings located in another part of Kibera. It is “The expansion of mobile privately funded and all medical staff services might reduce where communites have skipped the traditional operating there are locals. There are four development of healthcare infrastructure.” other satellite clinics, and if referral is administrative challenges needed patients are assisted with fees for and replace some traditional travel and admittance to the Kenyatta National Hospital or Mbagathi District interactions with the Hospital in Nairobi. healthcare system.” Inside the clinic’s small, poorly lit consultation room, I meet Dr Anderson Kyalo, who explains how the clinic operates. The work there appears to be mainly paper based; patient records and what seem to be prescriptions are placed on his tiny desk by a colleague during our brief discussion. Dr Kyalo is the only doctor working this day and he expects to see around 50 patients. The clinic only treats outpatients and they provide no health services at night, nor are there any emergency wards in this part of Kibera. This poses a problem, Dr Kyalo says. The clinic is open 10 hours a day during the week and 8 hours on Saturdays. His colleagues are two community workers The health clinic in Kibera´s Bombolulu village. with some medical and , who conduct follow-ups through home visits and health talks with the patients. The rest the medications they’re prescribed, and how OBILE TECHNOLOGIES HAVE the of the staff consists of a pharmacist, a nurse, access to medications and compliance to potential to play a unique role in and a laboratory technician. treatment are ensured when medicines are advancing healthcare, not in stock. particularly in resource-limited T IS EVIDENT that there are many socio- At the staff side of the pharmacy, between Mor rural settings where communities have economic and logistical challenges to the shelves in the stockroom, two chairs are skipped the traditional development of optimum health and medicines safety placed for occasional health talks and healthcare infrastructure, and leapt into in Kibera. However, if fully follow-ups with patients. Communication modern technology. To achieve maximum Iimplemented and with staff trained for about adverse effects is straightforward and impact, we need to take a fresh look at the them, electronic and mobile health systems direct, according to Mr Ojwang. Patients are opportunities and challenges lying ahead, – so-called e-Health and m-Health – could usually informed of what mild adverse and come up with innovative approaches supply the means to improve health effects might be expected with a certain tailored to the setting at hand. Sometimes management. In addition to providing type of drug. They are also made aware that we have no other choice than to walk down a user-friendly platforms for smooth they should come back to the pharmacy for bumpy road that no one has paved before us communication between healthcare further advice and dialogue before stopping – in the most literal sense. providers and patients, digital health S I REFLECT on these issues, I their treatment altogether, if they experience technologies would benefit settings like continue my visit. Only a few a side effect. In case a suspected adverse Kibera in a number of other ways. Round- minutes’ walk from the clinic stands effect becomes known to the pharmacist the-clock electronic access to medical the only registered pharmacy in this there are reporting forms available, but sources would increase the availability of Apart of Kibera, where pharmacist Jorma unfortunately they are locked away in a information at the point of care, and help Ojwang is at work. Like many healthcare cupboard in the back of the pharmacy. clinicians keep up-to-date with best workers in Kibera, Mr Ojwang is a former This is another area where health practices and treatment guidelines. resident of the area. When asked why he information technology could prove its Moreover, electronic handling of patient chooses to work here, he shrugs his value. By supplying novel health data could reduce the need for bulky paper shoulders in resignation and answers, almost management tools, mobile technology could Afifa Trad documentation, and the use of clearly as if he has no choice: “This is my people, not only boost overall health education in Specialist, legible, electronic prescriptions could help you know. I feel for them.” We discuss how Kibera but also improve patient compliance Pharmacovigilance Consulting, UMC Pharmacy in Kibera. avoid certain medical errors. the vulnerable population of Kibera afford and reporting of adverse effects. [email protected]

14 UPPSALA REPORTS / ISSUE 76 INSPIRE. ENGAGE. TRANSFORM INSPIRE. ENGAGE. TRANSFORM ISSUE 76 / UPPSALA REPORTS 15 Research Research

“New approaches to the analysis of spontaneous Current safety concerns reports may better identify the relevant case series for thorough with HPV vaccination signal evaluation.” Using cluster analysis – a novel data-driven approach to

signal exploration – UMC and the Danish pharmacovigilance centre have review of the Danish case reports revealed that they included additional terms that researched the extent of safety concerns associated with HPV . were also found in many HPV vaccine reports in VigiBase from other countries. Given the relative lack of awareness of ITH THE PUBLICATION of POTS, UMC’s researchers speculated that “Current safety concerns with traditional signal detection methodology – human papillomavirus vaccine: relying on disproportionality measures at a cluster analysis of reports in the level of single drugs and adverse event WVigiBase” in the journal Drug Safety this terms – might not fully characterise this year, UMC contributed original research to signal. The hypothesis was that different the ongoing global conversation regarding reporters might use different adverse event safety signals for the human papillomavirus (AE) terms to describe similar conditions, (HPV) vaccine. and yet there could be enough overlap Work on the topic of the HPV vaccine was between these reports to identify subgroups initiated in the spring of 2015 when UMC of HPV vaccine reports with similar AE researchers were contacted by the national profi les. A novel data-driven approach to pharmacovigilance centre of Denmark, the signal exploration, AE cluster analysis, was Danish Health and Medicines Authority used to test this hypothesis. (DHMA). UMC was asked to assist in The clustering algorithm targeted all interpreting a large local cluster of reports of HPV vaccine reports that included two or postural orthostatic tachycardia syndrome more adverse drug reaction (ADR) terms (POTS) – a dysfunction of the autonomic and had been received into VigiBase before nervous system – from a specialist clinic in January 1, 2015. It generated a total of 54 Copenhagen. A physician there had noted clusters containing at least fi ve reports. a larger-than-expected number of referrals The four largest clusters contained 71% of to the syncope clinic for young girls with a HPV reports in the analysis, and the case diverse set of symptoms, such as headache, series defi ned by these clusters described dizziness, fatigue, vision disturbances and ADRs that are included in the product abdominal pain. After undergoing various label, namely local and systemic reactions, tests of the autonomic nervous system many allergic/hypersensitivity reactions and of these girls were found to have POTS. vasovagal episodes. Four smaller clusters The DHMA requested UMC’s help to were identifi ed that contained case reports explore whether this syndrome was being relevant for consideration in assessment of reported from any other countries in the the ongoing safety concern. TRADITIONAL STATISTICAL signal detection study is that new approaches to the analysis WHO Programme for International Drug The most commonly reported AE methodology, which is based upon of spontaneous reports may better identify Monitoring. terms were headache, dizziness, fatigue, disproportionality between single drug–AE the relevant case series for thorough signal or syncope; three of these four AE terms pairs, highlights only those cases in which evaluation. POTS HAS BEEN a poorly-understood and were reported in >50% of the reports in a diagnosis of interest, such as POTS, is largely under-recognised diagnosis, as the clusters. These clusters had a higher reported. In contrast, in UMC’s analysis, Rebecca Chandler revealed in the relative paucity of published proportion of serious cases compared with reports with and without the diagnosis of Medical Doctor, UMC data regarding its pathophysiology and HPV reports overall (44-89% in the clusters POTS based upon the pattern of multiple [email protected] . Prior to 2013, there had compared with 24%). Only a minority of reported AEs, were clustered together. This @RebeccaChandle1 been only approximately 80 case reports reports in the clusters included AE terms allowed for the identifi cation of additional Chandler RE et al, “Current safety Photo: Shutterstock of POTS received into VigiBase, WHO’s of diagnoses to explain these symptoms; case reports which were relevant to further READ concerns with human papillomavirus MORE: global database of suspected adverse drug however, the majority of all cases reporting assessment of the signal. vaccine: a cluster analysis of reports reactions, for any medicinal product. A POTS were included in these clusters. One of the important messages from the in VigiBase”, Drug Safety, 2017.

16 UPPSALA REPORTS / ISSUE 7675 INSPIRE. ENGAGE. TRANSFORM INSPIRE. ENGAGE. TRANSFORM ISSUE 76 / UPPSALA REPORTS 17 Research Research

success and to avoid drug resistance. Pharmacovigilance studies, through Patient adherence as a active patient follow-up and mining of longitudinal health records, can reveal problems commonly associated with a particular condition, which can be important for the development of trust part of pharmacovigilance between healthcare providers and patients. Social and INTERVENTIONS INVOLVING pharmacists in Patient- The expanding scope of pharmacovigilance from drug safety to patient medicines management – such as economic reviews, pharmaceutical care related safety in the last decades has brought attention not only to the inherent services, developing care plans and providing follow-up – are effective in safety of medicinal products, but also to the way they are being used. empowering and motivating patients in adhering to their treatment. Clear communication about the risks that come with a certain treatment is inherent in OWADAYS, MEDICATION hospitalisation, and increased costs for pharmacovigilance in the healthcare delivery pharmacovigilance, and an open dialogue several of the factors mentioned above, and ERRORS are considered healthcare systems. It is also known that system, according to the FDA. This has led is essential to building an atmosphere of the importance of continuity of care. reportable in adverse drug reactions (ADRs) frequently to improved dialogue between prescribers, trust. Such trust allows patients to share Patient adherence issues should be pharmacovigilance result in non-adherence to medicine pharmacists and patients. information about non-adherence and the regarded as adverse drug events, and systems since they have . Other common reasons for non- reasons behind it. In this atmosphere of therefore, it is important that non- the potential of leading to adherence include the taste, form and route THERAPY-RELATED FACTORS trust, patients and healthcare professionals adherence should become part of patient harm. One of administration of medicines, their cost, Pharmacovigilance can provide evidence can learn from each other. pharmacovigilance programmes, tackling important aspect of the length of treatment, forgetfulness, on major ADRs that may occur during In Lausanne, Switzerland, a patient- this silent in the real world of polypharmacy, patients’ beliefs and the agreed therapy, how to manage centred medication adherence programme pharmacotherapy. medication errors concerns the failure of Therapy- Npatients to adhere to treatment schedules as communication breakdown between them, and when to report problems. has been established. It involves face-to-face agreed with, or prescribed by, healthcare patients and healthcare providers. related Pharmacovigilance analyses of longitudinal patient interviews by pharmacists, objective Sten Olsson professionals. A WHO review classifi es factors patient healthcare records can provide measures of the actual medication intake Sten Olsson WHO has estimated that adherence contributing to non-adherence into fi ve forecasts on the likely persistence of with daily feedback from the treatment Pharmacovigilance Consulting rates to chronic medicinal treatments dimensions, namely: social and economic; problems that have been encountered. Such team to the patient, and then processing [email protected] @StenOlssonPV is only about 50%. Non-adherence has healthcare team and system-related; therapy- information builds confi dence between the results in medication adherence been described as a silent epidemic and related; patient-related; and medical- healthcare professionals and patients. reports. Lessons learned from this activity Marie Paule Schneider is estimated to play a role in 21-37% of condition-related factors. Pharmacovigilance include the critical importance of patient Pharmacienne-cheffe adj. secteur preventable adverse drug events. Non- can contribute to our learning about these reveal important social or economic factors PATIENT-RELATED FACTORS empowerment, the need to train the recherché, Policlinique Médicale adherence can result in antimicrobial factors and infl uence them. behind non-adherence. Patients’ motivation, anxiety, forgetfulness, healthcare professionals involved to target Universitaire resistance, treatment failure, prolonged misconceptions, cultural beliefs and taboos [email protected] SOCIAL AND ECONOMIC FACTORS HEALTHCARE TEAM AND SYSTEM- can all affect adherence. Open and correct Treatment failures are often reported RELATED FACTORS information to patients about possible Delese Mimi Darko in pharmacovigilance systems, and Integrating pharmacovigilance in complications or possible ADRs associated CEO, Ghana Food and Drugs Authority [email protected] some may be due to non-adherence. In healthcare teams at all levels improves with treatment should increase patient this perspective, non-adherence can be dialogue on agreed treatments and the empowerment and motivation, and reduce their fear. seen as an adverse drug event. Active risks involved. Patients should be offered World Health Organization, “Reporting pharmacovigilance follow-up of exposed easy means to report treatment outcomes READ and learning systems for medication patients can reveal how poverty, age, gender, to the healthcare team or the national MEDICAL-CONDITION-RELATED FACTORS MORE: errors: the role of pharmacovigilance illiteracy, cultural beliefs, self-medication pharmacovigilance system. It’s not just vital to treat a diagnosis; centres”, 2014. and so on affect adherence to treatments. Patient adherence and learning understanding the challenges patients Health In Ghana, an interactive text messaging about treatment-related problems were are facing is important for the provision Condition- Thomsen LA et al, “Systematic review system- service has been introduced to allow both improved in Ghana by including of patient support as well. For example, related of the incidence and characteristics related reporting of ADRs and promote adherence; pharmacovigilance as a mandate for HIV patients are often faced with multiple of preventable adverse drug events in ambulatory care”, Annals of most messages are linked to adherence healthcare teams that managed mass-drug challenges, such as additional tuberculosis Pharmacotherapy, 2007. issues, according to the country’s Food administration against tropical diseases. or viral hepatitis illness, comorbidities due and Drugs Authority (FDA). Systematic Ghana has also introduced an indicator- to the ageing population, drug abuse and World Health Organization, reviews of social media and websites based pharmacovigilance assessment tool social stigma. Adherence to anti-retroviral “Adherence to long-term : managed by patient organisations can also for hospitals with the objective of integrating treatment is fundamental for treatment evidence for action”, 2003.

18 UPPSALA REPORTS / ISSUE 7675 INSPIRE. ENGAGE. TRANSFORM INSPIRE. ENGAGE. TRANSFORM ISSUE 7675 / UPPSALA REPORTS 19 Signal detection Education

Finding patient narratives in VigiBase UMC and the Dutch pharmacovigilance centre Lareb carried out a signal detection exercise specifi cally focusing on adverse drug reaction reports fi led by patients, identifying both new signals and new details of known ADRs.

EMBERS OF THE Research for potential signals. Over four days, the The second signal was dry eyes and department at UMC joined with teams assessed a total of 212 drug–ADR amitriptyline. A review of the product colleagues from the Netherlands combinations. As a result of this work, labelling for healthcare providers and the TH Pharmacovigilance Centre Lareb eight signals were communicated to the patient information leafl et revealed that only toM design and execute a signal detection national pharmacovigilance centres in the the term “anticholinergic effects” is included. exercise focused on adverse drug reaction WHO Programme for International Drug While healthcare providers would be likely to (ADR) reports received directly from Monitoring. understand that dry eyes are a manifestation patients. Lareb is the WHO Collaborating of such effects, a patient would probably not. Centre for Pharmacovigilance in Education TWO OF THE SIGNALS were new aspects of The signal recommends an update of the and Patient Reporting and has recognised known ADRs, which were detailed in patient information leafl et to explicitly list eye patient reporting in pharmacovigilance since narratives in the patient reports. The dryness as an . 2003; for its part UMC hoped to benefi t patients’ narratives provided important from their experience and draw on their information on the severity of the ADRs as THE EXPERIENCE WAS very valuable both as expertise to investigate if safety signals well as their impact on the patients’ quality a face-to-face collaboration with one of the relevant to patient concerns could be of life. national centres in the WHO Programme, identifi ed in VigiBase, WHO’s global The fi rst concerned genital itching and in confi rming that drug safety concerns database of suspected adverse drug reactions. and dapaglifozin. Dapaglifl ozin is of the of direct importance to patients can be The signal detection exercise was class of oral medications used to treat identifi ed in a global database such as prepared throughout the spring of 2016, type 2 diabetes, termed sodium glucose VigiBase. with discussions about how traditional cotransporter-2 inhibitors (SGLT- 2i). statistical signal detection methodologies Itching in the genital area is a common could be adjusted to prioritise drug–ADR non-serious adverse reaction for these types Rebecca Chandler Medical Doctor, UMC combinations whose case series included a of drugs, which was known at the time of [email protected] signifi cant proportion of patient reports. In approval. However, from the patient reports @RebeccaChandle1 addition to the routine review of product it was identifi ed that the itching could be information intended for healthcare so severe as to provoke discontinuation of INTERNATIONAL providers for information on the ADRs the drug. The signal highlights the fact that highlighted in the statistical screening, some events can be characterised as non- a decision was taken to also review the serious in the setting, but in patient information leafl ets, to ensure that the post-marketing period may manifest as patients are provided with adequate and severe events with a large enough PHARMACOVIGILANCE understandable information on the ADRs. impact on the patient’s quality In October 2016, a team from UMC of life that discontinuing the travelled to the town of ‘s-Hertogenbosch medication is in the Netherlands – home of Lareb – to necessary. TRAINING COURSE assess a list of drug–ADR combinations Uppsala Monitoring Centre welcomed 29 participants from 23 countries to its renowned annual pharmacovigilance course in Uppsala in May. The course offers two weeks of training focused on teaching the practical skills needed to run effective pharmacovigilance programmes.

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“The knowledge I “The course provided obtained will guide me me with pharmaco- to improve pharmaco- vigilance knowledge vigilance practices in I did not have before, my country. It will help and this will definitely me put in my best effort benefit the South to make Albania part of African public.” the big picture within the WHO PIDM, and Mafora Florah Matlala, BPharm Medicines Regulatory Authority, contribute to patient South Africa safety worldwide.”

Dajana Roshi, MSc Pharmacy Albania National Centre

“The UMC pharmaco- vigilance training course was memorable, “Fantastic, matched inspiring and well expectations! I hope the organised by a passion- knowledge gained will ate and knowledgeable be of great use to improve team. I left there the quality of pharmaco- motivated to develop vigilance practices in pharmacovigilance in Qatar.” the Caribbean region.”

Rian Marie Extavour, RPh, PhD Pallivalappila Abdul Rouf, MPharm, MSc, PhD Pharmacy Educator, Trinidad and Tobago Womens Hospital, Qatar

Photos: Gediminas Norgèla and Göran Ekeberg for UMC.

22 UPPSALA REPORTS / ISSUE 76 INSPIRE. ENGAGE. TRANSFORM INSPIRE. ENGAGE. TRANSFORM ISSUE 7675 / UPPSALA REPORTS 23 Opinion Opinion

“If we succeed in mobilising patients worldwide into active reporting, we can Patient reporting is the create even bigger and more diversifi ed databases of suspected problems future of pharmacovigilance associated with drug exposure.” Patient-derived reports add a richness to our understanding of medicine safety that would not be achieved by relying on healthcare professionals’ reports alone. Pharmacovigilance specialist Sten Olsson explains why.

BELIEVE THAT direct patient reporting showed that nurses’ or pharmacists’ identifying novel adverse reactions, but expensive or inaccessible health facilities. to seeing what the renaissance will bring. holds the key to the future of reports are just as valid, and that there is they play an important role in confi rming Direct patient reporting systems have A word of caution though. Focusing only pharmacovigilance. While we keep little overlap between them. Perhaps not previously described ones. An old medicine already been introduced in many low- and on patient reporting might make health struggling to convince healthcare surprisingly, those studies indicated that taken by a new patient is in some ways a middle-income countries. They are more professionals feel redundant, which would Iprofessionals to report, often with little members of different professional categories new medicine. A drug may have been on likely to reveal whether adverse reactions to be disastrous. If there is one thing we have response, patients are usually happy to share are more likely to report issues connected the market for several years and its adverse self-treatment have manifested and whether learnt from decades of pharmacovigilance Photo: Shutterstock.Photo: their experiences if we provide a respectful to their role. Whereas physicians mostly reactions well described, but that will not the patient adhered to the treatment or activities, it’s that there is no single truth. environment for sharing information. describe serious problems that require their stop patients from reporting – the adverse not. Information on patient adherence We will always need the observational and The reporting domain has undergone intervention, nurses highlight issues that reaction they experience will be new to is crucial to understanding treatment analytical intelligence of trained physicians, signifi cant changes since the early days of arise during patient care, and pharmacists them and if they are bothered by it, they will outcomes, but is often not shared with nurses and pharmacists to understand why pharmacovigilance. When I started working tend to report problems related to the keep on reporting. Conversely, healthcare healthcare professionals. Reasons for lack of medicines occasionally cause harm and in the fi eld, reporting was completely owned drug’s dosage or its interaction with other professionals limit themselves to reporting adherence may well be revealed in a direct how to minimise that damage. Nurses, by physicians. The common perception medicines. the most serious cases after medicines have patient reporting system, if the patient pharmacists, doctors and patients each hold was that since doctors are trained to make been on the market for a couple of years. feels reassured that confi dentiality will be a piece of the puzzle and only by placing the differential diagnoses - in other words PATIENTS, ON THE OTHER HAND, contribute Patients’ reports will better refl ect the actual maintained. pieces together will we be able to see the big to distinguish between the effects of the an additional level of information. They are burden of medicine-related problems for picture at last. Everyone - patients included disease and the effects of the medicine - they often well educated and can make valid society. IF WE SUCCEED in mobilising patients – needs to be invited to the big round table should be the only ones to report. There observations about their health status. We Involving patients in drug safety worldwide into active reporting, we can of medicine safety. was a great fear that random observations know from scientifi c studies that patients reporting has additional advantages. In create even bigger and more diversifi ed from lay people would distract and delay can teach us a lot about the impact of drug many communities and in many countries, databases of suspected problems associated the uncovering of patterns of reactions to intake on quality of life. Patients are also healthcare services and professionals are not with drug exposure. Combined with rapidly medicines, the fi rst step to identify new more likely to report events that seem easily accessible, or the costs of consulting developing technology for data storage and signals. Today, when artifi cial intelligence is questionable to physicians, nurses and them are prohibitive. Self-treatment with analysis, such collections should lead to the used to recognise patterns in big databases, pharmacists. Healthcare professionals tend pharmaceuticals or traditional remedies earlier detection and a deeper understanding Sten Olsson random observations are much less to refrain from reporting altogether if they is common in such settings and adverse of the range of effects that medicines exert Sten Olsson distracting. In the early days however, data cannot determine the cause, or possible consequences will rarely be reported in different populations. A recent article Pharmacovigilance Consulting [email protected] storage capacity was limited and it made cause, of the problem. Patients however are to healthcare professionals. Electronic referred to direct patient reporting as the @StenOlssonPV sense to only store validated reports from not inhibited by such concerns and their reporting via free messaging services or ‘renaissance of pharmacovigilance’ and I trained physicians. candour makes them valuable players in the smartphone apps allows medicine users to couldn’t agree more. We are only at the Härmark L et al, “Patient-reported safety The physicians’ reporting monopoly identifi cation of new signals. report directly to the pharmacovigilance beginning of this exciting development in READ MORE: information: a renaissance of pharmaco- was challenged in the 1990s, when studies Not only do patients contribute to centres, bypassing the need to consult medicine safety, and I am looking forward vigilance?”, Drug Safety, 2016.

24 UPPSALA REPORTS / ISSUE 76 INSPIRE. ENGAGE. TRANSFORM INSPIRE. ENGAGE. TRANSFORM ISSUE 76 / UPPSALA REPORTS 25 Research Research

ACCINE SAFETY IS in the US, and has led to the identification Delays in CPRD data can be due to extensively studied in of several safety signals, from which three either delays in making an initial diagnosis, clinical trials before a were confirmed and resulted in changes in in receiving feedback from other levels vaccine is approved. the vaccination recommendation. The three of care, or in data being made available However, there is limited signals in question were for the measles- to researchers. Data is made available to power to detect rare – but mumps-rubella-varicella combination researchers on a monthly basis, which potentially serious – vaccine and febrile seizures; the 2010/2011 enables the construction of a system that adverse drug reactions. trivalent inactivated influenza vaccine looks at data every month. Post-licensure safety surveillance is thus and febrile seizures; and the monovalent The research team has also assessed Vrequired to ensure timely detection of rotavirus vaccine and intussusception. delays caused by receiving feedback from potential safety signals. There are several other levels of care. For example, when a methods to conduct post-licensing DESPITE THE WIDESPREAD use of this type patient is diagnosed in a hospital it might monitoring, including passive and active of surveillance in the US, only a few other take time before the general practitioner forms of surveillance. countries – including New Zealand and the receives information about the diagnosis. Near real-time In 2005, the Vaccine Safety Datalink UK – have implemented near real-time The assessment measured how long it (VSD) in the US proposed a new method surveillance systems. This might be related takes for information such as diagnosis to assess safety during post-licensing to the need for readily available data from made in hospitals to be added to the CPRD vaccine safety surveillance surveillance: near real-time vaccine electronic health records, which is not data. This measurement was undertaken safety surveillance using electronic health collected or made accessible everywhere. for outcomes of particular relevance to records. Unlike other methods, near real- In the UK there are several research-level vaccine safety surveillance, i.e. outcomes time surveillance starts shortly after a electronic health records that can be used that might be interesting to evaluate as in the UK vaccine is introduced into the market and to perform near real-time vaccine safety potential adverse effects of a vaccine – such data is checked at regular intervals, for surveillance. However, this type of as Guillain–Barré syndrome, Bell’s palsy, example every week or every month. It uses surveillance has not been fully applied. optic neuritis and febrile seizures. For these A research team from the London School of Hygiene & sequential tests, based on the sequential A research team from the London School outcomes, the results indicate that most probability ratio test that was developed by of Hygiene & Tropical Medicine and Public events recorded in CPRD occur within a Tropical Medicine and Public Health England is looking the mathematician Abraham Wald in the Health England is assessing the possibility month – a delay which is compatible with 1940s and is frequently used in industry and to implement a near real-time vaccine near real-time surveillance. to implement a near real-time vaccine safety surveillance clinical trials. safety surveillance system using the Clinical Since its introduction in 2005 there have Practice Research Datalink (CPRD). CPRD BASED ON THIS RESULT, the next step is to system using electronic health records in the UK. been several methodological developments, contains clinical data available in primary evaluate whether there is enough power to statistical tests made available, knowledge care, including information on diagnosis, detect signals using CPRD. This will also regarding the properties of these tests, vaccines administered in primary care, and include exploration of the best statistical and options to account for delays in data referrals and feedback from secondary care. tests to use to assess different pairs, and the availability. There was particular interest This data is generated from information that options to account for previously identified in these methods around the 2009/2010 general practitioners enter in the software delays. Preliminary results indicate that, flu season, when the pandemic flu vaccine used in practice. CPRD currently contains using CPRD, there is power to detect large was introduced with limited safety information on over 4 million active increases in risk for rare adverse drug information. This type of patients. reactions and increases in risk for more surveillance is now routinely frequent adverse events. Further results of used by the VSD CPRD DATA DIFFERS from other data this work will enlighten the researchers on sources already used to perform near real- how to best use CPRD data to implement time vaccine safety surveillance. Therefore a near real-time vaccine safety surveillance it is necessary to assess whether it fulfils system. The final results are expected to certain requirements to implement strengthen vaccine pharmacovigilance near real-time surveillance, and the systems in the UK. best way to implement this type of surveillance. As mentioned, one of the key aspects of a near real-time system is access to timely data, and one of Andreia Leite the first steps in the PhD Student, London School of implementation process is to Hygiene & Tropical Medicine assess delays. [email protected]

26 UPPSALA REPORTS / ISSUE 76 INSPIRE. ENGAGE. TRANSFORM INSPIRE. ENGAGE. TRANSFORM ISSUE 76 / UPPSALA REPORTS 27 Tech update Tech update

SING STANDARDS from the start ensures improved quality, less manual work, and quicker processing Drug-name of information throughout the entire pharmaco- Digital reporting made available vigilance system, from the patient to global drug safety systems and back. look-up in mobile When reporting suspected adverse drug reactions reliable identifi cation of a medication to Montenegrin pharmacists used is vital. However, it is not enough to only apps made easier know details about the medication suspected of causing a drug- Pharmacists in Montenegro’s public sector can now use a digital relatedU problem. It might be an unexpected medicine that is responsible for the problem or an interaction between two or application as an easy and efficient way to report adverse effects The WHODrug country list look-up more medicines. Therefore, reliable identifi cation of concomitant medications is also important. In addition, for issues such as quality- directly to the country’s Agency for Medicines and Medical Devices. related problems it is important to know the actual brand or trade service is piloting a new channel for name of the product – not only its active ingredients. Even though pharmacovigilance professionals may all agree that easier access to structured and quality- it is important to have correct and detailed information about a HARMACISTS PLAY AN important Before offi cially commissioning the on to the WHO global ICSR database, patient’s medicines, the use of quality-assured and standardised role in post-marketing monitoring reporting application, CALIMS conducted VigiBase, via the VigiFlow management assured medicinal product information, information sources for medicinal products hasn’t been as widely of drugs. They are both drug training for pharmacists – the future users system. Amendments to the country’s Law adopted as it could be. However, good sources are available; within experts and the healthcare workers of the new reporting forms. Under the on Medicines envisage the possibility for tailored for use in mobile reporting Pwho are the most important link between guidance of Pharmacovigilance Department patients to report directly to CALIMS, WHO’s drug monitoring programme, information about medicinal products has been collected and structured in the global dictionary patients and prescribers. The direct contact employees, all trainees successfully tested which has not been the case so far. In the apps and other data-collection tools by WHODrug since 1968. The dictionary is optimised for use within that pharmacists have with patients provides the new application and showed great near future, CALIMS expects that patients pharmacovigilance and clinical trials. It is available as text fi les them with the opportunity to monitor the interest and willingness to use it. and healthcare professionals will use the countries in the WHO Programme for and integrated in tools such as WHODrug Insight, VigiFlow and safety of treatment by reporting adverse The development of this digital application online form. VigiLyze. effects, and to participate in the development is one more step towards improving the International Drug Monitoring. of pharmacovigilance as an evidence-based cooperation between CALIMS and SEVERAL ORGANISATIONS have asked Uppsala Monitoring Centre scientifi c discipline. As the most important pharmacists, which will ultimately improve Nemanja Turković for an easy way of getting access to a simple list of medicinal product source of information for the effi cient and public health and patient safety. Offi cer, CALIMS names to include in e.g. mobile apps and various data collection safe application of over-the-counter [email protected] tools. Rather than handling the complexity of the entire dictionary, medicines, pharmacists also play a key role ANOTHER DEVELOPMENT in Montenegro is which contains detailed information about products from around in monitoring this category of drugs. the implementation of eReporting, which is Maja Stanković Head of Pharmacovigilance 130 countries, all they need is a small subset of WHODrug that is available via the CALIMS website since Department, CALIMS relevant for their region. In addition, new types of tools, using new PREVIOUSLY, PHARMACISTS in the public March this year. The eReporting module [email protected] technologies, also require new ways of accessing information. sector in Montenegro could only report allows national pharmacovigilance centres to collect reports of adverse effects directly In late 2016 UMC decided to address this need by providing easy adverse effects by fi lling out a hard copy of Veselinka Vukićević access to subsets of WHODrug for usage within the Programme. A the reporting form. However, in July 2016 from patients as well as healthcare Offi cer, CALIMS project was launched with the WEB-RADR project as a pilot user, the possibility to report digitally through the professionals, which are then further passed [email protected] and in February 2017 UMC successfully launched a web service that healthcare information system – which they makes this possible. use in their daily work – was introduced. The service makes a country-specifi c subset of WHODrug The system links all pharmacies in the available, containing information about medicinal products with public sector to other participants in the their trade names and active ingredients. There is no graphical user , including the Agency for interface; instead the service is intended to be integrated in other Medicines and Medical Devices of tools, such as the mobile app developed in the WEB-RADR project. Montenegro (CALIMS). In this manner, In this tool the service is used to present a list of medicinal products the supply and consumption of medicines in for the user to pick from. The selected product can then be used to pharmacies is monitored, which is essential retrieve news, get safety information, and report adverse events. for conducting analysis in the fi eld of The new WHODrug service is up and running, servicing the rational pharmacotherapy. mobile app developed in the WEB-RADR project. It will be This digital application mimics the evaluated within the scope of the WEB-RADR project and after classical paper reporting form. After evaluation, it will be decided if it should be offered for a broader use. successfully entering data into the application, pharmacists send the report directly to CALIMS. The reports become Magnus Wallberg automatically available to CALIMS’s Technology Evangelist, UMC Pharmacovigilance Department, which [email protected] @CMWallberg is very important in cases when prompt regulatory action is needed. Nemanja Turković and Maja Stanković from CALIMS during training for pharmacists.

28 UPPSALA REPORTS / ISSUE 76 INSPIRE. ENGAGE. TRANSFORM INSPIRE. ENGAGE. TRANSFORM ISSUE 76 / UPPSALA REPORTS 29 In brief In brief

Join the conversation More transparency in on social media! clinical trial reporting N MAY 2017 some of the world’s largest devices, and it can even lead to use of medical research funders and non- suboptimal, if not harmful, products. The governmental organisations signed an new standards will require all clinical trials agreement to implement WHO to be registered in a publicly-available Istandards on reporting clinical trial results. registry and the results to be disclosed About half of all clinical trials conducted within specifi ed timeframes on the registry today go unreported, often because the and/or by publication in a scientifi c journal. results are negative. Incomplete reporting Most trials and their results will be leads to altered perception of the risks and accessible via WHO’s International Clinical benefi ts of vaccines, drugs and medical Trials Registry Platform.

15 million reports in VigiBase VigiBase is The number of individual case safety growing fast! reports in VigiBase surpassed 15 million in April 2017. “This is an impressive achievement by member countries in the WHO Programme! Their contribution is key to advancing global pharmacovigilance 5 million practices and for using data to million 10million improve patient safety,” said Anki 15 Committee on Safety of Medicinal Products (ACSoMP) held its 14th annual meeting at WHO headquarters in Geneva in April. The WHO Advisory Hagström, the head of UMC’s Global 2009 2015 2017 Services department.

Ecuador and El Salvador new WHO PIDM members

Ecuador and El Salvador joined the Dr Tedros Adhanom Ghebreyesus is the new Director-General of WHO. The former Minister WHO Programme for International of Foreign Affairs in Ethiopia was elected by the Drug Monitoring as its 126th and World Health Assembly in May and began his 127th full members in April. fi ve-year term on 1 July 2017.

4th Asia Pacifi c PV training course Apply now! JANUARY 29 – FEBRUARY 09

UMC and ISoP have entered a three-year agreement to collaborate on pharmacovigilance training. UMC Mysuru, India director Marie Lindquist and ISoP president Sten Olsson signed the agreement at WHO headquarters in More info on www.who-umc.org Geneva in April.

30 UPPSALA REPORTS / ISSUE 76 INSPIRE. ENGAGE. TRANSFORM INSPIRE. ENGAGE. TRANSFORM ISSUE 76 / UPPSALA REPORTS 31 Pharmacovigilance Meetings 2017

6-8 July 2017 10-14 September 2017 11-12 October 2017 8th Global Pharmacovigilance & 77th FIP World Congress of Pharmacy Assessment and Medical Evaluation Drug Safety Summit and Pharmaceutical 2017 of Individual Case Safety Reports Kuala Lumpur, Malaysia ∙ Conference Series Ltd Seoul, Republic of Korea ∙ International Fareham, UK ∙ Drug Safety Research Unit (DSRU) www.globalpharmacovigilance. Pharmaceutical Federation (FIP) www.dsru.org pharmaceuticalconferences.com www.fip.org/seoul2017 @DSRUDrugSafety @GlobalPharma17 @FIP_org 15-18 October 2017 12-14 July 2017 25-27 September 2017 17th Annual Meeting of ISoP XI Congreso de Farmacovigilancia y Advanced Pharmacovigilance Liverpool, UK ∙ International Society of Tecnovigilancia de la AMFV London, UK ∙ Management Forum Ltd Pharmacovigilance (ISoP) León, Guanajuato, México ∙ Asociación Mexicana www.management-forum.co.uk www.isoponline.org de Farmacovigilancia (AMFV) @ISoPonline www.facebook.com/farmacovigilanciamex 26-28 September 2017 th @AMFVmx 4 Annual and 24-26 October 2017 Pharmacovigilance Summit 2nd Annual Risk Management and 23-25 August 2017 Vienna, Austria ∙ Allan Lloyds Pharmacovigilance America Summit XIV Encuentro Internacional de www.AllanLloyds.com Boston, US ∙ Allan Lloyds @AllanLloyds Farmacovigilancia de las Américas www.AllanLloyds.com Bogotá, D.C., Colombia ∙ Colegio Nacional de @AllanLloyds Químicos Farmacéuticos de Colombia 4-5 October 2017 [email protected] Risk Benefit Assessment in 9-10 November 2017 Pharmacovigilance Signal Detection and Regulatory 26-30 August 2017 Fareham, UK ∙ Drug Safety Research Unit (DSRU) rd Expectations 33 International Conference on www.dsru.org London, UK Pharmacoepidemiology & Therapeutic @DSRUDrugSafety Management Forum Ltd Risk Management 5 October 2017 www.management-forum.co.uk Montreal, Canada ∙ International Society for Pharmacoepidemiology (ISPE) An Essential Overview of 4-6 December 2017 www.pharmacoepi.org Pharmacovigilance Pharmacovigilance @ICPE London, UK ∙ Management Forum Ltd London, UK www.management-forum.co.uk Management Forum Ltd 4-6 September 2017 www.management-forum.co.uk 4th ISoP – UMC Pharmacovigilance 8-10 October 2017 Training 17th Annual Conference of Society of Panama City, Panama ∙ International Society of Pharmacovigilance Pharmacovigilance (ISoP) & Uppsala Monitoring Srinagar, India ∙ Society of Pharmacovigilance, Psst! Follow us on social Centre (UMC) India (SOPI) media for news and updates. www.isoponline.org; www.who-umc.org www.sopi.net.in @ISoPonline @UMCGlobalSafety www.linkedin.com/company/ 9-11 October 2017 Uppsala-Monitoring-Centre 4-15 September 2017 Building Teratovigilance Capacity Vaccine Pharmacovigilance Fellowship in Africa Accra, Ghana ∙ WHO Collaborating Centre for Cape Town, South Africa ∙ Centre for Infectious www.facebook.com/ Advocacy and Training in Pharmacovigilance Disease Epidemiology and Research (CIDER) UppsalaMonitoringCentre www.who-pvafrica.org www.buildingteratovigilance.co.za @who_acc @uctcider www.twitter.com/ 6-7 September 2017 10-11 October 2017 UMCGlobalSafety Back to Basics in Pharmacovigilance Uppsala Health Summit Fareham, UK ∙ Drug Safety Research Unit (DSRU) Uppsala, Sweden ∙ Uppsala University www.dsru.org www.uppsalahealthsummit.se www.youtube.com/c/ @DSRUDrugSafety @Ua_HealthSummit UppsalaMonitoringCentre

Uppsala Monitoring Centre (UMC) is an independent non-profit foundation and centre for international service and scientific research. Our vision is a world where all patients and health professionals make wise therapeutic decisions in their use of medicines. Our mission is to support and promote patient safety through effective global pharmacovigilance practise. 32 UPPSALA REPORTS / ISSUE 7672 INSPIRE. ENGAGE. TRANSFORM