WHO Drug Information Vol. 30, No. 1, 2016 Safety of medicines The WHO Collaborating Centre for International Drug Monitoring Detecting and addressing medicines-related problems is critically important for patient safety. As the manufacture and supply of medicines becomes more globalized, so too should the approaches to monitoring the safety of vaccines and medicines. WHO, through its Programme for International Drug Monitoring, works with the Uppsala Monitoring Centre (UMC) to maintain the world’s single global repository of data on adverse drug reactions and to promote good pharmacovigilance practices in Member States. Background decisions and safety signals for medicinal Pharmacovigilance is the science products at a global level. and activities relating to the detection, assessment, understanding and WHO Programme for International prevention of adverse effects or any Drug Monitoring other drug-related problem (1). Although An important part of WHO’s medicines all medicines are rigorously tested in safety work is the Programme for clinical safety and efficacy trials before International Drug Monitoring (PIDM). The they are made publicly available, most WHO PIDM members submit Individual of the safety data on medicines only Case Safety Reports (ICSRs) into a global becomes known once the products are database. on the market. Continued monitoring in The ICSRs submitted by member real world settings, where medicines are countries are managed by the WHO used in conjunction with other products, Collaborating Centre for International among different patient populations and Drug Monitoring, known as the Uppsala in patients with multiple illnesses, is Monitoring Centre (UMC)1. With over therefore critically important. one hundred staff and consultants, WHO promotes medicines safety UMC carries out a wide range of in Member States in several ways. activities to support and promote The organization develops normative patient safety through effective global guidance with a focus on low- and middle- pharmacovigilance practice. The centre income countries, supports countries in maintains relationships with hundreds implementing best pharmacovigilance of individuals, institutions, professional practices, and communicates regulatory societies, research units, government 1 www.who-umc.org This article is based on the Annual Report 2015 of the Uppsala Monitoring Centre (UMC) (2). We thank Paula Alvarado and Lembit Rägo for their useful input. 24 Pre-publication draft - page numbers are not for citation purposes WHO Drug Information Vol. 30, No. 1, 2016 Safety of medicines Figure 1. Participation in the WHO Programme for International Drug Monitoring (PIDM) Number of WHO PIDM member countries 120 122 12000 111 104 10000 91 81 70 75 8000 60 53 6000 41 46 32 4000 22 24 14 16 19 ICSRs in VigiBase™ 10 2000 0 1968 1970 1972 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016 departments and commercial operations. In 2015, aggregated safety data from UMC receives a sustained flow of VigiBase became accessible to the public guidance through the WHO Advisory through the launch of VigiAccess™ 2. Committee on the Safety of Medicinal Products (ACSoMP) and WHO-appointed Research UMC Board members. With VigiBase as the sole global database of safety information, the detection and A global database dissemination of signals of suspected drug The core repository of ICSRs submitted safety concerns is a major focus of UMC’s globally is the VigiBase™ database, which work. A total of 42 signals were detected, is developed and maintained by the UMC assessed and published in 2015. on behalf of WHO. Identifying safety signals is rather like In December 2015 there were 122 WHO finding needles in haystacks. The UMC’s PIDM member countries and a cumulative research team is continuously seeking total of over 11 million ICSRs submitted to new and better ways of recognizing VigiBase (Figure 1), including more than medicinal problems early in order to one million reports from low- and middle- protect patients. Some examples include: income countries. From 2017, VigiBase • detecting syndromes, when more than will receive ICSRs transferred by the one ADR is reported and there is a European Medicines Agency (EMA) on a need to group reports with similar ADR daily basis (see also page 57). profiles; UMC has developed a range of data • finding risks in specific populations management and analysis tools in support (paediatrics, vaccines, geographical of VigiBase, notably the web-based regions); ICSR management system VigiFlow™ • highlighting case series with sufficient – provided free of charge to WHO PIDM information for assessment; members as a limited-access version • detecting signals in electronic health enabling electronic ICSRs reporting – and records; the search and analysis tool VigiLyze™. 2 www.vigiaccess.org Pre-publication draft - page numbers are not for citation purposes 25 Safety of medicines WHO Drug Information Vol. 30, No. 1, 2016 • developing software to analyze free-text to leverage mobile-phone reporting and narratives in case reports; find ways to analyze social media for • detecting substandard drugs; and pharmacovigilance purposes. • exploring the potential of social media In 2009–2013 UMC coordinated the as a source of patient risk information. Monitoring Medicines project, a multi- Members of the UMC’s research team regional pharmacovigilance and public contribute to professional meetings and health effort funded by the European research conferences and have won Commission (3). This project was international awards for their work. developed by WHO and brought together UMC also contributes to external diverse parties to develop methods, tools collaborative projects. Examples and guidelines for pharmacovigilance include the PROTECT project aiming to and resulted in significant synergies. Its strengthen the benefit-risk monitoring outputs illustrate how pharmacovigilance of medicines in Europe by developing activities can serve to detect, assess, and validating new signal detection understand and prevent not only adverse methods, the SALUS project aiming to reactions to medicines, but also threats develop tools and protocols for mining to patient safety caused by other drug- and analyzing real-time patient data related problems such as product quality from heterogeneous electronic health deficiencies or inappropriate use of records, and WEB-RADR, which aims medicines (Table 1). Table 1. The Monitoring Medicines project: addressing medicines-related safety issues Stated objectives Outputs 1. Support and strengthen consumer WHO handbook (4) reporting of suspected adverse drug Online reporting system (used in six pilot countries, reactions (ADRs) offered free of charge to all VigiFlow users) 2. Expand the role and scope of national WHO handbook (5) pharmacovigilance centres to identify, analyse and prevent medication errors 3. Promote better and broader use of existing Methodology for detecting drug dependence in pharmacovigilance data for patient safety spontaneous adverse drug reaction databases (6) Methodology for detecting substandard or counterfeit medicines (7) 4. Develop additional pharmacovigilance Publication on WHO strategy for collecting safety data in methods to complement data from public health programmes (8) spontaneous reporting systems Cohort event monitoring (CEM) Web-based data management tool CemFlow (used in Belarus, Kenya, Nigeria, Tanzania and Zimbabwe) Targeted spontaneous reporting (TSR) WHO handbook on pharmacovigilance of medicines used for tuberculosis (9) Clinical use of pharmacovigilance data Web-based database and risk assessment tool in anti- retroviral therapy, available at www.hivpv.org Source: Adapted from: (3). More information about the Monitoring Medicines project available at: www.monitoringmedicines.org. 26 Pre-publication draft - page numbers are not for citation purposes WHO Drug Information Vol. 30, No. 1, 2016 Safety of medicines Terminology and coding tools In 2015 UMC organized or participated The data collected in VigiBase are in pharmacovigilance training courses in also the source of the content for the Asia, Africa, South America and Europe. WHODrug™ Dictionary portfolio. This Two major events were the 17th annual UMC resource aims at optimizing the pharmacovigilance training course global analysis and reporting of medical held in Uppsala with participants from product information during the whole life 28 countries, and the first Asia-Pacific cycle of a drug. WHODrug is mandated Pharmacovigilance training course in in Japan and recommended in the United Mysore, India, organized in collaboration States for concomitant medications in with JSS University. clinical trials. It is regularly updated with In addition, UMS held webinars on a new releases and components to support range of topics in five languages and its use in specific contexts. The 2015 launched a YouTube channel providing releases include an Enhanced version access to over 150 training sessions. produced in collaboration with IMS Health, the Cross Reference Tool Japan and the Advocacy Cross Reference ATC 5. In 2015 UMC launched its first public A mapping bridge has been developed campaign, Take&Tell™ 3, encouraging between the WHO Adverse Reaction patients to tell their health professionals Terminology (WHO-ART) and MedDRA, about adverse effects. This innovative the standard terminology of the and unique campaign raised much International Council for Harmonization interest around the