UMC Activities 

Overview - areas of work of the Uppsala Monitoring Centre

WHO Drug Dictionary

Coding

Analysis

DD Browser

The WHO Drug Dictionary has been used for more than 30 years. To access more information, visit the WHO Drug Dictionary pages.

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WHO Adverse Reaction Terminology

WHO-ART is made in English, but has also been translated into German, French, Spanish, Portuguese and Italian. WHO-ART files are released on a quarterly basis. A paper print edition of WHO-ART is issued annually.

WHO-ART to MedDRA bridge

In 2008 UMC implemented MedDRA in the WHO ICSR database to make it as compatible with MedDRA as it has been with WHO-ART. All report data fields accepting WHO-ART have been made to allow either WHO-ART or MedDRA terms and all outputs will display both WHO-ART and MedDRA. Vigibase now provides a global repository of MedDRA-coded safety data that can be used as a substantial tool for pharmacovigilance.

The latest version is WHO-ART 09.1 to MedDRA 12.0. The mapping contains all WHO-ART preferred terms with a link to closest MedDRA terms which may be on either Low level or Preferred level, also giving codes for both WHO-ART and MedDRA terms. This mapping is 'one-sided' in that it links WHO-ART terms to MedDRA terms, but should not be used the other way around. The mapping is intended for WHO-ART users who may want to be able to present or send data in MedDRA terminology to others and is provided as a txt-file free of charge to all WHO-ART and MedDRA customers.

Ordering

For details about purchase of WHO-ART (and information leaflets in Adobe Acrobat format in English and French) please refer to relevant pages of the UMC Products & Services website.

VigiFlow: a validated case management system for pharmacovigilance centres and companies

Software is now available from the UMC for pharmacovigilance centres that are in need of a modern system for management of adverse reaction reports. Since 2001 the UMC has been collaborating with the Swiss medicines agency, Swissmedic (IKS), on the challenge of improving ADR reporting and feedback in the age of the internet.
The web has made possible the creation of a channel for improved communication between reporting and prescribing physicians and a pharmacovigilance centre. When the Swiss national centre needed to upgrade their systems, instead of building something completely new, the UMC worked with them to develop a parallel ADR database with the WHO database. This software 'VigiFlow' has been made available from the UMC for pharmacovigilance centres in need of a modern system for management of adverse reaction reports (there is a charge depending on country size and GDP), and it is hoped in the future it will be suitable for others using drug information databases.

The system accesses Vigibase over the internet, so no local installations are required, and thus no licenses of database systems and servers. Reports can be entered and assessed via a secure internet connection by the doctor reporting an ADR. The report is then accessed by assessors from a regional centre and the national centre (click on diagram for full view).

The development together with the Swiss agency has guaranteed a solution that solves the basic needs of a National Centre, and can be developed to add new useful functionality:

This innovative and seamless system can be copied or adapted for other National Centres, and a growing number are using it for managing their ADR reports. It can be developed further by adding additional tools, and this development can be shared by the National Centres that want to use the additional modules. Potential add-ons to facilitate the use of UMC services such as Signal document, Combinations database are planned.

The process of developing and maintaining VigiFlow has been validated: the GxP validation process of version 3.0 was described in Uppsala Reports 32.

Version 4.1 of this sophisticated case report management system was released in June 2009 (see Uppsala Reports 46).

A User Group for VigiFlow held its first meeting in Uppsala on 20 October 2008 and again in Rabat on 4 November 2009. If you want to know more about the project please contact Sten Olsson.

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Searching the WHO database

New and improved VigiSearch

VigiSearch is a powerful search tool that provides access to all active case reports in VigiBase. All National Centres have access to this information. In the simple search mode a user can specify a drug and/or a reaction, and possibly date criteria. Drugs can be entered at different levels from highest ATC levels to the lowest level (which is the specific trade name of a drug). Adverse reactions can be entered in a similar fashion. Recent improvements include a more extensive search interface in the advanced search mode, more information on an overview level for case reports and detailed pdf printouts.

VigiMine

VigiMine is a new development within VigiSearch, making the IC values and other statistics available online, and replacing the 'combinations database' which was distributed by CD to National Centres. The advantages are numerous, including easy access to IC values for ALL drug-ADR pair combinations in the database (not only those of the latest quarter), more frequent updates (currently monthly, in future more frequent), and the availability of statistics stratified by age, gender, age+gender, country and reporting year. Time-scan data is also available, ie the development of the IC values over time. There are still a lot of functions left to expand within both VigiSearch and VigiMine, including developing output formats to enable management and printing of the data, and functionality such as filtering and sorting are on the agenda. (See pages 10-11 of Uppsala Reports 44 for a full report.)

The use of Data-mining for signalling adverse drug reactions

One of the main aims of the WHO programme is to highlight previously unknown drug safety problems. To facilitate the analysis of the WHO database, we have developed a framework for effective knowledge discovery in spontaneous reporting drug safety data sets.

The core of this data mining methodology is a Bayesian measure of association referred to as the Information Component (IC). The IC allows for robust large scale screening for quantitative associations in the database. A simple application is to highlight drug-ADR pairs that occur unexpectedly often together on case reports. A triage algorithm based on this and other information is in routine use to prioritise case series for clinical review. The Bayesian Confidence Propagation Neural Network (BCPNN) and other methods for complex pattern recognition are used to generate hypotheses related to for example syndromes and ADR risk factors.

This award-winning (item in Swedish) data mining tool has been routinely used since 1998 for the early detection of possible new side effects of drugs and has produced internationally high profile findings see, for example, the BBC News website. The tool uses Bayesian statistical principles in a neural network architecture to perform unsupervised pattern recognition. The project itself has presented in both Microsoft Magazine Sweden (1998) and Dagens Nyheter (1998). Moreover, we have developed an award-winning method to highlight suspected duplicate case reports in post-marketing drug safety data sets. 

Our data mining framework is used to analyse a range of other datasets as well. Please contact Niklas Norén for more information!

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Pandemic Flu Vaccine Monitoring

The UMC has set up a webpage where you can find which country uses which A/H1N1 vaccine, which country publishes AEFI reports on the internet with links, links to SPCs (Summaries of Product Characteristics) of A/H1N1 vaccines, and other useful links. [Click here]

We hope that the information can support the efforts of monitoring agencies and public health organizations in communicating about pandemic influenza vaccine safety issues and that the information can support the analysis of AEFI (Adverse Event Following Immunization) data. This will especially valuable for the countries to which WHO will ship vaccines. This webpage is maintained in close consultation with WHO-IVB. Please notify us of corrections and additional information to update the existing tables at: vaccine@who-umc.org  

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Monitoring of herbal medicines

Plants have been the primary source of food and medicine for people of every culture throughout the world. However, practitioners of traditional medicine need to be more aware of the problems of toxicity. Infrequent adverse drug reactions will not be recognized without the existence of a formal system of reporting negative experience. Physicians who have patients taking any particular medicinal plant should try to document negative experiences, in order to gather enough scientific information about the adverse effects of the herb. Adverse drug reaction reports are a critical source of herbal drug safety information. the UMC is grateful to all who are reporting suspected herbal adverse reactions to a national centre.

The renewed interest in the western world for plants used in traditional medicine, and the rapidly growing interest in developing countries to start research programs in this area have, unfortunately, not emphasized the great importance of taxonomic botany and documentation for such research. There is a need to adopt the most commonly used binomial names (including their binomial synonyms) for medicinal plants, to eliminate the confusion created by the common names. Artemisia absinthium L. for example, contains an active narcotic derivative, which can cause central nervous system disorders and generalized mental deterioration. This herb has at least 11 different common names (wormwood, absinthium, absinth, absinthe, madderwort, wermuth, mugwort, mingwort, warmot, magenkraut and herba absinthii), 7 of which bear no resemblance to its botanical name. Because mainly common names are used, Heliotropium europaeum (heliotrope), containing pyrrolidine alkaloids, potent hepatoxins, is often confused with Valerian officinalis (garden heliotrope), containing valepotriates, which act as a sedative and muscle relaxant in laboratory animals.

The exact scientific name of the plant, the plant part used and the name of the manufacturer are very important pieces of information when writing ADR reports on herbal medicines. Solving the existing problems requires the collaboration of botanists, phytochemists and pharmacologists.

the Uppsala Monitoring Centre has undertaken a project with the aim of attaining global standardization for herbal medicines. The scope was to standardize information about herbal medicines, including their scientific names and therapeutic implications, which can vary widely between countries. The structure of the ATC-system, developed for classification of orthodox medicines, was used as a basis for the Herbal ATC structure (see Publications, Herbal ATC Classification). The UMC collaborates with the Department of Botany, Uppsala University and the Royal Botanical Gardens at Kew in the UK, and with other international experts.

The UMC is carrying out research on 25,000 herbals of Chinese origin to identify acceptable scientific names. An example of a multi-ingredient herbal preparation is Yi Xian Wan which shows herbal ingredients, elements of animal origin and minerals, all of which require accurate identification.

In the WHO database, as of May 2009, there were 34,084 suspected herbal case reports where only herbal substances are involved and 18,813 reports which include both herbal and non-herbal substances. The most commonly reported reactions are:

The most commonly reported critical terms for adverse drug reactions on herbal drugs are:

We need more reports - and more accurate information!

Herbal ATC Classification

the Uppsala Monitoring Centre has published Guidelines for Herbal ATC Classification and Herbal ATC Index. For various reasons it has been deemed impractical to incorporate hundreds of herbal remedies in the regular ATC classification. However, experience from the ATC system - particularly in connection with the monitoring of adverse effects of drugs - has shown that such a system would also be suitable for herbal remedies.
In 1998, De Smet proposed a system for ATC classification of herbal remedies which is fully compatible with the regular system. With a few modifications this system has now been adopted and is given in the guidelines. The Herbal ATC Index list Herbal ATC (HATC) codes per substance, while the Guidelines for Herbal ATC Classification helps to assign HATC codes to herbal remedies. In both the ATC and Herbal ATC systems remedies are divided into groups according to their therapeutic use. Whenever possible the level 1-4 codes in the herbal system are equal to the levels in the regular ATC system.
So far we have been dealing with single herbs; now the UMC has begun assignment of herbal ATC combinations, and it is hoped that the next issue will contain combination assignments. 

If you are interested in these publications, please contact info@who-umc.org.

The WHO Herbal Dictionary

The WHO Herbal Dictionary (WHO-HD) is the first international dictionary of herbal products. It is used for identifying the standardised names of herbal products, their active ingredients and therapeutic use in the course of their drug safety surveillance. It translates a drug name to useful information for coding and analysis of drug safety data both pre- and post- marketing.
The information routinely recorded by the UMC refers to all drugs of natural origin and herbal substances, whether or not suspected of causing an ADR, mentioned in all international ADR reports submitted to the WHO Programme since its beginning in 1968, as well as products entered from other sources, such as IMS Health and the Chinese SFDA.
The products entered in the WHO Herbal Dictionary are those that only contain herbal ingredients. Products that contain a mix of herbal ingredients and conventional medicines appear in the WHO Drug Dictionary.

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Monitoring Medicines

The UMC is acting as co-ordinator for a major international project, funded by the European Commission, aiming to improve drug safety. The ?Monitoring Medicines? project will run for 3½ years, and aims to learn more about why adverse drug events occur so that we can act to reduce patient deaths and negative health impacts arising from undetected medicines safety problems globally. A dedicated website is accessible via this link: www.monitoringmedicines.org

The UMC is also one of the partners in the PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Consortium) project, which aims to strengthen the monitoring of the benefit-risk of medicines in Europe by developing innovative methods. Their website is here: PROTECT

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Pharmacovigilance in public health programmes

The UMC is involved in initiatives based on the drug treatment of HIV/AIDS, malaria and tuberculosis that major donors (Global Fund, Gates Foundation etc) are currently undertaking through public health programmes in countries where only rudimentary systems for pharmacovigilance exist, if at all. Many of the medicines employed by the public health programmes are new and/or have associated safety concerns.

Our work includes collaboration on the establishment and training of a pharmacovigilance field force to actively assemble case information from the treatment centres of the public health programmes. Other organisations provide staff to enter this data into country-specific databases, using the VigiFlow software from the UMC. A team of signal reviewers will be trained to analyse the collected case information and to highlight any indication of new patient safety concerns. Such information will be provided to programme managers and regulatory authorities in each country in which the system is operating and to the international community when considered relevant.

UMC has a key role by providing a number of services:

• Training of the field force regarding the collection of relevant patient and case details
• Access to the VigiFlow software for management of individual case safety reports
• Training for VigiFlow users
• Provide tools for data analysis
• Training of staff in case assessment, signal analysis and benefit/harm evaluation
• Communicating results to relevant national authorities and international partners.

Further information about the initiative may be gained from www.rapidpharmacovigilance.org , or by contacting Sten Olsson at the UMC (sten.olsson@who-umc.org).

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UMC Activities page last updated 29 July 2010