Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
WHO Collaborating Centre for International Drug Monitoring The WHO Programme for International Drug Monitoring The Uppsala Monitoring Centre Monica Plöen WHO Collaborating Centre the Uppsala Monitoring Centre • Established as a foundation 1978 • Based on agreement Sweden - WHO • International administrative board • WHO Headquarters responsible for policy • Self financing UMC activities WHO Programme Funding Commercial sector activities WHO Drug Dictionaries UMC organization Director Marie Lindquist Finance and Core services Birgitta Toreheim 6 people Marketing Annika Wallström 11 people Safety Support and Services Monica Plöen 22 people External Affairs Sten Olsson 5 people Research Niklas Norén 7 people Production, Development and Quality Johanna Eriksson 17 people WHO Drug Monitoring Programme Founding Members 1968 19 68 19 70 19 72 19 74 19 76 19 78 19 80 19 82 19 84 19 86 19 88 19 90 19 92 19 94 19 96 19 98 20 00 20 02 20 04 20 06 20 08 Member countries 1968-2009 100 90 80 70 60 50 40 30 20 10 0 Cumulative number of correct reports processed per year Country Distribution in Vigibase October 2009 VigiSearch/ VigiMine WHO-ART Custom Searches WHO database VigiBase WHO Drug Dictionary MedDRA E2b Intdis Eudravigilance Home-built tools Home-built tools Win ADR National Centre VigiFlow National Centre (simple entry tool) VigiFlow – a software for management of ADR case data • SwissMedic 2001 • Free text possible • Web based • Mandatory fields • E2B format • Error checks • Less report delay • National database UMC Function 1 Signal detection • Primary UMC task • Identification of previously unknown drug reactions Signal WHO definition • • Reported information on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously. Note: – A signal is an evaluated association which is considered important to investigate further. – A signal may refer to new information on an already known association. – Usually more than a single report is required to generate a signal, depending upon the seriousness of the event and the quality of the information. Advantages of computerized signal detection • Necessary for huge databases • Automatic, no time loss • Objective, unbiased • Reproducible • Flexible (adjustable) Method developed by the UMC • BCPNN – Bayesian Confidence Propagation Neural Network • Select combinations ”standing out”, for clinical review – Represented by a high value of Information Component (IC) IC interpretation • IC = 0 : Combination reported as often as expected relative to the background • IC > 0 : Combination reported more frequently than expected • IC025 > 0 : Also the lower value of the 97,5% confidence interval is higher than expected from the background "1988:1" "1989:1" "1990:1" "1991:1" "1992:1" "1993:1" "1994:1" "1995:1" "1996:1" "1997:1" "1998:1" "1999:1" "2000:1" "2001:1" "2002:1" "2003:1" SSRI Neonatal convulsions or neonatal withdrawal syndrome All SSRI 6 4 2 0 -2 -4 -6 Signal Detection & Follow-up Combinations.db (reported quarterly) Triage (filter) Quarterly analysis BCPNN Vigibas e National Centres Triage filter - selection of associations • IC025 > 0; two or more countries • Quarterly IC increase of 1 or more • New drugs and serious ADRs irrespective of IC value • (Target reaction terms (e.g. SJS), two or more reports, irrespective of IC value) Literature check Signal Detection & Follow-up Combinations.db (reported quarterly) Triage (filter) Quarterly analysis BCPNN Review panel Vigibas e National Centres Signal review panel • 40 experts from around the world • Evaluate signals, together with UMC staff and National Centres • Select associations for follow-up • Write signals in the SIGNAL document The SIGNAL document • Sent to all National Centres • Individualized section available to industry • All recipients encouraged to comment on topics presented Or published in WHO Pharmaceutical Newsletter Some WHO Signals detected with data mining Drug Safety Issue Quantitatively highlighted WHO Signal Accepted as drug related Topiramate -glaucoma 2nd quarter 2000 April 2001 October 2001c Infliximab – pericardial effusion 4th quarter 2001 Dec 2002 August 2004c Infliximab- vasculitis 2nd quarter 2000 Sept 2002 August 2004c SSRIs – neonatal convulsions 4th quarter 1999 Dec 2001 May 2005a Abacavir – MI 2nd quarter 2004 May 2005 April 2008b A Confirmatory literature review B RCT showing increased risk C Labelling change UMC functions 2 • Signal strengthening – Web-based search programme (Vigisearch/Vigimine) – Search requests Data available to non-members • By request to WHO Collaborating Centre • To degree health professionals • Caveat document UMC functions 3 • Comparing national experiences International Differences (Quantitative and Qualitative) • • • • • • • • • Disease prevalence Genetic Social Cultural Healthcare systems Health professional practices Indication for, and use of medicines Pharmaceutical formulations Drug monitoring practices UMC functions 4 • Identification of risk factors Potential Risk Factors • • • • • • • • Other drugs Sex/gender Age Genetic constitution Dosage Duration of treatment Route of administration Indication WHO Drug Dictionary • A source of international drug names • Includes all drugs reported to VigiBase • Information on MAH, form, strength, source etc. • Drugs classified according to the ATC (AnatomicalTherapeutic-Chemical) classification system • Ingredient names according to INN WHO herbal ADR database Valid scientific botanical names • No internationally standardized and accepted classification of all botanical names of medicinal herbs exist • the UMC has created a list of preferred botanical names and their synonyms The common name problem Common name Botanical name Chemical relation Chinese, Asian Ginseng American Ginseng Tienchi Ginseng Siberian Ginseng Russian Ginseng Brazilian Ginseng Wild red Am. Ginseng Alaskan Ginseng Wild Ginseng Ayurvedic Ginseng Ginseng of the Andes’ Panax ginseng Meyer Panax quinquefolius L. Panax pseudoginseng Wall. Eletherococcus senticosus Maxim. Acanthopanax senticosus Harms. Rumex hymenosepalus Torr. Pfaffia paniculata (Mart.) Kunze. Echinopanax horridum (Sm.) Decne. Aralia nudicaulis L. Withania somnifera (L.) Dunal Lepidium meyenii Walpers Standard Similar Similar Different Different Different Different Different Different Different Different Technical support to the WHO Programme • Guidelines – Why and how to set up PV centres • Terminologies – WHO Adverse Reaction Terminology – WHO Drug Dictionary • Software development – – – – – Vigiflow Paniflow CEM-flow Vigisearch/Vigimine DD Browser UMC involvement in local activities 2005-2009 • 2005 – India, Germany, Moldova, Turkey, Italy, Poland, Argentina • 2006 – Uzbekistan, Brazil, Barbados • 2007 – India, Nepal, South Africa, Ghana, China, UAE • 2008 – Namibia, Philippines, India, Botswana • 2009 – Uganda, Saudi Arabia, India, Tanzania, Nigeria, Mozambique UMC - a communication centre • WHO Pharmaceuticals Newsletter • Uppsala Reports • Internet home page http://www.who-umc.org • Vigimed e-mail discussion group Thank you for your attention! Process for joining WHO Programme 1. Ministry of Health (or equivalent) designates National Centre 2. Ministry of Health sends formal application to WHOHQ, Geneva Ministry of Health 2 5 5. WHO-HQ advises Ministry of Health of admittance to the Programme National Centre 3 3. National Centre sends sample reports to the UMC 4. UMC notifies WHO-HQ that reports are compatible 1 the UMC WHO-HQ Geneva 4