Assessment of the Community System of Human Pharmacovigilance
Recommendations for systems, knowledge and resources
Initiatives in Denmark
Pharmacovigilance and perspectives nationally and in the EU
In 2004, the EU Commission decided to launch an assessment of the existing system for monitoring of medicinal products, primarily to enable an assessment of the need for potential and possible improvements. In December 2004 following a tender, the Commission chose an independent institution (Frauenhofer) to perform an “Assessment of the Community System of Human Pharmacovigilance”. The work began in January 2005, and the final report was published on the website of the EU Commission on 16 March 2006. It is currently in public hearing.
The report was based on a questionnaire survey, interviews and data gathered and made available by the European medicines agencies. The interviews were carried out during 1-day visits at the national medicines agencies as well as at the European Medicines Agency (EMEA). A consultant visited the Danish Medicines Agency on 1 May 2005. Therefore, all data and information provided to the consultant dates back to the period prior to 1 May 2005.
The report does not contain complete individual assessments of national medicines agencies. However, some of the tables and figures in the report do give an impression of conditions in Denmark compared with other countries. For example, the number of adverse drug reaction reports per number of inhabitants is rather high in Denmark compared to most other countries. Another example is that the number of adverse drug reaction reports about children and young people is relatively low. Thus, the report hints at relevant focus areas in Denmark.
Recommendations for systems, knowledge and resources
The main conclusions of the comprehensive report (chapter 10) contain recommendations for improvements of the spontaneous reporting system, in which establishment of regional centres may be a useful tool. Regional centres can positively influence the frequency and quality of adverse reaction reports, but the EU report shows that this is particularly true for large countries, such as France, and in particular if combined with performance contracts. In Denmark, there are hardly any benefits to reap from further regional division, as the population base already corresponds to that of a large regional centre in the large EU countries.
Moreover, the report recommends professional training for health care professionals about monitoring of medicinal product safety, possibility for users to report adverse drug reactions themselves and easier and faster access for doctors to new knowledge about safety information. In general, there seems to be a need for the authorities to improve communication with all interested parties concerning medicinal product safety as well as for the effect of this effort to be measured.
The marketing authorisation holder (MT), a pharmaceutical company, is responsible for monitoring the safety of its own products. It is recommended that the authorities strengthen cooperation with MT holders, hereunder that the authorities intensify the control of MT holders. One way of doing this is by carrying out Pharmacovigilance inspections.
Generally, it is recommended that authorities have sufficient scientific and technical resources for tasks related to adverse drug reactions, and access to internal and external experts. There are also recommendations about using and improving quality control, as well as about relocation of resources, which should be possible if necessary.
Initiatives in Denmark
Several initiatives in Denmark are already improving the monitoring according to the recommendations of the report. By a legislative change in 2003, Denmark became the first country in the EU to introduce the possibility of receiving adverse drug reaction reports from consumers. The Council for Adverse Drug Reactions was founded at the same time. It is the task of the council to advise the Danish Medicines Agency about general problems in connection with monitoring and communication of safety issues. In 2003, the Danish Medicines Agency also became authorised to perform inspections of companies of manufacturers of medicinal products – also with a view to inspect their procedures for and quality of adverse drug reaction monitoring. By the establishment of the Consumer Safety Division in 2005, the Danish Medicines Agency took a further step towards strengthening the communication and dialogue between relevant interested parties within the adverse reaction area.
Besides from adverse drug reaction reports and safety updates, which pharmaceutical companies are responsible for producing, there is a need for more knowledge and information from other sources in order to confirm or invalidate a signal. Some of the things considered here are register surveys and/or pharmacoepidemiological studies. The new EU adverse drug reaction database (EudraVigilance), to which all serious adverse drug reactions in the EU are reported, is going to contain reports from a population of around 500 million, and authority access to this database is going to be very important when it comes to generating signals. As appears from the report, the number of adverse drug reaction reports in the Danish database is modest, but the Danish population is only 1/100 of the total European population and the Danish reports are part of the total international quantity of knowledge. With the access to the common European adverse drug reaction database, even the small EU countries have improved possibilities of gaining access to large amounts of data.
Pharmacovigilance and perspectives nationally and in the EU
Besides from what relates to the recommendations of the Frauenhofer report, there is a range of other initiatives that have been taken to strengthen Pharmacovigilance in the EU and in a national context. The list below is not exhaustive.
A revision of the European legislation, with effect from November 2005, ensures a more proactive approach to monitoring the safety of using medicinal products, both before and after the marketing. Steps have been taken to improve the possibilities for discovering and assessing risks, reduce them and communicate effectively with relevant interested parties.
In 2002, the Heads of Medicines Agencies (HMA) in cooperation with the European Medicines Agency (EMEA) established a group that was to work specifically with medicinal product safety and initiatives concerning risk management: the European Risk Management Strategy Facilitation Group (ERMS) (ERMS summary report, 2003 and ERMS press release 16.12.2005).
In 2002 and 2004, ERMS carried out two questionnaire surveys (ERMS survey) with the purpose of giving an overview of the resources available to Pharmacovigilance as well as on what tasks these resources were primarily used. Much of the data gathered is included in the report from Frauenhofer.
Based on these studies, among other things, EMEA and the HMA have drawn up a list of future aims for improving Pharmacovigilance in the EU. These aims are described in strategy papers from EMEA and HMA as well as in a common work programme (ERMS work programme 16.12.2005 and ERMS strategy paper 11.05.2005). The main cornerstones in the common European strategy are to ensure:
- fast and efficient implementation of new legislative initiatives
- evidence-based decision-making
- rational use of resources
- utilisation of modern technology for gathering and processing of data
- effective execution of authority tasks, hereunder ensuring that interested parties comply with legal requirements
- on-time and relevant information about safety issues
All significant safety issues concerning medicinal products are handled by the PharmacoVigilance Working Party. To strengthen the function of this group, a range of experts within paediatrics, geriatrics, vaccines, pharmacoepidemiology and communication were recently attached.
Simultaneously with the Commission’s study, the area is mapped through different benchmarking and audit projects. This, together with the knowledge gathered in the day-to-day work nationally and internationally, means that it is possible to draw a varied picture of the monitoring of medicinal product safety in the EU. This is a prerequisite in order for authorities and the Commission to jointly take the initiatives necessary to continuously ensure monitoring of a high quality and an appropriate use of resources for the benefit of consumer safety.
For further information, please contact Chief Medical Officer Doris Irene Stenver on tel.: +45 4488 9247 or Director of the Consumer Safety Division Elin Andersen on tel.: +45 4488 9287.
The Danish Medicines Agency, 21 March 2006
