Joint press release
7 December 2010

A series of public health disasters serve to remind us of the importance of effective, proactive pharmacovigilance (a). The benfluorex (Médiator°) scandal in France this year  has illustrated the point well. At least 500 people died due to an unacceptable delay in decision-making (b). The European Parliament approved the pharmacovigilance proposals in September 2010 (a Directive and a Regulation). These proposals were then adopted by the Ministers for Health of the Member States on 29 November 2010 .

Dangerous original proposals, improved by Members of the European Parliament
The European Commission’s original proposals on pharmacovigilance would have meant a major step backwards in the protection of European citizens, with:

• “conditional” marketing authorisations becoming the norm, behind the smokescreen of “risk management systems” that, in reality, are used by pharmaceutical companies to bring inadequately-evaluated medicines to the market prematurely (c);
• pharmaceutical companies being entrusted with the task of collecting and interpreting the data on the adverse effects of their products, despite the conflict of interest.

Thanks to the mobilisation of civil society and the numerous amendments adopted by the European Parliament’s Committee on Environment, Public Health and Food Safety (ENVI), the European Commission’s original proposals were greatly improved. The improvements included:

• clarifying of the role of risk management systems: it is now specified that they must not be used as a pretext for granting premature marketing authorisations;
• strengthening the authority of the new European Pharmacovigilance Risk Assessment Committee (PRAC) relative to the Committees of the Agencies in charge of marketing authorisations (Committee for Medicinal Products for Human Use [CHMP] and Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human [CMDh]);
• giving patients the right to report adverse drug reactions of medicines in all Member States;
• having patients report adverse drug reactions to health authorities, rather than to pharmaceutical companies, as was originally planned;
• granting public access to the agendas and detailed minutes of meetings of European Medicines Agency (EMA) committees, although access is still not granted for the content of the Community database on adverse drug reactions (Eudravigilance).

However, two major backward steps remain:

• Member States will no longer be required to provide public funding for pharmacovigilance systems, which will jeopardise the independence of pharmacovigilance systems (d);
• pharmaceutical companies will code adverse effects and enter this data directly into the European Eudravigilance database, with the risk that clinical cases will be distorted and therefore difficult to interpret (e).

A missed opportunity to genuinely strengthen the European pharmacovigilance system
The adopted proposals are not ambitious enough: they do not deliver the overhaul of the system that was needed.

If patient safety is to be truly strengthened, the following actions would be required:

• marketing authorisation should only be granted by regulatory authorities for drugs that have been shown to provide a tangible therapeutic advantage for patients compared to the reference treatment (‘gold standard’): this would prevent patients being exposed to the risks of new drugs that offer no additional benefit over existing treatments but whose adverse effects are unknown to a large extent;
• a system should be set up that would strongly encourage health professionals to systematically report the adverse effects they observe, particularly serious adverse effects, even if these effects are already known; the objective should be to obtain accurate data on the frequency of adverse effects occurring in “real-life", so that a medicine’s risk-benefit balance can be thoroughly reviewed and, when necessary, decisions made to safeguard public health;
• there should be much more transparency of pharmacovigilance data so that independent analyses and warnings can be produced, which would support a more proactive approach to pharmacovigilance;
• drug regulatory authorities need to make appropriate, timely decisions, particularly the European Medicines Agency (EMA) in the case of an urgent procedure. The primary objective of drug regulatory authorities must be to safeguard public health (f).

Patient safety as a public health priority
Established but dangerous medicines should not be allowed to continue harming patients (for example, the weight-loss drugs benfluorex (formerly marketed under the brand name Médiator °, withdrawn from the European market in November 2009 after 30 years on the French market) and sibutramine (formerly marketed under the brand name Sibutral°, withdrawn in March 2010 after 9 years on the European market)). And the proliferation of new major pharmacovigilance scandals (Vioxx°, Accomplia°, Avandia°, etc.) must be stopped. We therefore call on the European Commission’s Directorate-General for Health and Consumers to rapidly propose more ambitious measures.

If the safety of European patients is to be genuinely reinforced, the European Commission’s priorities must be:

• to improve the quality of the evaluation of medicines before they are granted marketing authorisation;
• to increase the independence of drug regulatory authorities, to enable them to better fulfil their public health remit, particularly when evaluating and reviewing the harm-benefit balance of medicines.

Health Action International (HAI) Europe
Medicines in Europe Forum (MiEF)
International Society of Drug Bulletins (ISDB)

> Click here to download the Joint Press Release (pdf, 141 Ko)

© Medicines in Europe Forum December 2010

Notes:
a - For example: the malformations that affected children born to mothers who had taken thalidomide during pregnancy in the 1960s and diethylstilbestrol (D.E.S.) (Distilbène°) in the 1970s; the adverse cardiovascular effects associated with the anti-inflammatory drug rofecoxib (marketed under the brand name Vioxx°, withdrawn from the European market in 2004) or the antidiabetic drug rosiglitazone (marketed under the brand name Avandia°, recommended to be withdrawn from the European market by the European Medicines Agency (EMA) in 2010), and the adverse psychological effects (including an increased risk of suicide) associated with the weight-loss drug rimonabant (marketed under the brand name Accomplia°, withdrawn from the European market in 2008), etc.
b - Benfluorex (Médiator°) is a drug indicated as an adjuvant diabetes treatment, although any evidence for its efficacy was very limited. In reality this amphetaminic substance has been widely used for a long time as a weight-loss drug. It took the determination of a French pulmonologist, who conducted a case-control study, for the decision to be taken to withdraw benfluorex (Médiator°) from the French and European market, and yet its extremely serious adverse effects (which were responsible for at least 500 deaths in France, particularly due to heart valve deformities) had been withheld for a very long time!
c - These premature marketing authorisations result in the general public running the health risks inherent in a large-scale clinical trial.ç
d - Experience has shown the limitations of funding healthcare product regulatory agencies using the fees paid to them by pharmaceutical companies. The agencies find themselves in the position of service providers, working primarily for their clients, the pharmaceutical companies, a position that is incompatible with their remit to safeguard their population’s health.
e - If all adverse effects were required to go through Member States’ pharmacovigilance systems, it would enable the Member States’ competent authorities to:
- have a clear view of the adverse effects occurring on their territory;
- keep their national database up to date;
- make this information accessible to their country’s population in its own language.
It is not enough for reports, as entered in the Eudravigilance database by pharmaceutical companies, to be sent in parallel to the Member States’ competent authorities, because the data could be impossible to interpret in this form.
f - Their decisions must be based in particular on periodic independent reviews of drugs’ risk-benefit balance, even for medicines that have been authorised for a long time, using quantified indicators (for example, when the frequency of a known or suspected adverse effect rises above a level that seemed "acceptable" at the time marketing authorisation was granted).

References:
1 - “Council acts against adverse effects of medicines” Press release, Brussels, 29 November 2010. http://www.consilium.europa.eu/uedocs/cms_data/docs/pressdata/en/lsa/118080.pdf