EU Consultation Pharmacovigilance February 2008

Feb 2008

”The European Aids Treatment Group (EATG) welcomes the Commission proposal to strengthen pharmacovigilance aiming at establishing a genuinely European pharmacovigilance system by introducing a directive and a regulation amending the current legal provisions in place.

From EATG’s point of view, the proposed European pharmacovigilance system for centrally authorised products has the potential to substantially improve patient safety in Europe and to invigorate the European pharmaceutical sector, provided the way it is transposed by all Member States is successful in enhancing cooperation, communication and trust between the actors concerned.

The approach focuses on key elements to ensure patient safety

- by increasing the knowledge base about the safety of medicines,

- by establishing a clearer legal basis and setting up systems and mechanisms to bring about and facilitate compliance of the pharmaceutical industry in producing and sharing the necessary knowledge

- communication and transparency are given high importance

- streamlining and harmonising pharmacovigilance activities throughout Europe.

EATG appreciates that the proposal directly addresses all relevant stakeholders concerned (patients, patient organisations, health-care professionals, national authorities, EMEA, and the pharmaceutical sector), as EATG takes patient involvement at various levels of the pharmaco-vigilance process as instrumental in ensuring patient safety.

EATG fully supports the Commission’s draft proposing to

• enable fast robust EU decision making on safety issues by rationalising the existing EU referral procedures and reinforcing the committee structure by establishing a “Pharmacovigilance Committee” at EMEA, a committee with clear-cut responsibilities with the power to make binding decisions (3.2.1)
• clarify/codify the roles and responsibilities for industry and regulators, in particular by establishing the concept and scope of Good Vigilance Practices (GVP), with the aim to increase compliance by the pharmaceutical industry and to enhance quality management. (3.2.2)
• simplify informing the authorities about the company pharmacovigilance system (by introducing a “Pharmacovigilance System Master File”), thus reducing the administrative burden for pharmaceutical companies. (3.2.3)
• rationalise risk management planning - by providing a clear legal basis for risk management plans to be included at the time of marketing authorisation, requiring companies to include safety studies to include risk-management plans to be complied with. (3.2.4)

• codify the oversight of non-interventional safety studies – ensuring that non-interventional post-authorisation safety studies are of high quality, and clearly have health and not promotional objectives. (3.2.5)

• simplify and make risk-proportional single serious adverse drug reaction (ADR) case reports (3.2.6). In particular, EATG welcomes the fact that it will now fall upon the EMEA’s tasks to scan the scientific literature and to enter these case reports on Eudravigilance. Furthermore, EATG welcomes the transparency expected to ensue by establishing a publicly available list of intensively monitored products.

• Strengthen medicines safety transparency and communication – coordinate the communications of the Member States; EMEA maintain an EU portal on the safety of medicines; support the development of an EU drug dictionary; ensure coordinated communication about drug safety in order to send out clear messages to patients about specific safety risk issues, thereby increasing the safe use of medicines (3.2.8)

• Provide clearer safety warnings in product information to improve the safe use of medicines – allowing patients to rapidly identify key messages, introduce a new section in the Summary of Product Characteristics and Patient Information Leaflet on ‘key safety information – ensuring that key safety information is highlighted maximising the chances of it being read, understood and leading to risk minimisation (3.2.9)

EATG would like to raise some concerns and make suggestions concerning communication channels foreseen, most particularly regarding the Commissions intention to

• simplify and make periodic reporting by Marketing Authorisation Holders (MAH) proportionate to risk – linking Periodic Safety Update Reporting (PSURs) to risk promises to bring about more substantial knowledge about safety of the medicine in question, to increase transparency by establishing a list of medicines under intensive monitoring, asking patients and healthcare professionals to report all suspected adverse drug reactions (ADRs) to these products. (3.2.7)

EATG welcomes the fact that patients will be empowered to report adverse reactions themselves, and that patient reporting forms will be part of the information leaflet for intensively monitored drugs; and that for all other drugs reporting can be made directly to the national authority.
However, the proposal suggests that these reports are made to the Marketing Authorisation holders only, who shall then submit all adverse reactions reported within 15 days delay to the EMEA, wherever a causal relationship is at least “a reasonable possibility”. Although “reasonable possibility” is given a precise definition (laid out in Article 101 e[i]), EATG sees the following risk:

Patient’s trust in pharmaceutical companies’ effectively reporting adverse events has been damaged in the past, and the proposal does not address the challenge of how to reduce and deal with the inherent conflicts of interests of Marketing Authorisation Holders and individuals working in companies might have when it comes to reporting adverse events, or how negligence of this responsibility will be penalised.
Thus, the proposal foreseeing direct patient reporting of adverse events to Marketing Authorisation holders seems to rely on the very trust the proposed chain of communication of patient’s reporting of adverse events to the EMEA via the Marketing Authorisation Holder intends to bring about. The system seems too vulnerable, and the risk of the resulting damage in terms of public trust in the entire European pharmacovigilance system proposed in case of breach seems high.
If patients’ reporting to the MAH is to remain the only possibility, EATG would hope to see a safeguard introduced along the following line:

“Patients should be informed by the MAH that their report has effectively been communicated to EMEA and when this was done, with the possibility of patients turning directly to either the competent authority or the EMEA in case they have not been notified within the 15 days foreseen.”

Furthermore, in order to ensure reports submitted are of high quality, and more importantly the safety risks and worries of patients are effectively taken care of in due time, communication between patients and health-care professionals before reporting should be encouraged. EATG would like to suggest that the adverse event reporting form included in the patient leaflet specifically asks whether the adverse event in question has been discussed with a health professional.

EATG appreciates the fact that the current proposal foresees that the “Pharmacovigilance Committee” shall additionally include two members to represent health professionals, as well as two members to represent patient associations. However, although the importance of the work of patient organisations is frequently acknowledged at EU level, patient organisations do not receive core funding from the EU. In order to ensure patient representatives are appointed, appropriate compensation should be foreseen.

Furthermore, EATG would like to encourage communication and official affiliations between the “Pharmacovigilance Committee” and disease specific patient organisations, i.e. in discussions of results of safety studies and more importantly, and if possible prior to, publication of official recommendations and decisions about safety of medicines. Patient organisations are well placed to interface between authorities and their disease specific patient community, and could greatly contribute to the dissemination of information, especially when it comes to counterbalancing the potentially harmful effects of sensational press-reports. Sufficient additional funding should be provided for this.

Lastly, the EATG advocates for more stringent rules in case of non-compliance by industry. The pharmaceutical industry will benefit from a reduction of bureaucratic burdens by lighter and faster procedures. The potential benefits should be balanced by more stringent rules and sanctions in case of non-compliance. Therefore, art.101o should foresee penalties, not excluding the suspension of marketing authorisation.

a) Reports where the Patient or the Healthcare Professional has made a statement that a causal relationship between the event and the medicinal product is considered to be at least a reasonable possibility.
b) Reports where the Patient or the Healthcare Professional has not made any statement on the suspected causal relationship or has stated that the causal relationship is known but the temporal relationship between the exposure to the medicinal product and the adverse reaction means that a causal relationship can not be excluded.”

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