Five years ago, in July 2012, the European Union’s new pharmacovigilance legislation came into effect, representing the biggest change to the regulation of human medicines in the European Union (EU) since 1995. With the full support from the industry, the intent was to address as a matter of urgency, the estimated 197,000 deaths per year in the EU that were the result of adverse drug reactions (ADRs), or ‘noxious and unintended’ responses to a medicine. 

In order to achieve its goal, the legislation promoted: the collection of better data on medicines and their safety; the rapid and robust assessment of issues related to the safety of medicines; effective regulatory action to deliver the safe and effective use of medicines; the empowerment of patients through reporting and participation; and increased levels of transparency and better communication. EFPIA welcomed the adoption of the legislation and its members have remained very engaged in its implementation.

The enhanced focus on transparency has seen the European Medicines Agency this week launch a revolutionary and potentially valuable tool, aimed at increasing the involvement of patients and citizens in the regulatory decision-making process: the Pharmacovigilance Risk Assessment Committee’s (PRAC’s) public hearings.

Public hearings are designed to complement the EMA’s existing channels for engaging with patients and healthcare professionals in the assessment of medicines. They are guided by a pre-defined set of questions, are open to all members of the public and are conducted in English. Nevertheless, the emphasis falls on the word “hearing” according to Juan Garcia Burgos, the EMA’s Head of Department for Public Engagement: “We are listening, we cannot engage in a specific debate.”

By addressing directly the concerns of those most affected by PRAC recommendations, the hearings should help improve citizen’s understanding of benefit-risk considerations associated with every medicine. As Linda McAvan MEP put it at her opening speech of the first ever PRAC Public Hearing on Sodium Valproate, which took place on 26 September 2017: “We wanted more public engagement in medicines safety, to bring more transparency into the system.” An additional, positive, complementary effect of these hearings will be an increased public confidence in regulatory decisions. 

First licensed in 1973, valproate has been used in Europe to treat a range of different diseases and conditions, including epilepsy and bipolar disorder, and, in some countries, migraine attacks. It is also in the World Health Organization’s (WHO’s) List of Essential Medicines.

Though acknowledged widely as an effective treatment in these areas, and approved and followed in post-marketing phase through regulators’ scrutiny, valproate was discovered to be teratogenic – that is, it posed a serious health risk to unborn children exposed in the womb. Specifically, valproate was found to present up to 30 - 40% risk of developmental problems and circa 10% risk of birth defects. There is also a suggestion of a lower risk linked to autism. Administration, therefore, in pregnant women, should be approached with extreme caution.

The first public hearing was addressed by members of the general public (including patient representatives, carers, families), a representative from the pharmaceutical industry, several healthcare professionals and academics. The information offered ranged from very real reports about how the drug had a devastating effect on the lives of children and their parents, to factual information about why the drug was administered, in what circumstances, what options may have been available, and what information has been given to the patient.

The hearing was told that there are very real challenges still faced by health services in disseminating information on the potential serious adverse effects of the use of valproate during pregnancy. While, for example, a universally-acknowledged “excellent” toolkit on the risks of valproate medicines in female patients available in the UK, delegates reported that the majority of female patients – and indeed healthcare professionals ­– did not seem to be aware of its existence due to a variety of reasons. 

Several HCPs highlighted the fact that while the drug represented a potential hazard in pregnant women, it continues to be a useful and sometimes the only medication effective for in some types of epilepsies with no other treatments. Moreover, simply withdrawing the drug, once administered in these patients, is not without risks. The key, therefore, is getting the benefit-risk balance right – and this is the purpose of the public hearing. Valproate is an important treatment that many women continue to rely on to control seizures during their lifetime, including during pregnancy. It should be acknowledged that there is a real dilemma faced by doctors and women who have no other alternatives to control their seizure.

So what’s being done and what could be improved? A number of ideas were suggested to the PRAC. 

Pharmacists are well placed to provide expert knowledge and more resources should be made available to ensure there are expert pharmacists available for people with epilepsy. Annual medication reviews could be made available to patients who are treated with valproate, particularly during their pregnancy. There needs to be more effort to get the right information to the right person at the right time. Restrictions should allow for a distinction to be made between girls and women of child-bearing potential and those that are already pregnant. Also, further research should be conducted on what role the genetic differences of women taking valproate play in the context of understanding whether some children are more vulnerable to the effects of anti-epileptics. Where an effective contraceptive device is administered, seizure control through use of valproate can be achieved safely. An expert European panel should be formed to guide HCPs’ use of antiepileptic drugs in women of child-bearing age. There are several ways in which the education of patients and HCPs could be undertaken in a more effective and modern way.

All this is not only food for thought for the PRAC but also for EFPIA member companies. EFPIA’s pharmacovigilance expert group provides an excellent platform from which the pharmaceutical industry can advance in this area and its experts are considering currently what kind of risk minimisation measures are the most effective. Further dialogue with regulators and other stakeholders will be needed. 

Closing the public hearing, the Chair of the PRAC, June Raine suggested that the EMA’s Report on the meeting would be available in about two weeks’ time. This would be followed by more scientific discussions in next month or so within the PRAC and its’ representatives from all Member States. Real regulatory action, based on input from the public hearing would be undertaken after two-to-three months at a minimum, depending on the scientific discussions. 

Public hearings represent a real opportunity for Europe’s medicines authority to engage fully with public and improve health across the EU accordingly. Nevertheless, as one delegate put it: “If at the end of this nothing changes, then we will feel that the exercise has been a lot of a waste of important people’s time.”