Dr. Almath Spooner:

That would be a concern for the HPRA and all of us working to ensure that these medicines are used safely by those who need them but not in pregnancy. We will be working collaboratively with patient groups and the HSE on this issue. We received notification last week from the Health Research Board in regard to an application in which we sought to do academic collaborative work with the RCSI that would bring some independent perspective to analyse drug utilisation data to make sure that these measures are effective in practice. I appreciate that members will have anecdotes of situations where practice needs to adapt. We need systematic evidence to be generated to ensure the measures are working in practice and that women who are at risk are not being exposed. We will be undertaking this work with patient groups and academics.

The pharmacovigilance risk assessment committee, PRAC, was established in 2012. It was the product of amendments to European legislation, which I am sure many members have followed. PRAC was established as a committee independent of the licensing committee. It was given regulatory teeth and its outcomes are binding. At the time of its establishment, recognising the public health importance of this issue, this was one of the very first reviews we did. I am vice chairman of that committee and I am doing all I can to make sure that this is robustly addressed in terms of analysing the scientific data but also following through on other issues. As rightly said by my colleagues, this is the first example of a referral in which we have undertaken a look-back in terms of whether measures are working or if we need to do more and the answer was yes.

We can only do that using a collective multi-stakeholder approach. We regulate the products and now need to ensure the knowledge of the harm associated with the medicine leads to changes in clinical practice.

I emphasise and acknowledge that we are talking about a chronic condition. Deputy Kate O'Connell referred to Isotretinoin, but members will appreciate indications and population. Acne is very different from epilepsy. We have concerns and do not want to have unintended consequences. Switching a woman's prescription from sodium valproate to an alternative requires time, but it requires specialist expertise, in particular. That is why the PRAC has made it a requirement of the licence that an annual review be conducted by a specialist when sodium valproate is prescribed for women with a credible risk of pregnancy. That is not a provision attached to a licence lightly; it is simply to recognise the importance of the health risk.

Some Deputies addressed the common theme of why identifying the risks had taken so long. As the congenital defects are visible, members can understand why they were identified early on. Warnings about such risks were issued right from the beginning. However, as neurodevelopmental disorders are more subtle, it takes time to make a link with exposure in utero. Deputy Stephen S. Donnelly made an astute observation on delays, but I wish to emphasis that we are not talking about delays but disorders. The PRAC has clearly outlined that they are disorders where children do not catch up in their development. That is something that came through very clearly in patient testimonies. We understand the magnitude of the risk. We understood there was the potential for harm if sodium valproate was used in pregnancy. What we have seen over time is an evolution in the understanding of the risk and its magnitude and the impact on children and their families. That understanding has been facilitated by the fact that, as a committee, the PRAC has focused on hearing directly from patients. It has both a public health focus and a patient engagement focus. The way we conduct pharmacovigilance today differs greatly from what it was in the 1980s. One aspect is the new data streams, a new willingness to engage with patients to hear about their experiences.

Another aspect is the epidemiology evidence required to make a link. That evidence was unavailable in the 1970s and 1980s. The first of the research papers came through around 2008. It was a Meador et al landmark study which, as some Deputies mentioned, provided the most robust evidence of a causal link between neurodevelopmental problems and the treatment. There is convergence and an acceptance of the risk. As Deputy Stephen S. Donnelly mentioned, it is difficult to make a causal link at an individual patient level. However, we know, based on the epidemiological studies, that 11% of patients have physical defects, about 30 to 40 have neurodevelopmental problems, within which there will be a spectrum, by which I mean that some patients will be more severely affected than others. The data stream on which we have relied is the epidemiological evidence, rather than trying to make individual causality assessments which, by definition, is very difficult.

On the questions posed by Deputy Kate O'Connell, I hope I answered her question about referral to a specialist for an annual review. I have explained that when treatment is initiated, concern about harm in pregnancy might seem a remote concern. That is why, as part of the global package of measures, we have advocated for the avoidance of the use of sodium valproate in young females, with a view to reducing the complexity involved for individual patients, given all they could suffer in the healthcare system in having to ultimately transition from one treatment to another. Our goal into the future is to prevent exposure to sodium valproate in pregnancy. At one of the stakeholder meetings Mr. Peter Murphy of Epilepsy Ireland said we must move beyond process to impact. My organisation is in full concordance with him on that point.