Valproate Pregnancy Prevention Programme

Stephen Hammond Excerpts

Thursday 21st March 2019 Commons Chamber

[The Minister for Health (Stephen Hammond)]

It is a pleasure to respond to this debate on behalf of the Government, and it is an honour to follow the hon. Member for Lancaster and Fleetwood (Cat Smith), who has secured an important debate. I wish to pay tribute to her and her constituents from INFACT, whom she mentioned.

The hon. Lady has rightly set out that, as Members of this House will be aware, valproate is a very effective treatment for epilepsy and bipolar disorder. For a few women with epilepsy, it may be the only effective treatment, and she rightly recognised that in her speech. However, its use is associated with serious side effects in children exposed to it during pregnancy; there is a 40% risk of persistent developmental disorders and a 10% risk of physical birth defects. Valproate should therefore be used to treat women of childbearing age only if alternative drugs are ineffective or not tolerated.

In April 2018, strengthened regulatory measures for valproate were introduced. They include a pregnancy prevention programme that aims to rapidly reduce and eventually eliminate pregnancies exposed to valproate. The hon. Lady asked a number of questions about the PPP. The challenge is to ensure that valproate is used by only those who need it, that they are fully informed about the risks in pregnancy and that treatment is closely monitored. Let me emphasise that it is vital that no woman stops taking valproate or any other antiepileptic without discussing it with her doctor.

Valproate has always been known, since the time it was first licensed, to carry serious risks if taken during pregnancy. However, important questions have been raised about the extent to which women have been informed about the nature and magnitude of those risks over the decades. At the time valproate was first marketed in 1974, animal studies had shown that there may be a risk of birth defects. Health professionals were made aware of that and were expected to weigh the benefits against the risks. They were expected to prescribe valproate only in severe cases or those where there was resistance to other treatments. Difficult prescribing decisions sometimes had to be made.

Campaigners have highlighted minutes of a meeting of the Committee on Safety of Medicines in 1973—the hon. Lady referred to that—where it concluded that it would be best not to mention the risk of birth defects following the use of anticonvulsants in the information supplied with the medicine, but that doctors should be informed. At that time, it would have been the doctor’s responsibility to pass on information on side effects. Today, patients and doctors are expected to make decisions jointly, based on open communication about all the risks and benefits of a treatment.

Over the years, warnings have been issued to prescribers by the regulator when new evidence on risks in pregnancy has become available. In 1983 and 1993, communications went out to update prescribers on the growing evidence of the risks in pregnancy. In 2003 prescribers were warned about a possible risk of developmental delay in children exposed to valproate during pregnancy. Warnings were extended to include a risk of autism in 2010, and a further bulletin was issued in 2013. It was around that time that the full magnitude and nature of the risks of valproate in pregnancy first became known, following the long-term follow-up of cases of affected children.

Given the seriousness of the accumulating evidence, the Medicines and Healthcare Products Regulatory Agency initiated a major Europe-wide safety review of valproate in pregnancy, which was completed in November 2014. The conclusion was that the balance of the benefits and risks of valproate in epilepsy and bipolar disorder remained favourable in women of childbearing potential only when other drugs were ineffective. The MHRA went further than updating the statutory information, as required by the EU review, and developed the valproate toolkit for healthcare professionals and women, which consists of a set of clear and informative materials. More than 100,000 healthcare professionals have received the toolkit.

As the hon. Lady referred to in her speech, in the autumn of 2015, given the importance of the issue, the then Life Sciences Minister, my hon. Friend the Member for Mid Norfolk (George Freeman), brought together all the relevant healthcare bodies to support the promotion of the toolkit and ensure that co-ordinated messaging was given out to health professionals and patients. The MHRA further developed this group into a 39-strong stakeholder network of health system organisations, health professional bodies, charities and campaign groups, which has been convened 11 times to date, to raise awareness and to help to embed the new measures in practice.

Despite extensive work to communicate the risks of valproate, concerns about the limited impact of the action in the UK and other member states led to a further EU review, which in 2018 resulted in a strengthened regulatory position stating that valproate must not be used in women of childbearing age unless they comply with the requirements of a pregnancy prevention programme. All healthcare professionals who prescribe valproate to female patients must ensure that they are enrolled in the pregnancy prevention programme. That ensures that women must use effective contraception throughout their valproate treatment and have an annual review with a specialist, which includes the consideration of alternative treatments, and must sign an annual risk acknowledgement form.

I am sure the hon. Lady will know that in February 2018 the then Secretary of State, my right hon. Friend the Member for South West Surrey (Mr Hunt), announced that he had asked Baroness Cumberlege to lead the independent medicines and medical devices safety review, which is exploring what happened in the cases of valproate, Primodos and mesh and considering the robustness of processes, the quality of engagement with and response to patients’ concerns, and any wider lessons. As I am sure the hon. Lady does, I welcome that important work and look forward to seeing the recommendations from the review. It is vital, though, not to wait for the outcome of the review. Much work is being done, and will continue to be done, to ensure compliance with the valproate pregnancy prevention programme. We expect the review to report later this year. It has been consulting in a detailed and patient-orientated manner throughout the UK, with patients and relevant patient and healthcare organisations.

The hon. Lady raised a number of issues with the pregnancy prevention programme. The MHRA has monitored the impact of the programme closely since its introduction last year. Monitoring is being done via data from the clinical practice research datalink and national databases, which link data from community drug dispensing and maternity services. The MHRA is also accessing data from clinical audits run by healthcare professional organisations and information on patient experience via surveys.

Patient input and engagement with the patient group INFACT, to which the hon. Lady referred and which was started by her two constituents, has been invaluable throughout the process, as a source of both evidence and feedback on the implementation of action. The data shows a decline in the use of valproate in women of childbearing age, but we recognise that there is local variability. I am also aware of evidence of non-compliance by some healthcare professionals, which is of great concern. Non-compliance with the pregnancy prevention programme is not acceptable, and those concerns are being investigated to ensure that people are brought back into compliance. I can inform the hon. Lady that enforcement action will be taken as and when necessary.

The concerns that were raised in the survey that the hon. Lady referred to have led the UK chief pharmaceutical officers to contact all pharmacists to stress their responsibilities when dispensing valproate. This was reinforced by messages from professional regulators to their members and by articles in the MHRA’s electronic bulletin “Drug Safety Update” in September and again in December, making sure that all healthcare professionals recognise that they need to examine whether they are prescribing in compliance with the new measures.

Achieving full compliance with the valproate pregnancy prevention programme will require concerted action across the healthcare system. I recognise that there is more to do, but I stress again that healthcare professionals who prescribe the drug must make sure that their female patients are enrolled in the pregnancy prevention programme. As I have said, non-compliance is not acceptable.

The hon. Lady asked a number of other questions, some of which I hope I have answered during my speech. My noble Friend Baroness Blackwood specialises in this area and will take the lead in it. I know that she would be delighted to meet the hon. Lady and members from INFACT.

I thank the hon. Lady for highlighting this issue and pay tribute not only to her constituents, but to many other women who have spoken powerfully about the effects that valproate has had on their lives and the lives of their children. Their tireless campaigning has been vital in highlighting the further action that is needed to ensure that women know the risks and are helped to make an appropriate judgment about their treatment. It is vital, therefore, that all healthcare professionals work together rapidly to reduce and eliminate the exposure of pregnancies to valproate.

I hope that the action I have outlined today shows that steps are being taken to ensure that the necessary assessment, monitoring and, where necessary, enforcement action will be taken. In commending the hon. Lady, I hope that she, like me, will look forward to Baroness Cumberlege’s review, which, as I said, should be published later this year. I thank her once again for raising this important matter this afternoon.

Question put and agreed to.