Valproate Pregnancy Prevention Programme

Backbench Business - Services for People with Autismbackbench Business – in the House of Commons at 5:00 pm on 21st March 2019.

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Motion made, and Question proposed, That this House do now adjourn.—(Jeremy Quin.)

Photo of Cat Smith Cat Smith Shadow Minister for Voter Engagement and Youth Affairs, Shadow Deputy Leader of the House of Commons

I am raising the issue of the valproate pregnancy prevention programme today as a result of tireless campaigning by my constituent Janet Williams. Along with her friend Emma Murphy, Janet, who is here today, launched the Independent Fetal Anti-Convulsant Trust, or INFACT, in November 2012, and they have almost single-handedly kept the issue of disabilities caused by anticonvulsant medication on the political agenda since then. Despite both living in the north-west of England, they regularly travel to and from London to demand action from drug companies, politicians and civil servants, and they simply will not take no for an answer. Mr Deputy-Speaker, you may know that when a woman from Lancashire gets her teeth into something, she is not going to let go. The campaign for justice and to ensure that no families are similarly affected continues, but the fact that progress has been made in recent years is largely down to Janet and Emma.

It may help if I first provide some background to sodium valproate. The drug, a trade name of which is Epilim, is manufactured by Sanofi, among others, and has been prescribed in the UK since the 1970s. Despite its effectiveness for treating certain types of seizures, research has demonstrated that it carries a higher level of risk to the exposed foetus. Around 27,000 women are currently taking sodium valproate in England and Wales. Scientific data demonstrates that around 10% of children exposed to sodium valproate will be born with a major congenital malformation and their IQ is likely to be lower, with 29% requiring additional educational support and 6% being diagnosed with significant social communication difficulties such as autism.

Estimates of the number of children still being affected by this drug vary. In February 2016, Norman Lamb, the then Minister for Life Sciences, stated that 336 children are exposed to valproate every year. Figures from the Clinical Practice Research Datalink suggest that the figure could in fact be 176. However, even the lower number would imply that 7,000 children have been harmed by valproate since it first came on the market in 1973, with a further 28 a month still exposed to it.

Sodium valproate received its licence to be prescribed in the UK in 1973. The first case reporting the effects of sodium valproate during pregnancy appeared in 1981. By 1987, the damages caused by the drug in pregnancy were recognised throughout the medical professional, being given the title of foetal valproate syndrome in 1995. National Archive documents show that the Committee on Safety of Medicines was aware of the dangers of valproate when taken in pregnancy at the time of licensing, but it decided to inform medical professionals while keeping the women taking the medication in the dark. The patient information leaflet for sodium valproate was only changed to highlight the risks during pregnancy in 2000, and the information was sparse even then.

Women and children have been let down by the pharmaceutical industry and successive Governments over many decades, and I hope that they will one day be compensated for the failures that were allowed to occur. However, I want to focus the remainder of my time on addressing how we can ensure that all women of childbearing age taking sodium valproate today are aware of the risks it poses and are able to make informed decisions about their future.

The valproate toolkit was introduced in March 2016 and gave healthcare professionals the opportunity to inform patients voluntarily of the dangers of taking valproate in pregnancy. Sadly, the toolkit failed to achieve its aims. It took the form of a patient booklet, pharmacy cards that were received on collection of a valproate prescription, a healthcare professional booklet and a checklist for specialists.

INFACT surveyed patients and pharmacists, and the two surveys found that around 85% of patients were not receiving the patient booklet and 90% were not receiving the pharmacy card. In a letter from Sanofi on 27 May 2016, INFACT was informed that the patient booklets were not given to GPs, as had previously been indicated by Ministers, but instead had to be downloaded by GPs from the Sanofi website. In designing the pregnancy prevention programme, what lessons have been learned from the failure of the valproate toolkit?

The pregnancy prevention programme, as a mandatory action, was introduced in April 2018 following the failure of the valproate toolkit, which gave healthcare professionals the opportunity to discuss the dangers of valproate with their patients. It was stated:

“To protect public health, the Medicines and Healthcare products Regulatory Agency (MHRA) has changed the licence for valproate medicines (Epilim, Depakote and generic brands). Valproate must no longer be prescribed to women or girls of childbearing potential unless they are on the pregnancy prevention programme (PPP)…
Healthcare professionals who seek to prescribe valproate to their female patients must make sure they are enrolled in the PPP. This includes the completion of a signed risk acknowledgement form when their treatment is reviewed by a specialist, at least annually.”

As with the valproate toolkit, the PPP included a booklet to enable patients to understand the risks and a small, credit card-sized information card for pharmacists to provide on dispensing the drug. However, the PPP was strengthened by the addition of an “acknowledgment of risk” form, which was to be signed by the doctor and the patient on the communicating of the risks. For the pharmacist, there was the addition of ensuring that every dispensed prescription of valproate included the patient information leaflet, the credit card-sized information and warning stickers on the white chemist boxes, all of which had been supplied by Sanofi on the instruction of the MHRA.

To get to this stage, numerous meetings had been held over a five-year period to discuss how the information would be designed to be most instructive both to the healthcare professional and the patient, working through the valproate stakeholder network meetings and the expert working group meetings at the MHRA. Following the failure of the first toolkit, patient groups are understandably on guard to ensure they are aware of problems. Worryingly, over a 10-month period INFACT found that the majority of women were not receiving the new pregnancy prevention programme from their doctor or pharmacist.

From December to February, INFACT collected information through a survey of 74 women, which showed: 80% received the white chemist boxes; 40% never received the patient information leaflet, and 41% received it only some of the time; and 78% had never received the small credit card-sized information, with the majority of them never having had warning stickers on their white chemist boxes. During appointments with healthcare professionals, approximately 40% had never discussed the PPP with their doctor, more than 60% had never been asked to sign the “acknowledgment of risk” form, and 73% had never had alternative medication suggested to them.

Those figures indicate that women continue to be failed by their healthcare professionals and pharmacists on the PPP, even though its legislative status has been recognised, with instructions given by the General Pharmaceutical Council to pharmacists and by the MHRA to healthcare professionals.

In the autumn of 2018 proof of the failure, in the form of videos and photographs, was passed to the MHRA and, in turn, to the enforcement agency for investigation, yet we are still awaiting a response to those investigations. The consequences of these findings are deeply troubling. They indicate that women and girls aged between 15 and 45 may still not be being given an informed choice about their medication. They are not being given any information about alternative medications that may be suitable for them, and they are not being asked to sign the “acknowledgement of risk” form by their GP or specialist. On collection of their valproate prescription, they are not receiving any instruction from the pharmacist, nor are they receiving the small credit card-sized information, the patient information leaflet or any warning stickers on the white boxes.

It is worth reiterating that approximately 27,000 women of child-bearing potential are still prescribed sodium valproate every year; that 70% of them have not been offered a change in their medication since April 2018 and the introduction of the PPP; and that approximately 19,000 women are therefore still at risk of becoming pregnant while being prescribed valproate with no instructions from either their doctor or their pharmacist.

In addition to the risks outlined earlier, INFACT has been made aware that folic acid does not have the desired affect when taking sodium valproate and that the dangers to the foetus are no longer dose-related, making it a possibility that all those exposed to valproate in the womb will be affected by it. I would therefore like to ask the Minister to clarify: what assessments have been done to ensure women prescribed valproate receive the PPP and are offered an alternative medication where possible? What assessments are taking place to calculate how many healthcare professionals, including GPs in surgeries and those in pharmacies, complete the PPP with their valproate patients? And what the enforcement agency intends to do to ensure those failing to comply with the PPP have penalties imposed to ensure they do not continue to do so? Finally, I would like to request that the Minister meet me and representatives from INFACT to discuss how we can make sure the PPP works for women, allowing them to make informed choices about their own health and the health of potential future children.

Photo of Stephen Hammond Stephen Hammond Minister of State (Department of Health and Social Care) 5:11 pm, 21st March 2019

It is a pleasure to respond to this debate on behalf of the Government, and it is an honour to follow 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 anti-epileptic 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 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 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.

House adjourned.