Cumberlege Report - 5 Years On

Introduction

The Independent Medicines and Medical Device Safety Review (Cumberlege report) was published on 8 July 2020. The report included nine general recommendations covering surgical mesh, Primodos and sodium valproate, in addition specific recommendations around sodium valproate.

On 11 January 2021, Nadine Dorries MP, the then Minister for Patient Safety, Suicide Prevention and Mental Health, provided the government’s initial response to the recommendations of the Cumberlege report.

The government finally responded in full to the main recommendations of the review on 21 July 2021. While they accepted some of the recommendations, key recommendations were rejected, and progress on many others remains slow despite the review now being five years old.

The purpose of this report by Epilepsy Action is to ensure that the recommendations of the Cumberlege Report are not lost and to hold government and others to account for their responsibilities.

The report’s recommendations are listed below, followed by the government’s response to each recommendation, Epilepsy Action’s verdict on progress towards implementing the recommendation and our recommendation for what needs to happen next.

Despite responding to the main recommendations of the Cumberlege report, the government has not addressed the valproate specific recommendations.

General Recommendations

Government response: Complete.

On 9 July 2020, the day after publication of the review, the government issued an unreserved apology on behalf of the healthcare system to the women affected, as well as their children and their families, for the time the system took to listen and respond.

Epilepsy Action verdict:

While we welcome the government’s apology, much more needs to be done to ensure that this apology is meaningful. We would urge the government to ensure that all of the report’s recommendations are implemented in full to ensure that the needs of these families are addressed.

Government response: Complete.

The government appointed Dr Henrietta Hughes as the Patient Safety Commissioner on 12 July 2022.

Epilepsy Action verdict:

While this development is certainly welcome, and the role of the Patient Safety Commissioner is important in working with the healthcare system to identify and resolve potential problems going forward, this new role will do nothing to help the 20,000 children who have already been harmed by valproate.

The Patient and Safety Commissioner has already been a powerful advocate for patient safety and will continue to do so. However, this also highlights the lack of advocacy that was provided to the families of those harmed by valproate.

In order to properly understand the historical failings that have led to the situation so many families are now in, the government should set up an inquiry into the historical licensing and use of sodium valproate in women of child-bearing potential.

And

Government response: “We did not accept recommendations 3 and 4 because our priority is to make medicines and devices safer, and the government is pursuing a wide range of activity to further this aim.

NHS Resolution has launched 2 claims gateways on their website to provide further support to patients who may wish to bring a clinical negligence claim in relation to pelvic mesh and sodium valproate.”

Epilepsy Action verdict: The government rejected the recommendation of a redress agency. This is hugely disappointing given the avoidable harm so many families have experienced. The problems that families harmed by valproate have experienced in pursuing compensation highlights the need for a redress agency as recommended. The government should reconsider their positions and establish a redress agency for cases of people being harmed by medicines and medical devices and urgently set up separate schemes for each intervention.

Although the government initially stated that it is “carefully considering” a separate redress scheme for those harmed by sodium valproate, it subsequently confirmed that a redress scheme will not be established. Instead, the government advised that affected families can pursue clinical negligence claims, which would be costly, difficult and time consuming. Many families have already spent large sums of money caring for children with diagnosed with Fetal Valproate Syndrome (FVS) and do not need the extra stress of pursuing clinical negligence claims.

The Patient Safety Commissioner has since published the Hughes Report, outlining options for providing redress for those harmed by valproate. Despite being published in February 2024, the government have still not responded to this report. The government needs to urgently announce a redress scheme for those harmed by valproate to ensure they get the support they need.

Many of the harmed children require additional support, including some who require 24-hour care, and this support would make a huge difference to their families.

In addition to financial redress, the government also needs to consider non-financial redress, such as housing, access to healthcare, creation of tailored healthcare pathways and services, educational support and social security.

Government response: In autumn 2023, NHS England announced work to develop and test a model of multi-agency working to support patients exposed to valproate. This model will operate as a ‘hub and spoke’ project in 2024 and is being run in conjunction with the Newcastle and Manchester NHS Foundation Trusts.

Epilepsy Action verdict: The government’s response to this recommendation has been slow and confused. The recommendation was initially accepted, but the government then stated they had no intention of setting up specialist centres for those adversely affected by medications taken during pregnancy.

While they have since established the pilot Fetal Exposure to Medicines Service (FEMS), progress would have been much quicker had the response to this recommendation been consistent from the start.

We welcome the establishment of the FEMS pilot in Newcastle and Manchester and would urge the government to ensure that the service is rolled out to all parts of the UK to ensure that patients exposed to valproate will have access to expert diagnosis, treatment plans and a range of physical, psychological, social and educational support.

Government response: “We accept this recommendation.

The MHRA – reflecting its corporate Delivery Plan 2021 to 2023, Putting patients first: a new era for our agency – has initiated a substantial programme of work to:

• improve how it listens and responds to patients and the public
• develop a more responsive system for reporting adverse incidents
• strengthen the evidence to support timely and robust decisions that protect patient safety

The MHRA is transforming organisational culture to ensure patient safety remains at its core.”

Epilepsy Action verdict: Some slight progress has been made to implement this recommendation.

Adverse event reporting

The Yellow Card scheme remains the way in which patients report serious suspected adverse reactions to a medicine, but there is a distinct lack of awareness of the scheme among the general public, which therefore limits the schemes effectiveness.

The MHRA’s Delivery Plan makes reference to the development of an updated adverse event reporting system, however, there has been no report on progress towards implementing this as a new system or integrated into existing arrangements.

Engaging with patients

The systems in place are not sufficient to communicate the risks to health professionals and women with epilepsy. A survey led by Epilepsy Action in collaboration with other epilepsy charities found that 33% of women taking carbamazepine, topiramate, pregabalin, phenytoin, or phenobarbital didn’t know they increase the risk of physical birth abnormalities if taken during pregnancy.

Since that report,safety measures have also been introduced for Topiramate, but other ASMs that have been identified as potentially posing a risk have not been addressed.

New regulations have been implemented around the prescription of sodium valproate, without engagement with patients or patient groups. These regulations are often introduced with little notice and have been the cause of distress and confusion for many people with epilepsy. Following any new announcement we see an increase in calls to our helpline, and leads to an increase in people with epilepsy contacting us seeking reassurance, further information and clarity.We would urge further commitment from MHRA to engage with patients and seek their views and experience priorto making decisions about changes to prescribing rules for valproate, and/ or other epilepsy medicines. This has not happened so far, and it is vitally important that this does change going forward.

We would also welcome clarity around how MHRA is monitoring the patient safety impact of the measures it has introduced. There are concerns from many patients about the impact increased regulations around valproate have had on their ability to access their medication, and therefore their seizure control. We seek guarantees from MHRA that they are ensuring that nobody has their epilepsy medication taken away against their will.

Raising Awareness of its role

There is still a general lack of awareness of MHRA, and its role and function. More work is needed to engage with members of the public to raise this awareness, particularly among patients, carers, and marginalised groups who may be disproportionately affected by regulatory decisions. The MHRA’s current communication and engagement strategies often fail to reach those most at risk or affected by medicine safety issues. To build public trust and improve patient safety, the MHRA must invest in accessible, inclusive communications, co-design its engagement with patient groups, and ensure that patients’ lived experiences inform all aspects of its regulatory work — from adverse event reporting to medical device oversight. This means moving beyond passive consultation to actively involving patients as partners in decision-making.

Government response: “We accept this recommendation.

We have already legislated for this through the Medicines and Medical Devices Act 2021, which creates a power for the Secretary of State for Health and Social Care to regulate for the establishment of a UK-wide medical device information system (MDIS).

Alongside developing regulations, over £11 million has been set aside for a package of work in 2021 to 2022 involving partners across the healthcare system to scope, test and cost options for MDIS and other medical devices patient safety workstreams, as well as complete a business case for a 5-year programme of work.”

Epilepsy Action verdict: We welcome the establishment of the Medicines and Pregnancy Registry and the fact that it now includes prescribing data for 12 different epilepsy medicines.

The Medicines and Pregnancy Registry will provide valuable information about the use, benefits, and risks of epilepsy medicines taken in pregnancy.

Government response: “We accept [the first part of] the recommendation in principle as we agree that doctors’ interests should be declared and publicly available. Furthermore, we believe this should be extended to all registered healthcare professionals.

We do not think that the GMC (or other regulator’s) register is the best place to hold this information. We will ensure there is a regulatory requirement that all registered healthcare professionals declare their interests, and that this information is published locally at employer level.

We accept in principle the need for stronger reporting in [the second part of] recommendation 8.

We support transparency of payments from industries, and we are exploring options to expand and reinforce current industry schemes, including making reporting mandatory through legislation.”

Epilepsy Action verdict: The expansion of the register of the GMC has not been implemented yet. The government consultation on proposals to disclosure of industry payments to the healthcare sector closed on 16 October 2023, but there has been no response from the government.

The almost two year wait since the consultation closed is unacceptable. Implementing this recommendation as a matter of urgency would ensure that patients are better informed and able to consider all the factors when making decisions regarding their treatment.

Government response: “The government has no plans to establish an independent taskforce to implement the report’s recommendations. A cross-system working group has already been set up, meeting regularly, to develop the government’s detailed response to the report.

“However, the government recognises the need for effective patient engagement both to build trust, and ensure effective implementation. I am pleased to announce today that we are establishing a Patient Reference Group, which is part of Baroness Cumberlege’s ninth recommendation. The Patient Reference Group will ensure that patient voices are heard as we move forward towards a full response to the report.”

Epilepsy Action verdict: Despite rejecting the idea of setting up a task force, the government has established a Patient Reference Group, which has met to discuss progress towards implementing the recommendations. However, the Patient Reference Group is only able to provide feedback on proposals, when in theory a task force could have had powers to actually implement the recommendations.

Given the lack of progress on many of the recommendations 5 years on from the publication of the Cumberlege Review, we would urge the government to reconsider their position on this matter and set up a task force to ensure that the Review’s recommendations are implemented in full.

Recommendation: An indicator on safe prescribing in pregnancy should be introduced for future iterations of the Quality and Outcomes Framework (QOF).

Epilepsy Action verdict: The QOF rewards GPs for the provision of quality care and helps to standardise improvements in the delivery of primary medical services throughout England. We were very disappointed when the initial QOF was retired in 2014.

We continue to believe that the QOF should be reinstated, and have raised this regularly with the Department of Health since the QOF was retired. Healthcare professionals should be encouraged and incentivised to discuss these risks with women and girls and reinstating the QOF would be the best way of achieving this, and ensuring that the existing evidence about other ASMs are also discussed with patients.

Recommendation: A clear process should be agreed to ensure women are able to get appropriate counselling related to their epilepsy treatment and contraceptive choices.

Epilepsy Action verdict: While basic pre-conception counselling is available in some areas, much more needs to be done to ensure that women with epilepsy are able to access tailored support as standard. This is to ensure that they have the necessary information to make an informed choice about their care and treatment during pregnancy.

We have consistently called for all women with epilepsy to receive pre-conception counselling and family planning advice tailored to their condition and needs. As mentioned in recommendation 5 of the Cumberlege report, specialist centres should be set up to provide comprehensive treatment, care and advice for those adversely affected by medications taken during pregnancy through which pre-conception counselling could be delivered.

Recommendation: Information should be collected to identify those already affected by exposure to valproate in utero to ensure they have access to diagnosis and support, and to plan service provision.

Epilepsy Action verdict: We understand that work is ongoing in individual trusts, but as many women were unaware of risks at the time they were taking valproate, it is difficult to identify all those who may have been affected.

Access to diagnosis and support is still not sufficient, especially without a redress scheme in place.

A more concerted effort is needed to identify all those affected by exposure to valproate. Sufficient support for those affected will not be achieved without a redress scheme and we would urge the government to establish such a scheme as a matter of urgency.

In addition, efforts should be made to identify those who have passed away to ensure that they, and their families, are not forgotten as part of this process.

Recommendation: A prospective registry should be established for all women on antiepileptic drugs who become pregnant, to include mandatory reporting of data relating to them and their child(ren) collated over lifetimes. This registry could potentially be expanded to collect data on paternal and transgenerational effects.

Epilepsy Action verdict: The Medicines and Pregnancy Registry has been established and has published reports providing data on the number of pregnancies exposed to valproate.

The Registry’s ongoing reports support the MHRA in monitoring the level of success of the valproate pregnancy prevention plan (PPP) and to enable the wider health and care system to further understand outcomes for women prescribed valproate during pregnancy and their children and consequently to improve patient care.

We urge the MHRA and NHS Digital to expand the registry to collect data on paternal and transgenerational effects, to measure whether there are any correlations between ASMs taken by fathers and adverse outcomes in pregnancies/children or transgenerational effects. By building this body of evidence we can ensure that all people taking epilepsy medicines have as much information as possible to make an informed decision about their treatment.

Recommendation: The relevant stakeholders should continue to work with patient groups to monitor and improve the PPP and to consider the next steps, which should include NHSE&I writing directly to all women and girls of childbearing potential, asking them to see their general practitioner or specialist.

Epilepsy Action verdict: The MHRA has not been meaningfully engaging with patient groups to monitor or improve the PPP or to consider the next steps. It is vital that MHRA works more meaningfully with patient groups as part of its regulatory role. To date, engagement has too often been superficial or tokenistic. Patient organisations have a deep understanding of the real-world impact of these policies and should play a crucial role in both ensuring that the PPP is implemented in a way that is both safe and person-centred, and monitoring and improving the PPP.

The MHRA wrote to all women and girls of childbearing potential.

While data from the Medicines and Pregnancy Registry shows that the number of pregnancies exposed to valproate have significantly decreased since the introduction of the PPP, little action has been taken to monitor the impact of reducing access to valproate. We would urge the MHRA to do more to monitor outcomes of those women and girls who have been moved from valproate and onto to different epilepsy medicine.

More needs to be done to ensure that the PPP and annual risk acknowledgement form are flexible enough to take individual circumstances into account. It is important that a balance is found between allowing women to make a choice about their treatment and care, while limiting the number of pregnancies exposed to sodium valproate, and other harmful epilepsy medicines.

Improvements to the PPP are needed, including the provision of guidance to clinicians outlining the circumstances in which there is an absence of risk of pregnancy. Currently there is no information for clinicians leading to different specialists making different determinations. Clear guidance would ensure that all women and girls are treated equally under the PPP.

Special consideration is also needed for parents or carers of women and girls with learning disabilities in relation to sodium valproate and the PPP, as well as how best to communicate the risks. Discussing the risks of pregnancy can be upsetting for these women and girls and their family or carers.

Recommendation: Clinicians should continue to follow guidance regarding prescribing of valproate and alternatives for all indications.

Epilepsy Action verdict: In the 5 years since the Cumberlege report was published, MHRA have introduced a number of new measures around the prescription of valproate. Data from the Medicines and Pregnancy Registry suggests that these measures have been effective in reducing prescriptions, and importantly, the number of pregnancies exposed to valproate.

As above, the QOF should be reinstated and healthcare professionals encouraged and incentivised to discuss these risks with women and girls.

In January 2021 the Commission on Human Medicines (CHM) published its review of the available safety data for epilepsy medicines use during pregnancy, which identified a number of epilepsy medications that also posed a risk of harm to the unborn child if taken during pregnancy. Clinicians should be advised of the need to discuss the risks of all epilepsy medications identified in the CHM review.

Recommendation: A system similar to the Pregnancy Prevention Programme (PPP) where teratogenicity is well-known or the effects are severe. Alternatively an acknowledgement of risk form should be attached to the prescribing and/or dispensing of all medication considered to have teratogenic potential or known to have a risk above that of the general population

Epilepsy Action verdict: So far the only other ASM to be made subject to a PPP is Topiramate. No other measures have been introduced for any other medicines

However, there is also some limited evidence of the teratogenic potential of Carbamazepine, Phenobarbital, Phenytoin and Pregabalin.

We would welcome further research into these epilepsy medicines, in addition to further measures to ensure that women and girls are made aware of the potential risks of taking these medications. Given the current limited evidence around these medicines, an acknowledgement of risk form would be preferable to additional PPPs. The risk acknowledgement forms for these medicines could then be updated as new evidence emerges. These forms would also provide guidance to professionals on what the risks are or may be, what the existing evidence for them is, and how to discuss them with patients. It would also provide evidence that these conversations have happened, and ensure that patients have been provided up-to-date information about the current evidence of any risks posed by their medication.

In addition, further research is needed into other epilepsy medicines to determine whether they are safe to use in pregnancy. Currently there are 10 epilepsy medicines (Brivaracetam; Clonazepam; Eslicarbazepine; Ethosuximide; Lacosamide; Perampanel; Primidone; Rufinamide; Tiagabine; Vigabatrin) for which there is not enough evidence to make any conclusions about their safety when used during pregnancy. Given the emerging evidence around other epilepsy medicines this lack of information is very concerning and creates a great deal of uncertainty for women and girls currently taking these medicines.

Conclusion

While some important progress has been made, there are far too many areas where we are still waiting for action and further response from the government. It is also deeply concerning that they have so far chosen not to respond to the specific recommendations on sodium valproate.

Most urgent is the need to establish a redress scheme for the 20,000 families that have been harmed by valproate. Some of these families have been facing these issues for 40 years. They have already waited too long for the support they need – they should not have to wait any longer.

More action is also needed to address the current lack of robust evidence around the safe use of other epilepsy medicines in pregnancy. It has been 4 years since the Commission for Human Medicines (CHM) reviewed the existing evidence of the risks associated with the most commonly prescribed anti-epileptic medications during pregnancy. Despite some limited evidence the risks of using Carbamazepine, Phenobarbital, Phenytoin and Pregabalin, during pregnancy, little has been done to build upon this. And as noted above, there are 10 other medicines whose safety is unknown. Since the CHM review, new epilepsy medicines, such as cenobamate, have also emerged and are being prescribed on the NHS.

Without further research, women and girls will not be given the information they need to make an informed choice about their treatment.