” This document contains the legal and moral arguments for a Public Inquiry into medicine and devices regulation to focus on valproate as a case study.
The history of the licensing and regulation of valproate is particularly enlightening and highlights that we as patients were not informed of the risks associated with valproate and neither were many of our Doctors. “
The Scope of this Submission
This submission is made on behalf of the Organisation for Anti-Convulsant Syndrome (known as OACs), the Foetal Anti-Convulsant Network (known as #FACSaware) and the individuals and families that both groups represent.
An outline of the essential work undertaken by these groups is provided below.
This submission is made to Baroness Cumberlege in her role as chair of the Government ordered Review announced by the Secretary of State for Health, Jeremy Hunt, on 21 February 2018. The purpose of this Review is to consider – in the context of medicinal products/devices identified as, Primodos, Sodium Valproate and Vaginal Mesh:
- ‘Firstly, the robustness and speed of the processes followed by the relevant authorities and clinical bodies to ensure that appropriate processes were followed when safety concerns were raised;
- Secondly, whether the regulators and NHS bodies did enough to engage with those affected to ensure their concerns were escalated and acted upon;
- Thirdly, whether there has been sufficient co-ordination between relevant bodies and the groups raising concerns; and
- Fourthly, whether we need an independent system to decide what further action may be required either in these cases or in the future’.
Mr Hunt explained; ‘This is because one of the judgments to be made is whether, when there has been widespread harm, there needs to be a fuller, or even statutory, public inquiry. Baroness Cumberlege will make recommendations on the right process to make sure that justice is done and to maintain public confidence that such decisions have been taken fairly’.
This submission relates to Sodium Valproate. It aims to help Baroness Cumberlege to consider these focal issues as they relate to Sodium Valproate.
The Purpose of this Submission
It is now well established by clinical researchers, in medical literature and across the regulatory community that Sodium Valproate is a teratogen; and that children exposed to this drug in utero suffer an increased risk of physical, developmental and neurological injuries. That cluster of injuries is known as ‘Foetal Valproate Syndrome’ (FVS).
With adequate warnings directed at both the users of Sodium Valproate preparations and their treating clinicians, FVS was, and is, an almost entirely avoidable injury. Yet, as at the date of this submission, as many as 20,000 individuals in the UK have been diagnosed with (or may suffer from) FVS.
In our submission the persistence of FVS as a diagnosis in the UK, and the number of individuals affected, is evidence of a long history of regulatory and legal failure in the prescription of Sodium Valproate as an anticonvulsant in the UK.
Those affected by FVS continue to pay the highest price for that failure:
‘I am mourning my child now and will be mourning the death of her when she’s gone, this is the result of Valproate, no parent wants to see their child slowly die in front of them’
They do so without any acknowledgment on the part of the manufacturer or regulator of the role that they have played in creating and perpetuating the incidence of FVS in the UK; and crucially they do so without compensation.
Against that backdrop, this submission sets out; the legal case for a Public Inquiry into the regulatory and legal failings exposed by FVS and describes both the urgent need, and moral imperative, for compensation to be paid to all those affected by FVS in the UK.
To achieve that purpose this submission is divided into 3 chapters:
- Chapter 1; provides the background on the clinical history and impact of Sodium Valproate in the UK;
- Chapter 2; sets out the legal case for a Public Inquiry and is focussed upon dealing with the first three issues raised by Mr Hunt in his announcement on 21st February 2018: These are the Governmental, regulatory and legal failings that have resulted in FVS and have necessitated the 40-year old campaign for justice led by groups such as OACS Charity and FACSaware.
- Chapter 3; sets out the moral imperative for the creation of a Compensation Fund, identifying the clinical and psychological needs of those affected by FVS and possible mechanisms through which such compensation could be awarded.
- Sodium Valproate medicines are used to treat various conditions such as epilepsy, the manic phase of bipolar disorders (since 2009) and severe migraines (this application is off label use in some EU countries).
- In the UK the primary use of Sodium Valproate is, and has always been, in relation to epilepsy as an anticonvulsant (AED).
- There is little doubt that Sodium Valproate is an effective medication in treating patients at risk of epilepsy associated convulsions.
- Sodium Valproate is marketed internationally under a range of brand names. In the UK, Epilim is by far the most dominant Sodium Valproate preparation available.
- Epilim was first licensed for usage in the UK in 1973. The company responsible for manufacturing and marketing the drug in the UK is now known as Sanofi.
- It is now accepted across the clinical and regulatory community by, for example, the National Institute for Health and Clinical Excellence (NICE), the MHRA and European Medicines Agency (EMA) that Sodium Valproate is a teratogen and that wherever possible prescription should be avoided in female patients of childbearing age.
- The congenital birth defects associated with in utero exposure to Sodium Valproate include:
- Neural tube defects (NTDs), such as spina bifida
- Cleft lip and palate
- Facial and skull malformations
- Heart, kidney, urinary tract and sexual organ malformations
- Limb defects
- Developmental delay
- Autism Spectrum Disorders (ASDs)
- Attention Deficit Hyperactivity Disorder
- Ear malformations and auditory processing
- Skeletal malformation
- Arthritis in older children
- Effects on the endocrine system
- Sexual identity problems (which occur due to a mismatch between genital development and neural / sexual identity development).
- Psychomotor issues.
- Withdrawal symptoms – associated with prenatal Sodium Valproate exposure.
It is important to understand that this list is not exhaustive.
- When these congenital abnormalities, either singularly or in combination, are identified in children exposed to Sodium Valproate in utero they are diagnostic signifiers of FVS.
- The controversy surrounding Sodium Valproate is focused upon the teratogenic potential of the drug and the historic failure of the regulator and manufacturer to communicate that potential to clinicians and patients.
- It is submitted that by the early 1980s the regulator/manufacturer was in possession of sufficient information to conclude that Sodium Valproate was a teratogen which increased the risk of congenital abnormalities above the risks associated with epilepsy in general or where alternative AEDs were used.
- However, this information was not communicated directly to patients until as late as 2005; whilst, in our submission, appropriate care pathways for women of child-bearing age using Sodium Valproate were not instituted by the regulator/manufacturer until as late as 2016.
- That failure of the regulator/manufacturer constituted a dereliction of their statutory duties under the Medicines Act 1968, and successive legislation, to safeguard patients and warn of the adverse risks associated with medications.
- That failure also created a fundamental ‘Information Gap’ between regulator/manufacturer-clinician/patient out of which the tragedy of FVS has developed.
- An info-graphic describing this ‘Information Gap’ is provided at Appendix B and in Chapter 2 of this submission. The case for a Public Inquiry into medical product regulation in the UK is made with reference to the creation and maintenance of this ‘Information Gap’ which is exposed through the history of FVS in the UK.
- Those affected by FVS and their families have complex care needs and are in the unusual position of having to cope with children with often profound disabilities whilst dealing with the fact of their own epileptic and or mental health condition.
- For many of the mothers with epilepsy who are caring for children affected by FVS, stress is a trigger for their epileptic convulsions; the fact that they have been unheard and uncompensated for so long, despite their persistent campaigning, has often exacerbated their own clinical condition – this has added injury to injury.
- We describe, in Section 15, the Double Disability which the mothers of FVS children experience; the fact of their own epilepsy in addition to the problems experienced by their children with FVS, a condition brought about by the Epilim which has enabled them to live normal lives. This imposes a significantly greater burden on these women than would be the case if they did not suffer from epilepsy.
- Setting aside the emotional and psychological costs; the physical care needs of those affected by FVS place significant financial demands on the individual families affected and upon the NHS and/or Local Authority, who have been left to shoulder the significant cost burden associated with FVS.
- Sanofi, the manufacturer responsible for Sodium Valproate, has made very significant profits as a result of its marketing of Sodium Valproate in the UK without shouldering any of the consequential costs of FVS injuries.
- Litigation initiated against Sanofi on behalf of those affected by FVS and their families was discontinued when the Legal Aid Agency decided to withdraw legal aid funding in 2010, three weeks before Trial: Consequently, FVS sufferers have been denied access not only to compensation but also the opportunity to bring the fact of the manufacturer’s and regulator’s failures into the public domain.
- This contrasts with the experience of FVS sufferers in other jurisdictions.
- In 2016 the French Government instituted payments to FVS sufferers through a centrally constituted Compensation Fund.
- The recent reparative actions of the French Government in respect of FVS, contrast with the historic inaction of successive UK Governments: This contrast is noteworthy given that both jurisdictions have had to deal with:
- the same drug (Sodium Valproate)
- the same injuries (FVS)
- the same manufacturer (Sanofi); within
- the same legislative framework- by virtue of the European wide Product Liability Directive.
- The scale of the task of compensating UK FVS sufferers is hard to estimate; however, the moral imperative to facilitate such compensation is abundantly clear:
‘I can tell you from my experience of 32 years that there has never been enough support/facilities within the community to cover the needs of my daughter or any other person with learning difficulties/special needs or disabilities. There has been a continuous lack of understanding of the complexities of FVS’
- In summary, this submission seeks the following outcomes:
- A compensation and care package for all those affected by FVS;
- A Judge led Public Inquiry into the regulation and licensing of medical products within the UK, focussing upon FVS as a case study; and
- Scrutiny of how consumers can be better safeguarded and, if necessary, compensated, in a revised regulatory framework post-Brexit.
Download the whole document via FACSaware group on Facebook.