A SCANDAL WORSE THAN THALIDOMIDE
Our firm is currently acting for approximately 15 families whose children have been affected by exposure in utero to the common anti-epileptic drug sodium valproate (Epilim). The firm expects the first such case to come before the High Court this Autumn.
Despite political statements and HSE provided genetic testing, our clients continue to experience a dearth of supports.
Furthermore, despite such HSE genetic testing finding sodium valproate to be the cause of our clients injuries, liability remains in issue in all cases. This, of course, adds to the families distress.
This is further compounded by recent reports that women are still not being informed of the risk of taking epilepsy drug sodium valproate whilst pregnant.
Although the risks of taking valproate whilst pregnant have been known since its availability in Ireland in the 1970s, for decades Irish women have been prescribed the drug without any warning from their doctors.
A report by the HSE estimates that between 153 and 341 children will have experienced a major congenital malformation and up to 1,250 children will have experienced a neurodevelopmental delay from exposure to valproate between 1975 and 2015. 30-40% of children who are exposed to valproate whilst in the womb will have developmental disorders and approximately 10% will have congenital malformations, according to Epilepsy Ireland.
In a survey by Epilepsy Ireland in 2020, it found that one in three women are unaware that taking sodium valproate (Epilim) whilst pregnant can cause learning and development problems in children. One in six were unaware that use of the drug in pregnancy can cause birth defects.
Below is an article published in The Sunday Times in April 2022
The moment her newborn son Sebastian was handed to her, Catherine McNamara knew something was terribly wrong.
His tiny hands were deformed, unnaturally twisted and facing in the wrong direction. One was missing a thumb.
At first, she and her partner tried not to worry as their baby was taken off for x-rays and examinations. “We thought it was something they could fix,” she said.
But a few days later, the couple were devastated as doctors told them Sebastian’s deformities were permanent — and had been caused by the drug McNamara had been taking to control her epilepsy.
She burst into tears. “I just felt so guilty. All I could think was, what have I done to him?”
Like thousands of women, McNamara had been told her epilepsy medicine, sodium valproate, was safe to take during pregnancy. “They told me everything would be fine,” she said.
In fact, by the time her son was born in 2012, there had been multiple warnings over decades that the drug was unsafe for pregnant women.
Sodium valproate, which was given to women with epilepsy for decades without proper warnings, has caused autism, learning difficulties and physical deformities in up to 20,000 babies in Britain.
Yet despite a 2020 report that criticised the failure over four decades to inform women about the dangers, doctors are still not properly warning women of the risks. According to the latest data, published in March, sodium valproate was prescribed to 247 pregnant women between April 2018 and September 2021.
As a result, about six babies every month are being born in the UK having been exposed to the drug.
An investigation by The Sunday Times has found that the drug is still being handed out to women in plain packets with the information leaflets missing, or with stickers over the warnings.
The government is refusing to offer any compensation to those affected by sodium valproate, despite an independent review by Baroness Cumberlege concluding in 2020 that families should be given financial redress.
The former health secretary Jeremy Hunt says doctors should now be banned from prescribing the drug to pregnant women — and that the families affected by it must be properly compensated.
He has compared the case to the scandal of the anti-morning-sickness drug thalidomide, which caused deformities in thousands of babies after it was licensed in the UK in the 1950s.
Hunt said that while it was “never comfortable” for governments to acknowledge such injustices, the state had a moral duty to the families. “It’s time the British state faced up to its responsibilities,” he said. “Just as we eventually did to victims of the thalidomide scandal.
He added: “It beggars belief that after so many warnings this still hasn’t been sorted: this is a major risk to patient safety and ministers must order an immediate fix to prevent any more avoidable harm.”
Avoiding ‘fruitless anxiety’
When sodium valproate was introduced as a new epilepsy drug in the 1970s, the British medical community was still reeling from that very scandal — in which hundreds of babies were born severely deformed after pregnant women were given thalidomide.
The UK’s newly formed Committee on Safety of Medicines had been designated as the key decision-making body on new medicines.
Sebastian, 9, was born with a hand deformity caused by sodium valproate. His mother, Catherine McNamara, had been taking the drug to control her epilepsySebastian, 9, was born with a hand deformity caused by sodium valproate. His mother, Catherine McNamara, had been taking the drug to control her epilepsy
Sebastian, 9, was born with a hand deformity caused by sodium valproate. His mother, Catherine McNamara, had been taking the drug to control her epilepsy.
This committee — whose membership comprised some of the UK’s leading medics and was chaired by Sir Eric Scowen, professor of medicine at St Bartholomew’s Hospital in London — met to discuss sodium valproate on multiple occasions in 1972 and 1973.
They noted that the drug had shown enormous promise in controlling the terrible seizures suffered by patients, even for those whose epilepsy had proven resistant to other treatments.
Sodium valproate is still a safe and effective drug for sufferers of epilepsy, who should not stop taking it without first discussing this with their doctor.
However, the notes of the meeting show that the manufacturers, Sanofi, had raised to the committee that there were signs in animal tests that valproate could potentially be teratogenic — harmful to foetuses.
The committee concluded that the use of anti-seizure drugs such as sodium valproate was indeed “liable to produce” abnormalities. But they stated that “the risk appears to be low, and not sufficient to justify stopping the use” of the drug.
In a decision that would have disastrous consequences for thousands of families, the committee chose not to alert the public to the concerns that the drug could harm babies — concluding that since the evidence was not clear, doing so would risk causing “fruitless anxiety” to patients.
They specified that warnings should be provided to doctors, “but not on package inserts, so that there would be no danger of patients themselves seeing it”.
The committee’s decision not to warn women of the risks was probably “influenced by the paternalistic nature of society at the time”, believes Dr Rebecca Bromley, a paediatric neuropsychologist at the University of Manchester.
She believes the committee did not appear to consider the need for “women to have an informed say in their treatment”. Instead, the effect of the decision was to “leave patients fully in the dark about the risk that their medicine might carry”.
The committee licensed the drug for use in the UK and failed to order any surveillance or detailed studies on the outcomes for pregnant women taking it.
“What was lacking was the urgency to understand the risks more comprehensively,” Bromley said. “Complementary studies could have been established. They would have detected the risks sooner.”
Reports of abnormalities
In the early 1980s, reports started to appear of babies being born with abnormalities. One, published in August 1980 in the Journal of Paediatrics, told of a girl born with severe physical deformities who lived for just 19 days. Her mother had taken sodium valproate during pregnancy.
The following year, the case of a baby boy born with abnormalities to his feet, spine and brain was reported in the same journal. Again, the case was linked to sodium valproate.
The journal appealed for information about any other incidents linked to the drug. In response, a number of similar cases were reported by doctors.
“One report or even a few do not make conclusive evidence,” said Bromley. “But the sheer number and similarity of the symptoms reported was screaming that there was cause for concern.”
The medical authorities in the UK were slow to respond.
At that time, medical regulators relied on doctors reporting adverse effects of drugs in their patients. But in the case of drugs that harm babies, the effect was not seen in the patient but their child — so the doctor who initially prescribed the drug was often unaware, especially as there was often a time lag of years before the issue emerged. “The system was not set up to detect these risks quickly,” Bromley said.
In 1983, an article in the British Medical Journal examined four cases of babies born with deformities in which sodium valproate had been the only drug taken by the mother. The article said the findings “may call into question the wisdom” of prescribing sodium valproate as the preferred anti-seizure drug.
Sebastian was born in May 2012
This time, the concerns reached the floor of the House of Commons. But when the issue was raised by Labour MP Alan Williams in February 1983, his concerns were dismissed by then health minister Geoffrey Finsberg.
Finsberg assured MPs that the Committee on Safety of Medicines (CSM) had “concluded that there was no clear evidence” that sodium valproate was “more dangerous in this respect than other similar drugs”.
By the late 1980s, though, manufacturer Sanofi was receiving a growing number of reports of babies born with abnormalities.
A systematic review of evidence published by The Lancet also found an increased risk of spina bifida in children exposed to sodium valproate — although the authors bemoaned the lack of “high-quality evidence”.
The CSM finally acted on the concerns, asking Sanofi to write to all GPs and hospital doctors with a new warning sheet, setting out that sodium valproate could lead to birth defects.
However, the committee still stopped short of requiring doctors to tell women about the risks, with the danger of spina bifida not being included on patient safety leaflets until 1994. And still no detailed research into the effects of the drug was commissioned.
As a result, many doctors continued to prescribe the drug to pregnant women.
Janet Williams was one of them. At the time when she took sodium valproate while pregnant with her sons in 1989 and 1991, there were no warnings in the packets and no patient information leaflets. “Nobody said anything about risks,” she recalled. “In those days, you trusted your doctor.”
Both boys were born with disabilities.
Foetal valproate syndrome
It wasn’t until the mid-1990s that doctors started to recognise the problems affecting Williams’s two sons as “foetal valproate syndrome”.
The full spectrum of abnormalities seen as part of the syndrome was set out for the first time in a 1995 report in the Journal of Medical Genetics.
But while geneticists and paediatricians were becoming increasingly convinced of the problem, their concerns were not reaching the ears of the neurologists who were actually prescribing the drug, said Bromley.
Few of these doctors “would have been reading genetics journals”, she noted. As a result, the drugs continued to be handed out to pregnant women.
Patricia Alexander, from Canvey Island, Essex, was advised to continue taking a high dose of 2000mg a day throughout her pregnancy with her son Joseph in 2000 — and again in 2009, when she was expecting her daughter, Amélie.
During her medical appointments, she repeatedly asked if the drug was safe. Her concerns were brushed off by doctors and specialist nurses.
“I had no idea about valproate syndrome,” she said. “No one had ever mentioned it to me.”
Both Joseph and Amélie were born with physical disabilities, and both would go on to be diagnosed as autistic. Alexander only learnt about foetal valproate syndrome years after the children were born.
“The first I knew was when I saw a survey on Facebook,” she said. “It was heart-wrenching to read. Every single difficulty my children have was in that questionnaire and attributed to sodium valproate.”
Janet Williams, right, of Preston, has two sons, both damaged by the sodium valproate she took while pregnant. Emma Murphy, from Radcliffe near Manchester, has five children, all with disabilities Janet Williams, right, of Preston, has two sons, both damaged by the sodium valproate she took while pregnant. Emma Murphy, from Radcliffe near Manchester, has five children, all with disabilities
Janet Williams, right, of Preston, has two sons, both damaged by the sodium valproate she took while pregnant. Emma Murphy, from Radcliffe near Manchester, has five children, all with disabilities
To this day, her children are completely dependent on her and her husband. Amélie walks on crutches due to a twisted leg that may require surgery. Joseph is unable to stand or walk normally.
“Unless you live our lives, you don’t know how much effort goes into just getting through a day,” Alexander said. “It’s exhausting.”
A living nightmare
Evidence was mounting that sodium valproate was causing not just physical abnormalities but also neurological problems.
A major UK and US study confirmed in 2009 that the use of the drug in pregnancy could damage children’s IQ. The higher the dose, the more severe the damage.
Bromley, who was involved in this study, said it was a key moment. “People stopped asking us to prove that the risks were there and started asking about the level of risk.”
Patient information sheets were finally amended in 2010 to refer to the risks to cognitive development including autism.
By this time, families were starting to ask questions. More than 100 attempted to bring a lawsuit against Sanofi over the damage their children had suffered — but it collapsed just three weeks before the trial was due to start as legal aid was withdrawn.
Janet Williams, who was supporting the families bringing the case, was devastated. She and her husband were struggling with their two severely disabled sons, Lee and Philip.
“It was a living nightmare,” she said. The couple desperately needed financial help to cope with their sons. “We’ve never really known why the case collapsed.”
As part of the legal settlement to avoid having to pay costs, parents were made to sign an agreement to say they would not bring litigation again.
Even now, pregnant women continued to be given sodium valproate — among them Catherine McNamara.
She already had two children with severe learning disabilities. Before getting pregnant again in 2011, she had explicitly asked both her GP and consultant whether the drugs could have affected her other children, and whether she should stop taking them before trying for a third baby.
“I went to the GP and said, ‘I’ve got two children with quite severe learning difficulties and autism, is there any chance it could be to do with my tablets?’
“The GP said no. He told me to just keep taking the tablets, everything will be fine. My consultant said the same thing.”
Her son Sebastian was born with deformities to his arms in 2012.
‘We never got a choice’
Following the collapse of the legal case, Williams was determined to keep speaking out about how sodium valproate had affected her sons.
By now, her boys Lee and Philip, both with severe learning difficulties, were under the care of paediatricians and geneticists, who had told Williams for the first time that they believed the problems had been caused by her epilepsy drug.
“That was the first time we had ever heard that valproate could harm babies,” she said. It later emerged that doctors had secretly diagnosed Lee with foetal valproate syndrome as a baby — but had never told her about it.
If she had known, Williams might have been able to prevent her second son from suffering the same fate. “I was angry,” she said. “Why had no one ever warned us?”
After she was filmed for local television news in 2008, Williams was contacted by mother of five Emma Murphy, from Radcliffe, near Manchester, who had seen the report.
During a long late-night telephone call, the pair talked through what had happened to them. Like Williams, Murphy had taken sodium valproate during all five of her pregnancies — between 2009 and 2019 — after being told it was safe.
“At every appointment, me and my husband asked if valproate was safe,” Murphy remembered. “The response was always: it’s the best medication.”
All five of her children suffered disabilities. Her daughter Lauren, now 17, cannot walk without leg braces; her son Luke, 16, is so sensitive to noise that they cannot boil a kettle at home.
Together, the two mothers fought to uncover the truth about what had happened to their babies.
They travelled down to London on the train, went to the National Archives and demanded the minutes of the original CSM meetings at which sodium valproate had been approved in the 1970s.
When they found the key documents, Murphy recalled: “I just took a sudden breath and screamed. I couldn’t believe it. I was in utter shock.”
The documents revealed that “right from day one, the regulators were aware there was a possibility babies could be harmed”, Williams remembered.
“And this was just after thalidomide. Women were never given an informed choice, right from day one.”
The pair fought to raise awareness of valproate and the harm it was doing. But it was not until 2017 that they were invited by the then health secretary Jeremy Hunt to prepare a case for financial redress for families, helped by the barrister Michael Mansfield QC.
In his summary, Mansfield concluded: “The scandalous reality of the original decision of the CSM is that since 1973 thousands of women have taken sodium valproate during pregnancy and unwittingly exposed their children to foetal valproate syndrome in circumstances where they could have chosen not to.”
He noted that there were “many similarities between the sodium valproate scandal and the thalidomide scandal” and that there was “no good reason” why the government should not adopt the same response as it did to thalidomide in 2012, providing millions of pounds for ongoing financial support.
The government, though, refused his call for compensation.
Instead, Baroness Cumberlege, a former health minister, was asked to carry out an inquiry into sodium valproate. The inquiry also examined the use of vaginal mesh and the hormone pregnancy test Primodos.
Announcing the review in 2018, Hunt said the inquiry was necessary into all three issues because in each case the healthcare system had failed to respond to patients’ concerns fast enough.
“We must acknowledge that the response to these issues from those in positions of authority has not always been good enough,” he said. “Sometimes the reaction has felt overly focused on defending the status quo rather than addressing the needs of patients.”
The resulting report, which was finally published in July 2020, concluded that the government had an “ethical responsibility” to provide financial help to families to cover the costs of care, and detailed how a “disjointed, siloed, unresponsive and defensive” healthcare system had for two decades failed to fully appreciate or act on the harmful effects of sodium valproate, and had dismissed women’s experiences and complaints.
The blank packaging used for sodium valproateThe blank packaging used for sodium valproate
The blank packaging used for sodium valproate
Still, the government refused to compensate the families.
In July 2020, Nadine Dorries, then patient safety minister, offered “an unreserved apology” to families and said she was left “shocked but incredibly angry” at reading the “harrowing” report. But she stopped short of offering any financial redress.
“A decent society has a duty to help people who are suffering so much,” said Cumberlege. “Such a scheme need not be a blank cheque; a comparatively modest sum would provide the support that these families so desperately need. I hope the government will do the right thing and act now.”
The French government has already established a dedicated compensation fund for victims. Sanofi is facing a class-action lawsuit in France, where more than 30,000 children are thought to have been damaged since sodium valproate was licensed there in 1967.
In January, a court ruled the company “was at fault because it failed to meet the obligation for vigilance and the obligation to inform”.
Sanofi says it has met all its obligations in the UK, where between 9,000 and 20,000 children may have been harmed by sodium valproate, scores more than were left disabled by thalidomide in the 1960s. A spokeswoman expressed “sympathy for any person harmed as a result of exposure to valproate during pregnancy and for members of their families” but added: “Sanofi has complied fully with its regulatory obligations in relation to valproate, including the provision of product information to healthcare professionals and to patients . . . we do not believe that there is any basis for the payment of compensation.”
Still no warnings
Patricia Alexander holds in her hands a plain packet. Inside are two blister packs containing sodium valproate.
This pack was given to her in January of this year. It has no patient safety information leaflet inside.
“Sometimes you just get a white box,” she said. “They are supposed to put the patient information leaflet inside and a card that warns you of the risks, but they don’t.
“The fact I am getting the boxes like this, because they have split the dose, means someone else is as well.”
Perhaps the most damning finding of Cumberlege’s report was her warning that hundreds of women were still taking sodium valproate with no knowledge of the risks to their unborn babies.
Evidence suggests that this still continues to this day — with the drug being handed to pregnant women without proper warnings.
The pack given to Alexander in January states on the front that if you are pregnant or plan to become pregnant, you must speak to your doctor about taking the medication and read the leaflet for more details.
“But there is no leaflet,” she said. “There is nothing in the box but 22 tablets. It makes me so angry.”
After she was given them, Alexander took photographs of the boxes and shared them online.
Other women did the same. Some had received the drugs in plain boxes. Others showed boxes with pharmacy labels stuck over the pregnancy warnings.
The matter of the drugs still being handed out in plain packaging, without the appropriate warnings, has been acknowledged by the Department of Health and Social Care.
It has admitted that “evidence continues to emerge suggesting many women remain unaware of the significant risks posed to their unborn baby should they fall pregnant while taking sodium valproate”.
Emma Murphy with her daughter LaurenEmma Murphy with her daughter Lauren
Emma Murphy with her daughter Lauren
ANTHONY DEVLIN FOR THE SUNDAY TIMES
It launched a consultation in November on proposals to ensure sodium valproate was always dispensed in the original manufacturer’s packaging “to support increased patient safety” — but the government has yet to respond.
An NHS England spokesman said it had established an expert group to help reduce by 50 per cent next year the use of sodium valproate by women who can get pregnant, and had written to all women and girls aged 12 to 55 in England who take the medication to remind them of risks.
But the medicines regulator has admitted warnings are still not getting through.
Dr Alison Cave, chief safety officer for the Medicines and Healthcare products Regulatory Agency (MHRA) said work was ongoing on safer use of sodium valproate and to minimise prescribing.
She said the MHRA was now working to ensure the drug was dispensed in the original packaging with the safety information inside.
“If there are examples where this information has not been provided, we would investigate this,” she said.
She added that the drug “should not be taken by any individual of child-bearing potential unless they have a pregnancy prevention programme in place, which includes use of effective contraception”.
She also said that women on sodium valproate were now required to sign annual risk-acknowledgement forms together with their healthcare professional “as their circumstances regarding the risk of pregnancy may change”. Patients who spoke to The Sunday Times disputed whether these measures were in place across the board.
Fears for the future
Since sodium valproate was first licensed for use in 1973, as many as 20,000 children may have been affected by it.
Many of those children will never live independently and will need full-time care for the rest of their lives.
Williams, now 57, lives with her husband Steve and her two boys Lee, 32, and Philip, 31. Both have disabilities caused by the drug, but Philip is the worst affected.
“He could never live independently,” said Williams. “And I am terrified we’re not going to be here for ever to do things for them.”
Murphy’s daughter Lauren, 16, cannot walk without splints. She has had to wait weeks to get replacements on the NHS.
“If parents had financial support we could buy them sooner,” she said. “And that’s just one case. We have thousands of children like that with valproate syndrome.”
For McNamara, 45, from Hull, life with three children harmed by sodium valproate is a daily struggle.
Alexander, 20, Sophia, 16, and Sebastian, 10, all have physical problems, autism and learning difficulties. Sophia had major surgery in 2019 to correct the curvature of her spine but couldn’t get a wheelchair from the NHS. Her mother had to buy one secondhand.
McNamara said the financial impact has been crippling. “I’m not able to invest in myself, a career. I can’t buy a house. Just to meet everyday expenses is difficult because I can’t go out and get a job.
“I take everything a day at a time. If you think too far down the line it really gets to you.”
After Sebastian’s birth, McNamara went on to have a healthy child after changing onto a different epilepsy drug, Keppra.
Although for some patients only sodium valproate will fully control their seizures, there are alternative anticonvulsant drugs available, and some women find they are able to change their treatment.
“If I’d known now that alternatives were out there, I’d have changed over without a second thought,” she said.
Alternative anticonvulsant drugs had never been offered to her until her children were diagnosed with foetal valproate syndrome, she says. “Nobody thought to mention it.”
The Department of Health and Social Care said: “Patient safety is a priority and we take all reports and inquiries on this matter extremely seriously.
“As set out in our response, we have accepted the majority of the recommendations in Baroness Cumberlege’s report. We want to improve the future safety of medicines and medical devices – ensuring they are used in line with the latest evidence of best practice — and there are wider forms of redress available for those who need it.”
Shaun Lintern, Health Editor
16th April 2022, The Sunday Times