The Independent Medicines & Medical Devices Safety Review (The Cumberlege Review)
This article originally appeared in Issue 6 (September 2020).
“We have been astonished,” wrote the authors of the Cumberlege Report, “how the healthcare system – which includes the NHS, private providers, the regulators and professional bodies, manufacturers, and policymakers – is disjointed, siloed, unresponsive and defensive. It does not adequately recognise that patients are its sole purpose”.
Over two years Baroness Cumberlege and her small review team looked at three medical interventions: the pelvic mesh; sodium valproate (prescribed to treat epilepsy and bipolar disorder) and a hormone pregnancy test (HPT), Primodos. Each intervention caused, or was associated with, life-changing harm to tens of thousands of women and in the case of sodium valproate and Primodos, to their unborn children. Many lives were destroyed. The Review came after decades of battling to be heard.
The Review’s report is a shocking, dispiriting read. These women, or their children, suffered avoidable harm. That these interventions continued for decades unchecked, exposes serious flaws in the regulatory and complaints systems, in data collection processes, in obtaining informed consent, in applying the duty of candour and in managing conflicts of interests between drug companies, consultants, hospitals and even regulators.
These failures comprise the Review’s overarching findings and were common to each of the interventions. Another central theme is loss of the patient voice. Affected patients struggled to navigate a fragmented, confusing system for raising concerns. The women who managed to do so were simply not listened to. The response was defensive. They were ‘gas lighted’ – made to feel they were unstable, that their symptoms were all in their heads. They were told “these are women’s issues” or “it’s that time of life”. The report is not the first to highlight dismissive attitudes towards women’s health, (particularly where thought to relate to menstruation or the menopause), but it is certainly one of the starkest.
Patient safety, the report declares, must be given a higher priority. Innovation in medicine is a great thing but it has to be managed safely.
A vein of frustration runs through the text. Similar failures have occurred before. Systems were put in place to address them but in practice change is slow. For example, obtaining informed consent is fundamental to the safe working of a healthcare system. The 2015 landmark case of Montgomery v Lanarkshire Health Board made clear: consent needs to be framed around what information an individual patient requires. In response to the case, patient information leaflets proliferated, found the Review. These were often “bewildering”. Many of the women affected had not been informed of the risks and did not know what had been done to them. The Review team were “appalled”. And despite past public inquiries, there remains “a persistent culture of reluctance to speak out”.
Primodos was an oral HPT – in the form of a pill – containing both an oestrogen and a progestogen, used from the 1950s until it was withdrawn in 1978. If a women was not pregnant she would have a period-type bleed a few days after taking the HPT, if she did not bleed she was pregnant. Use of the HPT was associated with miscarriage, stillbirth, baby deaths, along with conditions including spina bifida, limb defects, deafness, blindness and mutism, congenital heart defects, intelligence disability, genito-urinary defects, dysmorphic facial features, digestive and bowel issues, skeletal problems, spinal issues, and seizures.
The first study to find a statistically significant association between HPT use and malformations (teratogenicity) was in 1967. Despite the existence of a risk-free alternative test, the drug was not withdrawn and continued to be prescribed. The regulator issued a warning in 1975 which proved ineffective. Women were not informed of the risks. In 1977 litigation was launched but discontinued due to concerns about proving causation in an environment where legally-aided claimants had difficulties in securing experts. The 2019 Expert Working Group (“EWG”) found that evidence did not support causation, but this conclusion, and the EWG’s process, have been heavily criticised by campaign groups.
Children with defects born to mothers who took Primodos require on-going care. The report also highlights improvements needed in EWG processes, around participation, transparency, perception of independence and declarations of interest.
Sodium valproate is used by about 27,000 women of child-bearing age in the UK, despite being a known teratogen. From the 1980s, data suggested an association with physical malformations, and later with neurodevelopmental problems now referred to as Foetal Valproate Spectrum Disorder (FVSD). Mothers of child sufferers reported feeling guilt and struggling to access services, particularly to support their children’s special educational needs.
The Review recommends specific actions to improve the safety of prescribing and to ensure better information and advice is given to women about their epilepsy treatment and contraceptive choices. Better data is also essential, and the report proposes a new system for collating data from those already affected (to ensure they are adequately supported) and from those on antiepileptic drugs who become pregnant.
The pelvic or vaginal mesh is a surgically inserted device, usually made of polypropylene, to relieve pelvic organ prolapse and urinary incontinence. Many women have found the procedure helpful. Many others found it ruined their lives. Still it was used, for decades, until 2018 at the outset of the Review, when the procedure was paused.
The report explains how historically, medical devices have been less regulated than medicines. The product was marketed, under an EU-wide regime, as being equivalent to other existing products but with little long-term testing of its effects. When the devices proved difficult to insert, their design was simplified (as opposed to ensuring surgeons doing so were sufficiently skilled).
When women reported pain (often excruciating, like having razors inside their bodies) and loss of mobility and sexual function, these were rarely reflected in the adverse event reports produced by manufacturers. The reports adopted a narrow definition of a product’s performance: if it relieved incontinence, it was a success. Since pain and problems during intercourse didn’t feature in formal evaluation of the device, doctors were unaware of these outcomes and many disbelieved patients who reported them. The women were thought to be exaggerating or hysterical and were brushed off. So, the report finds, “current data does not reflect complication rates”. Incredibly, given the scale of the complications, the Review found no medical consensus on how to remove problematic pelvic meshes or whether removal should be full or partial. The manufacturers must research and develop a “remedial strategy”, says the report, to address severe complications caused by their product.
The Cumberlege Review makes nine core recommendations and proposes further actions for improvement. A “fulsome apology” on behalf of the healthcare system is the first recommendation. This was delivered by the Health Secretary on 8 July 2020, the day of the report’s publication.
The remaining eight recommendations focus on care for those still suffering the effects of these disasters (including specialist centres to undertake complex remedial mesh surgery) and on better regulation to prevent future failures.
The report rejects the idea of further NHS re-organisation or a new regulatory body. What the system lacks and needs, it says, is a Patient Safety Commissioner. A “person of standing” answerable to Parliament who will listen to patients, advocate for them, monitor trends and demand action. An essential tool for the Commissioner will be good data. The system is currently “flying blind”, the Review found. No one knows, for example, how many women had pelvic mesh implants, who their surgeons were, what products were used or the outcome. Better recording must collate this type of information.
The report notes how little litigation seemed to do for the affected women. Some successful claims were made against individual doctors but no product liability cases succeeded, leaving tens of thousands without meaningful redress. In the immediate, the Review recommends that schemes be set up to meet the cost of additional care and support for those who experienced avoidable harm (and are eligible to claim), funded by a levy on manufacturers. These should be administered by a Redress Agency, which adopts a “no-blame”, “non-adversarial” approach.
Meanwhile, the Medicines and Healthcare Products Regulatory Agency (MHRA) needs “substantial revision” says the report, especially in relation to adverse event reporting and regulating devices. The movement of staff between the MHRA and the industry is a concern and the MHRA needs to engage patients much more in its work. Leaving the EU regulatory regime may be an opportunity to create a more transparent system with a publicly accessible database of adverse event reports.
To address potential or perceived conflicts of interest, the Review recommends expanding the General Medical Council (GMC) register to include financial and other links doctors have with manufacturers. Likewise, manufacturers should declare payments made to teaching hospitals, research institutions and individual clinicians as required in the US.
An Implementation Task Force is the Review’s final recommendation, to ensure the necessary changes are made. Many bodies within the healthcare system are urged to work better, in the interests of patients. Individual Trusts will need to strengthen their quality assurance systems to make sure clinicians follow NICE Guidance. Trusts must act on information which patients convey and address the persisting culture of defensiveness.
The report concludes by underlining the heavy responsibility on Government and the healthcare system to ensure that the Review’s advice is heeded. If it is not, the Review Chair warns, and another intervention causes damage on such a scale, they “will not and should not be forgiven”.