The review announced last month will consider how the UK health system responds to reports from patients about side effects from three NHS treatments following patient-led campaigns:
- Primodos – a hormone pregnancy test that was used in the UK until 1978
- Sodium valproate – a medicinal product used to treat epilepsy and bipolar disorder
- Vaginal meshes – medical devices used for pelvic organ prolapse.
The review, which will be led by Baroness Julia Cumberledge, will consider whether any further action is necessary relating to the complaints around the three treatments; the processes followed by the NHS and regulators when a patient reports a problem; and how to improve communication between the different groups involved.
Primodos and hormone pregancy tests
Primodos was some time ago the most widely used hormone pregnancy test (HPT) in the UK and involved patients taking synthetic versions of progesterone (norethisterone acetate) and oestrogen (ethinylestradiol) orally. Blood would then be taken to determine whether the patient was pregnant. Primodos was also used to treat menstrual disorders.
A number of studies between the 1950s and 1978 were published investigating possible links between HPTs and congenital abnormalities. According to the recent Report of the UK Commission on Human Medicines' Expert Working Group on Hormone Pregnancy Tests, there was never any reliable evidence that HPTs were unsafe, but precautionary measures were taken to restrict the use of HTPs to disorders of menstruation and to prevent their use in women who were pregnant. However, these measures were not always adhered to.
A conclusion of the Report was that the available adverse event reporting data had many limitations but did not support a causal association between the use of HTPs (including Primodos) during pregnancy and congenital abnormalities. The findings of the Report have been subject to criticism from campaigners and some Members of Parliament.
Valproate has been authorised nationally within the EU for the treatment of epilepsy, bipolar disorder and, in some countries, the prevention of migraines. It is known that valproate is associated with a risk of malformations and developmental problems in babies exposed to the medicine while in the womb.
On 8 March 2017, the French regulator (ANSM1 ) notified the Pharmacovigilance Risk Assessment Committee (PRAC) of a referral under Article 31 of the Medicinal Products Directive (Directive 2001/83/EC)2 concerning "all medical products containing substances relating to valproate". In particular, ANSM asked PRAC to consider whether:
- There is a need to contraindicate valproate and related substances during pregnancy and in women of childbearing potential with no effective contraception in the treatment of manic episodes of bipolar disorder; and
- In light of a review of the effectiveness of the current risk minimisation measures across all indications, additional risk measures should be considered for valproate containing products and whether the marketing authorisations of these products should be maintained, varied, suspended or revoked.
The referral was made following concerns by the French regulator that recommended measures following an earlier review were insufficient.
On 8 February 2018, PRAC recommended that new measures should be put in place to avoid valproate exposure in pregnancy. As valproate is authorised at a national level, the PRAC recommendation will be sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh).3
Surgical meshes are medical devices that been used for a number of years to repair abdominal hernias, stress urinary incontinence, female pelvic organ prolapse and colorectal functional disorders. The use of such meshes has been associated with certain complications.
In 2014, the MHRA4 undertook a review of the evidence on vaginal mesh implants at the request of England's Chief Medical Officer. The review concluded that the benefits of the use of the devices outweighed the risks, so there was no justification for the MHRA to take action to remove vaginal mesh implants from use in UK hospitals.
A further report was published the next year by European Commission Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR). That report concluded that the clinical outcome following mesh implantation was influenced by a number of factors including material properties, product design, mesh size, route of implantation, patient characteristics, associated recommended procedures and the surgeon's experience. It also recommended certain limitations on the use of meshes the treatment of pelvic organ prolapse and the introduction of a certification system for surgeons.
The risks of using transvaginal mesh implants were reviewed again in a Scottish Independent Review, which published its report in March 2017. That also made a number of recommendations including that transvaginal mesh procedures should not be routinely offered to women with pelvic organ prolapse. The recommendations were accepted by Scotland's Chief Medical Officer.
In December 2017, the UK National Institute for Health and Care Excellence (NICE) updated its recommendations, advising that transvaginal mesh repair of anterior or posterior vaginal wall prolapse should only be used in the context of research.
Few details are known about the Government's review, but it is hoped that its findings will contribute to improved patient safety and healthcare practices.
The final outcome of the Article 31 referral will impact the indicated use of valproate across the EEA irrespective of the outcome of the Government's review. Additionally, the new Medical Devices Regulation (Regulation (EU) 2017/745) classifies surgical meshes as Class III medical devices, thus bearing the highest level of pre- and post-market scrutiny.