Primodos: The next steps towards Justice

Primodos: Sharon Hartles critically examines the journey so far towards the implementation of the remaining eight recommendations set out in the landmark publication of the Medicines and Medical Devices Safety Review First Do No Harm report in July 2020.

Sharon Hartles was awarded an MA in Crime and Justice (with distinction) from the Open University in December 2019 and is a member of the British Society of Criminology (BSC). She has an interest in crimes of the powerful, including state and state-corporate crime. Sharon draws upon a zemiological approach to evidence the ways in which crime and harm are produced and interwoven into society via socio-economic inequalities.

Wednesday 8th July 2020, marked the publication of the final report by the Independent Medicines and Medical Devices Safety Review, which was commissioned to examine the harmful effects of three treatments: Primodos, an oral hormone pregnancy test that caused birth defects;  sodium valproate , an epilepsy drug that also causes birth defects, and surgical mesh, a treatment for incontinence that causes chronic debilitating pain. Primodos was the most widely prescribed ‘hormone pregnancy test’ in the UK (and around the world) in the 1960s and 1970s until it was taken off the market in 1978.  First Do No Harm found that avoidable harm was caused because the UK Government and the Healthcare system failed in their duty to protect patients and regulate Primodos.

For the Primodos-affected members of the Association for Children Damaged by Hormone Pregnancy Tests, a lobby group, the findings and recommendations offered recognition ‘that hundreds of families have been wronged.’ Recommendation 1 of First Do No Harm was fulfilled when Matt Hancock apologised for the avoidable harm caused to those who suffered. However, after this welcomed and prompt first step towards justice, the next steps – the implementation of the remaining eight recommendations – have been fraught with resistance. 

Baroness Julia Cumberlege, a life peer who chaired the Independent Medicines and Medical Devices Safety Review, explicitly championed the need for the recommendations set out in First Do No Harm to be implemented with determination and urgency. Despite this, it has now been more than three months since the report was published, which may not seem like much time within the political agenda, and given the preoccupations with Covid and Brexit, but England is lagging behind Scotland. At a 9th July 2020, press conference, Julia Cumberlege raised concerns about the importance of implementing the report’s recommendations and the significance of not leaving it to “sit on a shelf and gather dust”. 

Yet, two months later, amid rumours the report was going to be buried, during a Parliamentary debate which took place on 2nd September 2020, the Baroness requested assurances from Ministers that the recommendations would be implemented. On the same date, MP and chair of the All-Party Parliamentary Group on Hormone Pregnancy Tests, Yasmin Qureshi, took a different approach. Namely, she accused Government Ministers of hiding behind irrelevant “legal action, which has no bearing on this reports findings” to ignore their duty to implement First Do No Harm recommendations a point which she had previously voiced in a letter to Matt Hancock on 15th July 2020.

To its credit the Scottish Government has led the way; and on 1st September 2020, First Scottish Minister Nicola Sturgeon confirmed that Holyrood had accepted, in full, the recommendations of Baroness Cumberlege and would be appointing a Scottish Patient Safety Commissioner, “the emphasis of this new role is on the patient voice within the safety system.”  Moreover, on 13th September 2020, Andrew Davies, Shadow Minister for Health announced that a Welsh Conservative-led government would appoint ‘an independent patient safety commissioner in Wales.’ Currently, First Minister of Wales and the Welsh Labour-led government Mark Drakeford has not made any announcements regarding intentions towards the appointment of an Independent Patient Safety Commissioner.  

The Independent Medicines and Medical Devices Safety Review findings have had wider reaching ramifications. Primodos, a drug marketed by the West German pharmaceutical company Schering AG, was marketed in West Germany until 1981 as Duogynon. On 16th September 2020 the German Federal Ministry of Health announced it would be launching a review into whether or not the relationship between the regulator then the Federal Health Office today known as the Federal Institute for Drugs and Medical Devices  and the manufacturer then Schering AG, now Bayer AG led to ‘the drug remaining on the market despite concerns about its safety.’ 

In an article by Jason Farrell, Home Editor at Sky News, published on 19th September 2020, he noted ‘The German government has been reluctant to look into the issue and campaigners in Germany were relying on a breakthrough in the UK. That came after an independent review in Britain found in July that government health regulators had failed patients and that Primodos was responsible for “avoidable harm”.’ Although Jens Spahn German Federal Minster for Health, confirmed a research project into possible collusions between the German regulatory authority and the manufacturer; he also made it clear that “all the known findings and the scientific evidence do not currently support a causal link” between the hormone pregnancy test and birth defects.

Marie Lyon, chair of the Association for Children Damaged by Hormone Pregnancy Tests, met with the German Health Committee and MPs in March 2019 to present analyses from Oxford University scientists Carl Heneghan and Jeffrey Aronson. Based on the research conclusions she discussed a possible review of Primodos and Duogynon and its association with ‘increased risks of congenital malformations.’ The subsequent pressure from German politicians calling for a review, together with First Do No Harm findings played an instrumental part in sparking the German investigation into the Duogynon scandal. For Marie Lyon, who has been working with the Duogynon Network, an association for members affected by Duogynon, since 2012, the announcement came as “a huge step forward for the German campaign group and one we thought we would never see happen”.

Back in the UK, in a bid to ensure that First Do No Harm is not ignored, six leaders of political parties: Sir Ed Davey, Ian Blackford, Sir Jeffrey Donaldson, Caroline Lucas, Liz Saville-Roberts and Colum Eastwood signed a joint letter to Prime Minister Boris Johnson on 16th October 2020 urging him to ‘instruct the Department of Health to implement the findings of the Cumberlege Review’. According to the All-Party Parliamentary Group on Hormone Pregnancy Tests on 28th October 2020, Sir Keir Starmer added his signature of support, a notable action, because all seven opposition party leaders have presented a united front in calling on Boris Johnson to implement the Independent Medicines and Medical Devices Safety Review recommendations “in full and without delay.”

The UK government failed in its duty to regulate Primodos. The health care system failed in its duty to protect patients.  These failures resulted in avoidable harms spanning decades. For Primodos survivors these alleged life changing harms include: cardiac malformations, musculoskeletal, neurological, neurogenetical malformations, miscarriage and stillbirth. However, it was not the role of the Independent Medicines and Medical Devices Safety Review to determine whether or not there was ‘a causal association between HPT use and physical malformations’. Therefore the review findings have not laid to rest scientific debate around the contested harmful nature of this synthetic sex hormone. And so there are still open questions regarding claims about the effects caused.

What is significant, is that Recommendation 4 of First Do No Harm states ‘The state and manufacturers have a moral responsibility to provide ex gratia payments to those who have experienced avoidable damage from the interventions we have reviewed.’  First Do No Harm may not have determined a causal association but recommendation 4 suggests that the Independent Medicines and Medical Devices Safety Review findings are a long way from establishing harmlessness.

Now is not the time for the Government to unnecessarily prolong further suffering. It is time for these survivors of Primodos (and of sodium valproate and surgical mesh) to get the recognition and justice they so rightly deserve. In line with Recommendation 2, the appointment of an Independent Patient Safety Commissioner who will champion the patients’ voices and perspectives is long overdue. Furthermore, in accordance with Recommendation 9, action must be taken immediately to set up a task force in order to schedule a timetable for the implementation of the remaining recommendations as set out on 8th July 2020 by First Do No Harm.

To find out more about the Association for Children Damaged by Hormone Pregnancy Tests (ACDHPT) campaign and keep up to date with news, visit primodos.org. In addition, there are a number of ways you can support the campaign:

This article was originally published by the Harm & Evidence Research Collaborative on November 10, 2020 at:

http://www.open.ac.uk/researchcentres/herc/blog/primodos-next-steps-towards-justice

Contact

Sharon Hartles   

Email: sh28739@ou.ac.uk

Twitter: @shartles1

Images: Courtesy of author and CC BY-SA 3.0 Attribution: Alpha Stock Images – http://alphastockimages.com/

Primodos: The first step towards Justice

Primodos: Sharon Hartles reflects upon the significant impacts of avoidable harms that have been perpetuated for decades through a culture of denial and an absence of state and corporate pharmaceutical accountability.

Sharon Hartles (002)Sharon Hartles was awarded an MA in Crime and Justice (with distinction) from the Open University in December 2019 and is a member of the British Society of Criminology (BSC). She has an interest in crimes of the powerful, including state and state-corporate crime. Sharon draws upon a zemiological approach to evidence the ways in which crime and harm are produced and interwoven into society via socio-economic inequalities.

Primodos was the most widely used hormone pregnancy test prescribed to women in the UK. During 1958 to 1970 Primodos was marketed as a hormone pregnancy test and for the treatment of secondary amenorrhea. However, this was changed to just the treatment of secondary amenorrhea from 1970 to 1978, at which stage Primodos was withdrawn from the UK market. When Primodos was placed on the UK market in 1958 there was no centralised structured pharmaceutical regulation. In other words, no licence was required, no specific safety test was needed and there was no general consumer protection legislation.

In 1978, the Association for Children Damaged by Hormone Pregnancy Tests, was set up in the UK to represent families who suffered congenital abnormalities, stillbirths and miscarriages, allegedly due to taking the oral hormone pregnancy test Primodos. Decades of fighting for justice to uncover the truth about the failures of past Government Health Regulatory Authorities led to a review being commissioned in February 2018, by Jeremy Hunt, the then, Secretary of State.

The announcement in the House of Commons was for a review into how the health system responds to reports about harmful side effects from medicines. This stemmed from patient-led activist campaigns on the use of: hormone pregnancy test Primodos, sodium valproate and surgical mesh. Jeremy Hunt stated “patients and their families have had to spend too much time and energy campaigning for answers in a way that has added insult to injury for many.”

Two and a half years after this review was commissioned, on Wednesday 8th July 2020, the Independent Medicines and Medical Devices Safety Review published the First Do No Harm Report. This Report, together with the additional supporting documents to accompany it including: Personal TestimoniesOral Hearing TranscriptsHormone Pregnancy Tests Supporting InformationTimeline Key EventsHistory of Regulation and the Press Conference Speech (by Baroness Julia Cumberledge, CBE, Chair of the Independent Medicines and Medical Devices Safety Review) evidence unequivocal systemic failures and a clear link between PRIMODOS and its tragic side-effects.

Marie Lyon, Chair of the Association for Children Damaged by Hormone Pregnancy Tests and active campaigner for justice, since 1978, on reading the First Do No Harm Report, declared “I’ve tried to be very calm and I can’t. It’s the fact it’s been acknowledged. They’ve actually looked at the documentation honestly and openly and for me that is the biggest result for our families today. They will be absolutely overjoyed.”

The Independent Medicines and Medical Devices Safety Review has set out nine recommendations in their First Do No Harm Report. Recommendation 1: states ‘The Government should immediately issue a fulsome apology on behalf of the healthcare system to the families affected by Primodos, sodium valproate and pelvic mesh.’ On the 8th July (the date the report was published) Matt Hancock, Secretary of State for Health and Social Care apologised “on behalf of the NHS and the whole healthcare system” to those who have suffered and their families.

For decades, there have been numerous publications evidencing an association between hormone pregnancy tests and congenital malformations in babies. In 2018 and 2019, Oxford University published an analysis of data which found a clear association relating to Primodos and birth defects. Other supporting research which have found links between hormone pregnancy tests and birth defects includes:

However, there have also been opposing publications which have found no association and/or inconclusive results. In 2017, the Medicines and Healthcare products Regulatory Agency (MHRA) published their report on the use of hormone pregnancy tests and adverse effects related to pregnancy including possible birth defects. The MHRA is an independent Expert Working Group of the UK’s commission on Human Medicines, which was established, in October 2015, in order to conduct this review. The MHRA found there to be insufficient evidence to support an association. Other opposing research includes:

For Marie Lyon, Chair of the Association for Children Damaged by Hormone Pregnancy Tests “after viewing the oral evidence presented by members of the Expert Working Group who were responsible for the scientific publication in 2017, it seems I already have a perfect example of the denial and protection culture endemic in our regulators. Denial when problems occur and protection, not for the patient but for the manufacturer.”

In light of the decades of jostling to and fro of supporting and opposing evidence, it is clearer to understand why the findings of the Independent Medicines and Medical Devices Safety Review in the First Do No Harm Report, together with Matt Hancock’s prompt apology on behalf of the UK Government and acceptance may in the first instance offer some form of relief for the families of the Association for Children Damaged by Hormone Pregnancy Tests.

In the Press Conference Speech by Baroness Julia Cumberledge Chair of the Independent Medicines and Medical Devices Safety Review, she stated ‘In our view Primodos continued to be given as a pregnancy test for years longer than it should. In the face of growing concerns it should have ceased to be available from 1967.’ Yet Primodos remained on the UK market until 1978. This is a failure on behalf of the UK Government to protect its population from harm. Equally, a failure on behalf of the corporation Bayer (Schering). Primodos, was manufactured by Schering in Germany. In 2006 Schering was acquired by Bayer plc.

It is important to point out that Amenorone Forte a hormone pregnancy test prescribed by GPs, during this same time frame, acted in much the same way as Primodos and was manufactured by Roussel in France.  Roussel was acquired by Sanofi in 2004. For this reason families of the Association for Children Damaged by Hormone Pregnancy Tests hold both corporations accountable for the avoidable harm inflicted.

According to the Independent Medicines and Medical Devices Safety Review, History of Regulation, The Medicines Act 1968 received Royal Assent in October 1968, however the ‘transitional period’ meant this Act did not come into effect until 1st September 1971. During this time the Committee on Safety of Drugs was formed, yet it had no legal powers. With little irony, there was no formal regulator, it was part of a voluntary arrangement. There was no body to legally mandate the removal of a drug from the market and limited mechanisms to regulate drugs and restrict their use.

More systemic failures followed because the Committee on Safety of Medicines, (which replaced the Committee on Safety of Drugs, 1st September 1971) focused its gaze on formalising new medicines entering the UK market. Products, including Primodos, which had been on the market before the 1st September 1971 were automatically granted a Product Licences of Right (PLR).

Primodos was awarded a PLR yet its product which had been on the market since 1958, had never been required to submit evidence of quality, safety or efficacy. This oversight to ensure Primodos met the appropriate standards of safety, quality and performance in line with new rules was another missed opportunity to protect public health and safeguard the interests of patients and users.

The Independent Medicines and Medical Devices Safety Review Timeline has brought to light other damning evidence. On 22nd July 1969 Schering UK wrote to Schering Germany recommending the removal of the pregnancy testing indication. In a letter dated 17th February 1970 to Schering, Dr Ruttle a member of the Standing Committee on the Classification of Proprietary Preparations (known as the MacGregor Committee – 1965 and 1971) which provided guidance as to which preparations should be used on the NHS, stated ‘The Committee would be prepared to place the product in A.3 if the promotional indication as a “pregnancy test” were withdrawn and I would suggest that the most appropriate and, acceptable to the Committee, promotion be “symptomatic treatment of amenorrhea to produce withdrawal bleeding.”

On the 9th March 1970 Schering agreed ‘to the deletion of “pregnancy test” from the indications, and to the promotional statement “the symptomatic treatment of amenorrhea not due to pregnancy, by producing withdrawal bleeding”. Further correspondence in April 1970 acknowledged the suggestions from Schering (removing the pregnancy test indication and altering promotional statements) and confirmed that Primodos would be placed in category A.3 (prescription-only medicines).

Five years later, the Committee on Safety of Medicines (an independent advisory committee to the UK medicines licencing authority) published a letter in the British Medical Journal (BMJ) on 26th April 1975. In this letter the Committee on Safety of Medicines stated they agreed with an article published five months earlier in the BMJ entitled Synthetic Sex Hormones and Infants which advised ‘there is little justification for the continued use of withdrawal type pregnancy tests when alternative methods are available.’

On 5th June 1975, the Committee on Safety of Medicines sent an alert letter – to all doctors in the UK – entitled Hormonal Pregnancy Tests, in which they advised them of a possible association between hormonal pregnancy tests and an increased incidence of congenital abnormalities. The Committee on Safety of Medicines stated ‘In view of the possible hazard, doctors should not normally prescribe certain hormonal preparations for pregnancy tests’.

Spanning 1958 to 1978, Primodos was given to around 1.5million women in Britain. Primodos was a hormone pregnancy test prescribed to women to detect pregnancy. It consisted of two tablets which were to be taken on consecutive days. A negative pregnancy test would result in a withdrawal bleed (within three to ten days of consumption of the tablets). It is now known that Primodos prescribed to women to confirm their pregnancy, by today’s standards equates to 13 morning-after pills or 40 oral contraceptive pills. Moreover, the hormones contained in Primodos are now used in the morning-after contraception pill.

A statement taken from the Independent Medicines and Medical Devices Safety Review Personal Testimonies from the families of the Association for Children Damaged by Hormone Pregnancy Tests illustrate their distress – “We feel that we were used as collateral damage by the pharmaceutical company who were developing the contraceptive drug at the time.” The personal testimonies of Nicky Gubbins and Daniel Mason evidence how “The effect on our lives have, as you can imagine, been devastating.” The alleged impacts of PRIMODOS comprise:

  • all congenital malformations
  • more specific malformations:
    • cardiac malformations
    • musculoskeletal
    • neurological
    • neurogenetical malformations
  • birth defects
  • miscarriage
  • stillbirth

The First Do No Harm Report together with the supporting documents is significant because it evidences a clear link between Primodos and the terrible avoidable harms that have been perpetuated for decades through a culture of denial and the absence of state and corporate accountability.

Acknowledgement in the form of an apology on behalf of the Government was the first step towards justice. However, in a letter dated 13th December 2018, to the Independent Medicines and Medical Devices Safety Review, Bayer stated ‘there is nobody at Bayer plc who could usefully contribute anything on the subject matter of your inquiry’. Notwithstanding this response, it is now time to look to the future.

The Government (on behalf of the UK regulators) and corporations Bayer (Schering) and Sanofi (Roussel) should as recommended in the First Do No Harm Report, fund the costs of care for those affected by state and corporate harm. In addition to this, the families of the Association for Children Damaged by Hormone Pregnancy Tests using the Independent Medicines and Medical Devices Safety Review evidence should be able to successfully take legal action for the harms done to them by Bayer, Sanofi and the regulators.

In line with recommendation 9, of the First Do No Harm Report, the Government has a duty to set up a task force which must schedule a timeline for the implementation of the remainder of the recommendations. Such initiatives should endeavor to provide a safety net to ensure that a patient-led approach is centred at the heart of future health care provision.

 

This article was originally published by the Harm & Evidence Research Collaborative on 21 July 2020 at:  https://oucriminology.wordpress.com/2020/07/21/primodos-the-first-step-towards-justice/

 

Contact

Sharon Hartles

Email: sh28739@ou.ac.uk

Twitter: @shartles1

 

Images: Courtesy of author and http://www.ccpixs.com/ via Flickr