Primodos EWG Report : Hannah Bardell MP Talks

Will the Primodos victims, and the new science evidence, be at the heart of the Government report ?

On 21 February 2018, Hannah Bardell, SNP MP for Livingston, raised concerns about the Primodos hormone pregnancy test drug, and asked important questions to the Health Secretary.

Primodos EWG Report : Emma Reynolds MP Talks

Will all Primodos victims be listened to ?

On 24 October 2018, Emma Reynolds, Labour MP for Wolverhampton North East, asked Health Secretary to guarantee women who took hormone pregnancy test Primodos will have time to tell their stories to review into claims it caused birth defects and miscarriages.

Families, including one in Reynolds’ constituency, must have confidence in the review. Answers long overdue.

Oral hormone pregnancy tests and the risks of congenital malformations

A systematic review and meta-analysis, October 2018.
Includes Primodos drug victims testimonials.

Overview

  • Sources :
    • read and/or download the full study (free access) Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis, F1000Research, First published 31 Oct 2018, 7:1725, DOI:10.12688/f1000research.16758.1.
    • read and/or download the full study (free access) The Primodos components Norethisterone acetate and Ethinyl estradiol induce developmental abnormalities in zebrafsh embryos, nature, Published 13 Feb 2018, DOI:10.1038/s41598-018-21318-9.
  • Testimonials : read some real stories told by the Primodos victims, see the post comment section.
  • Commenting : scroll down this page until you reach the header “Have your say! Share your views” and the box “Enter your comment here…“.

Abstract

Background
Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations.

Methods

I am fully supportive of this article on the effects of hormone pregnancy tests as it stands. I have no substantive criticism of the content or methods.

Dr David Healy, professor of psychiatry, psychopharmacologist, scientist and author.

We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group. We used random-effects meta-analysis and assessed the quality of each study using the Newcastle–Ottawa Scale for non-randomized studies.

Results
We found 16 case control studies and 10 prospective cohort studies, together including 71 330 women, of whom 4209 were exposed to HPTs.

Exposure to oral HPTs was associated with a 40% increased risk of all congenital malformations: pooled odds ratio (OR) = 1.40 (95% CI 1.18 to 1.66; P<0.0001; I2 = 0%).

Exposure to HPTs was associated with an increased risk of

  • congenital heart malformations: pooled OR = 1.89 (95% CI 1.32 to 2.72; P = 0.0006; I2=0%);
  • nervous system malformations OR = 2.98 (95% CI 1.32 to 6.76; P = 0.0109 I2 = 78%);
  • gastrointestinal malformations, OR = 4.50 (95% CI 0.63 to 32.20; P = 0.13; I2 = 54%);
  • musculoskeletal malformations, OR = 2.24 (95% CI 1.23 to 4.08; P= 0.009; I2 = 0%);
  • the VACTERL syndrome (Vertebral defects, Anal atresia, Cardiovascular anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects), OR = 7.47 (95% CI 2.92 to 19.07; P < 0.0001; I2 = 0%).

Conclusions
This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.

Reactions

Prof. Henegan’s systematic analyses of epidemiological studies, is a scientific review which members of the Association for children damaged by HPT’s have waited over 45 years for. The findings are incredible and mirror the congenital abnormalities suffered by our members. It is a scandal that this epidemiological study was not commissioned by the Government Health Authorities and we cannot thank Prof. Heneghan and his colleagues enough, for the comprehensive and utterly compelling review.

Marie Lyon,
Assocation for Children Damaged by Hormone Pregnancy Tests, UK

Why did Primodos remain on the British market for so long ?

A historical argument for regulatory failure in the case of Primodos and other hormone pregnancy tests

Abstract

The drug Primodos and other hormone pregnancy tests (HPTs) remained on the British market for about a decade after they were first implicated, in 1967, as a possible cause of birth defects.

In November 2017, an expert working group (EWG) set up by the Medicines and Healthcare Products Regulatory Agency (MHRA) concluded against such an association.

However, it was explicitly ‘not within the remit of the EWG to make formal conclusions or recommendations on the historical system or regulatory failures’, a situation that has left many stakeholders dissatisfied.

Placing the question of a teratogenicity to one side, this article takes a more contextual and comparative approach than was possible under the auspices of MHRA. It asks why an unnecessary and possibly even harmful drug was allowed to remain on the British market when a reliable and perfectly safe alternative existed: urine tests for pregnancy.

Based on archival research in several countries, this article builds a historical argument for regulatory failure in the case of HPTs.

It concludes that the independent review which campaigners are calling for would have the potential to not only bring them a form of closure, but would also shed light on pressing issues of more general significance regarding risk, regulation and communication between policy makers, medical experts and patients.

Read the full paper (free access) A historical argument for regulatory failure in the case of Primodos and other hormone pregnancy tests on rbmsociety,

Primodos Hormone Pregnancy Test Testimonials, 2018

Hormone Pregnancy Test Drug Given to 1.5M Linked to Birth Defects

Three mums speak out as they believe it is the primodos drug that left their children with devastating health issues.

The women who were given a hormone pregnancy test have shared emotional stories of the terrible health problems their children are forced to live with.

Reference.

Medicines and Medical Devices Safety Review : Joan Ryan MP Comments

Many critical issues still, despite a step in the right direction

In the Commons, Joan Ryan MP reacted to the UK Government announcing a Review into Primodos, Sodium Valproate, Vaginal Mesh.

During a Ministerial Statement on ‘Medicines and Medical Devices Safety Review‘, Joan Ryan MP raised concerns about the hormone pregnancy test Primodos, following new evidence that has shown that the drug does have the potential to deform embryos.

House of Commons and House of Lords Debates

There have been growing calls for a public inquiry into the “Report of the Commission on Human Medicines’ Expert Working Group on Hormone Pregnancy Tests” scandal, after MPs debated the Primodos drug’s legacy.

Severals MPs have joined the Primodos campaigners to say that the Expert Working Group review was a complete whitewash.

2018

  • House of Lords’ talks ref “Medicines and Medical Devices Safety Review“, 22 February 2018 – 11:48:58 parliamentlive.tv.
  • House of Commons’ talks ref “Medicines and Medical Devices Safety Review“, 21 February 2018 – 12:48:42 parliamentlive.tv.

2017

  • House of Lords’ talks ref “Hormone pregnancy tests“, 16 November 2017 – 17:53:45 parliamentlive.tv.
  • House of Commons’ talks ref “Hormone pregnancy tests“, 16 November 2017 – 10:40:26 parliamentlive.tv.
  • House of Commons’ talks ref “Hormone pregnancy tests“, 14 December 2017 – 15:20:54 parliamentlive.tv.

2016

  • House of Commons’ talks ref “Hormone pregnancy tests“, 13 October 2016 – 15:05:52 parliamentlive.tv.
  • House of Lords’ talks ref “Hormone pregnancy tests“, 21 January 2016 – 11:06:20 parliamentlive.tv.

More About Primodos

 

Medicines and Medical Devices Safety Review : Yasmin Qureshi MP Comments

Is putting three health scandals into one review a good thing ?

In the Commons, Yasmin Qureshi MP reacted to the UK Government announcing a Review into Primodos, Sodium Valproate, Vaginal Mesh.

Setting up another review is not enough, victims deserve better. Asked @Jeremy_Hunt to look at the new scientific evidence together with evidence of regulatory failings that show there was a cover-up. Its time that this was finally exposed and families given answers #Primodos

Yasmin Qureshi Tweets

House of Commons and House of Lords Debates

There have been growing calls for a public inquiry into the “Report of the Commission on Human Medicines’ Expert Working Group on Hormone Pregnancy Tests” scandal, after MPs debated the Primodos drug’s legacy.

Severals MPs have joined the Primodos campaigners to say that the Expert Working Group review was a complete whitewash.

2018

  • House of Lords’ talks ref “Medicines and Medical Devices Safety Review“, 22 February 2018 – 11:48:58 parliamentlive.tv.
  • House of Commons’ talks ref “Medicines and Medical Devices Safety Review“, 21 February 2018 – 12:48:42 parliamentlive.tv.

2017

  • House of Lords’ talks ref “Hormone pregnancy tests“, 16 November 2017 – 17:53:45 parliamentlive.tv.
  • House of Commons’ talks ref “Hormone pregnancy tests“, 16 November 2017 – 10:40:26 parliamentlive.tv.
  • House of Commons’ talks ref “Hormone pregnancy tests“, 14 December 2017 – 15:20:54 parliamentlive.tv.

2016

  • House of Commons’ talks ref “Hormone pregnancy tests“, 13 October 2016 – 15:05:52 parliamentlive.tv.
  • House of Lords’ talks ref “Hormone pregnancy tests“, 21 January 2016 – 11:06:20 parliamentlive.tv.

More About Primodos

 

 

Hormone Pregnancy Test Drug Primodos : Here is Gaynor’s Story

“Made In Birmingham” Interview, 21 Feb 2018

Gaynor Cotterill was born without a left arm after her mother took Primodos. This is her story.

UK Government announces a Review into Primodos, Sodium Valproate, Vaginal Mesh

Baroness Cumberlege will lead an examination of the circumstances in all three health cases and consider whether there are grounds for wider inquiries

The UK Prime Minister has ordered a review of public health scandals involving the hormone-based pregnancy test drug Primodos, the use of vaginal mesh implants and the anti-epilepsy drug sodium valproate.

I look forward to undertaking this tremendously important review and in particular to working with patients to ensure that our health system learns from those it may have failed. It’s essential that voices aren’t just listened to, but properly heard, and that whenever appropriate, the system promptly learns lessons and makes changes.

Baroness Cumberlege, Chair of the review

In the Commons, Jeremy Hunt has announced a review into public health scandals caused by failings in the regulation of vaginal mesh implants, anti-epilepsy drug sodium valproate and hormone-based pregnancy test drug Primodos.

See The Independent Medicines & Medical Devices Safety Review website.

On Twitter

Controversial pregnancy test drug shows deformities in zebrafish embryos within hours of exposure

Primodos drug components can cause embryonic damage in a dose and time responsive manner

“This is a great stepping stone. It doesn’t give definitive answers, but it’s a start, so we can finally put to rest whether or not Primodos caused birth defects

Dr Vargesson says.

The components of a controversial drug, allegedly linked to birth defects in the 1960s and ’70s, caused deformations to fish embryos just hours after they received a dose in new studies by researchers at the University of Aberdeen.

Primodos was a hormone pregnancy test used by thousands of women in the UK between 1958 and 1978.

“The first step was to show the drug has caused problems in fish and hopefully that will lead to some funding for tests on mammals and other tissues to show exactly what is going on.”

Dr Vargesson says.

Research at the time suggested the drug could be linked to a higher risk of women giving birth to babies with abnormalities – a claim denied by Primodos’ manufacturer.

Although Primodos is no longer in use, its components (Norethisterone acetate and Ethinyl estradiol) are used in other medications today including treatments for endometriosis and contraceptives.

“This research helps the campaigners because they can see there has been some up-to-date science being done with modern techniques.”

Dr Vargesson says.

In November last year a UK Government expert working group (EWG) study found no ‘causal association’ between the drug and the abnormalities, stating that outdated methods used by scientists in the 1970s was partly responsible for a failure to find a connection.

Now a new study at the University of Aberdeen, published today in the Scientific Reports journal, has revealed more about the effects of Primodos’ components on the embryos of zebrafish

The paper outlines how after the components of Primodos were added to water around zebrafish embryos, their movement slowed down rapidly; developed changes to the heart within four hours; and within 24 hours displayed damage to tissues such as the fins, eyes and spinal cords.

“I would like to think the PM will take this on board and consider there might be an alternative decision to the one the Commission On Human Medicines made in the Westminster report.”

Dr Vargesson says.

More surprisingly, according to the researchers, the study showed that the drug accumulates in the zebrafish embryo over time. They suggest that if this also occurs in a mammalian species that even a seemingly low dose of the drug for the mother could result in much higher levels for the embryo.

This latest study was led by Dr Neil Vargesson from the University of Aberdeen, who has also published extensive research into thalidomide – a drug used in Germany in the 1950s to treat morning sickness but which caused thousands of babies worldwide to be born with malformed limbs.

“At the moment the scientific research into whether or not Primodos caused these birth defects is inconclusive.”

“What this study highlights is that there is a lot still to be learned about Primodos and more widely its components effects on mammals.”

“Our experiments with the zebrafish embryos shows quite clearly the effects the Primodos components have. This does not mean it would do the same in humans of course, we are a long way from saying that but we need to carry out more research into these components because they are still in drugs today and in some cases in much higher doses than those found in Primodos.”

“The assumption by some previously has been that the doses given to mothers was too low to cause any damage but our study shows that the levels of Primodos’ components accumulate in the embryos over time because they don’t have a fully functional liver that can break down the drug. This too is new information and if the same thing happens in mammals, these drugs could build up in the embryo to much higher levels than shown in the mother’s blood.”

Dr Vargesson explains.

More About Primodos