Hormone Pregnancy Tests

Gordon Marsden Excerpts

Tuesday 23rd April 2019 Westminster Hall

[Yasmin Qureshi (Bolton South East) (Lab)]

I beg to move,

That this House has considered the Expert Working Group report on hormone pregnancy tests.

It is a pleasure to serve under your chairmanship, Mr Hollobone. I am also pleased that the Under-Secretary of State for Health and Social Care, the hon. Member for Thurrock (Jackie Doyle-Price), is here to respond to this debate.

To establish the context of the debate, I will begin by acknowledging the extraordinary hard work and determination of Marie Lyon, who is here with us in Westminster Hall today. She has led the campaign on behalf of the victims of hormone pregnancy tests, and alongside her husband has travelled the length and breadth of this country, and even been to Germany, to support victims.

It has been my pleasure to work with Marie since the beginning of this campaign, alongside others including Jason Farrell, who has pursued this story for Sky News from the start; Professor Neil Vargesson of Aberdeen University; and Professor Carl Heneghan and Dr Jeffrey Aronson, both of Oxford University, whose recent work is the basis of this debate.

By way of providing more background, I remind the House that Primodos, the hormone pregnancy test drug, was taken by approximately 1.5 million women in the 1960s and 1970s to test for pregnancy. The dosage contained in those Primodos tablets was 40 times the strength of an oral contraceptive that would be prescribed today. There is considerable evidence that many women who took this drug either gave birth to babies with serious deformities, or miscarried, or had stillbirths. Those babies are now in their 40s and 50s, and they have had to live a lifetime with serious disabilities.

To this day, not one Minister or one review has been able to answer some very simple questions. First, why were no official warnings issued about this drug until eight years after the first major report that indicated possible dangers? Why were some doctors still prescribing this drug for pregnant women after official warnings were issued by the Committee on Safety of Medicines? And why were some GPs able to pull out Primodos tablets from their desk drawers and hand them to women?

I secured this debate to seek answers in respect of the Medicines and Healthcare Products Regulatory Agency-led expert working group. That was the scientific review set up on the instruction of a former Minister, the hon. Member for Mid Norfolk (George Freeman), following my Backbench Business Debate on this issue in 2015. He had clearly stated to us that this review would “thoroughly” consider all the evidence.

Such is the depth of concern about this issue that there have already been three debates on the expert working group’s review—this is the fourth. Each and every time, Members from across the House have urged Ministers to consider our concerns about the methodology, the independence of the panel members and the conclusions of the report. On each and every occasion, however, our concerns have been dismissed.

[Gordon Marsden (Blackpool South) (Lab)]

I congratulate my hon. Friend on securing this debate and on the absolutely focused way in which she has conducted this campaign, with other Members here today and with Marie Lyon. I also pay tribute to the hon. Member for Mid Norfolk (George Freeman), the former Minister: it is not easy for Ministers to override the advice of their civil servants, but he did on that occasion. That, however, makes it all the more concerning that, on 24 October last year, Lord O’Shaughnessy wrote my hon. Friend a letter that was rather confusing and defensive, and did not make any reference to enforcing a rethink by the MHRA.

We know that there are issues about how the meta tests are done, and I am sure that my hon. Friend will come on to that. However, at this stage does she still find it very concerning that Ministers have not grasped the nettle?

[Yasmin Qureshi]

I thank my hon. Friend for that intervention and I absolutely agree with him; he can probably hear in my voice some of my frustration about the fact that this issue has not been grasped by Ministers and dealt with.

In recent months, the all-party parliamentary group on hormone pregnancy tests, of which I am the chair, has written to Ministers several times to ask for meetings so that we can discuss these concerns, but each time our request has been declined. Perhaps the Minister here today could shed some light on what exactly the Government are so intent on hiding each time they refuse the request by a group of MPs for a meeting.

Let us not forget that the review was cloaked in secrecy from the very start. As an observer, Marie Lyon was forced to sign a “gagging clause”, which, if breached, could have resulted in a prison sentence. Families who gave evidence to the panel reported being treated appallingly by the MHRA. Despite the MHRA’s insistence that the expert working group was independent, two panel members had to be removed after Marie Lyon discovered conflicts of interest.

Perhaps the most shocking fact was that this review was set up with terms of reference that stated very clearly that it would seek to find a “possible association”, but the review panel and the Commission on Human Medicines chose to ignore that and instead concluded that a

“causal association could not be found between the drug and birth defects.”

Each time that Ministers have been questioned about this review, we have been told that it was

“robust, comprehensive, independent and scientific”.

If that really is the case, I hope that the Minister can provide us with answers today as to why we now have evidence, which I will set out, that clearly proves that the expert working group review was anything but robust and comprehensive.

Last November, a team of experts led by Carl Heneghan, the Professor of Evidence-Based Medicine at Oxford University, conducted a systematic review of all previous human studies. They discovered that when the data is pooled properly it shows “a clear association” with several different forms of malformation. The results were clear that there is an association that is significant. That tells us that the expert working group’s review completely failed to adopt the right approach for a systematic review. Why did it not pool all the data together and properly collate it to show an overall effect? I should also point out that Professor Heneghan’s study has been published in a peer review journal, whereas the expert working group’s review was not even scrutinised.

However, Professor Heneghan did not stop there. Marie Lyon obtained raw data used by the expert working group via a freedom of information request. It is worth noting that despite the MHRA’s claim of “transparency”, this data was not already in the public domain. The cynical among us might ask: why was that? Why hide it?

That raw data was then assessed by Professor Heneghan and his team, who carried out a meta-analysis on it, and again they found that there is an association between the drug and birth defects. Let me just repeat that point again—raw data used by the MHRA for the expert working group review was assessed by independent experts at Oxford University and it was found that Primodos causes deformities.

Can the Minister appreciate why that has led to suspicion that key elements of the research were removed from the report in order for the expert working group to reach its conclusion, and why campaigners feel that Ministers and Parliament may have been misled, given that it appears that key information was being withheld from the report in order to suggest that there is no link between Primodos and deformities?

[Gordon Marsden]

My hon. Friend is being gracious in allowing interventions. Does she not consider it confusing that the group, and indeed the MHRA, seem to be reluctant regarding meta-analysis, when only recently the National Institute for Health and Care Excellence used it to reinstate surgical mesh in the treatment of prolapse? It is widely understood to be a common method—the US Food and Drug Administration and the European Medicines Agency have adopted it. Why are we lagging behind? Perhaps the Minister would like to comment on that in her reply.

[Yasmin Qureshi]

My hon. Friend is absolutely right and I come on to explain how other bodies use meta-analysis to carry out assessment.

Does the Minister understand why we are asking why the data was not even properly assessed? When I tabled a parliamentary question to inquire whether the meta-analysis of the studies had been carried out, I was told that it had not. Can the Minister explain why not? One of the experts on the panel, Professor Stephen Evans, recently made a poor defence of meta-analysis not being used in the review, by relying heavily on a paper called, “Meta-analysis. Schemata analysis”, which was published 25 years ago. The expert working group seems not to have considered meta-analysis an appropriate way in which to assess the data. Why not? Why did it refuse to take an evidence-based approach?

Neither the Minister nor I is a scientist, but she is aware that meta-analysis is the statistical procedure that combines data from multiple studies. When treatment effect is consistent from one study to the next, as with Primodos, it is completely appropriate and evidence-based to use a meta-analysis to assess the data. Pharmaceutical companies use it to approve new drugs. The US Food and Drug Administration uses it. The European Medicines Agency uses it for the approval of drugs, and clinicians and researchers in medicine, education and the criminal justice system use it to determine whether a treatment works. The National Institute for Health and Care Excellence uses meta-analysis, and it is the cornerstone of Cochrane—previously known as the Cochrane Collaboration. The only group that discounts meta-analysis is the MHRA. Why? To say that meta-analysis was not the appropriate method is completely incompatible with an evidence-based approach.

Let me take up the matter of the independence of the expert working group. We have been told several times, by a number of Ministers, that the entire process was completely independent. It is my view that the Government are not well served by their current processes, the lack of independence and the lack of impartiality. What is in doubt is the question of whether the Government have the independent expertise required to hold Government bodies such as the MHRA to account and provide us with independent evidence with which to make informed decisions.

As the Minister is aware, in February 2018, Baroness Cumberlege began a joint non-scientific review into Primodos, sodium valproate and mesh implants, and we expect it to conclude in the next few months. Baroness Cumberlege invited the expert working group to give oral evidence to the review team, and this is how Ailsa Gebbie, the group’s chair, described herself at the beginning of an evidence session:

“I’m also the chair of the MHRA and the expert working group on hormones and women’s health that reviews all products and medicines and drugs related to women”.

What does independent mean if the chair describes herself in that way?

In 2015, the Commission on Human Medicines agreed to establish an expert working group to review the available data on a possible association between the hormone pregnancy test, Primodos, and adverse outcomes in pregnancy, and to make a recommendation. The commission appears to have commissioned the MHRA to do an independent review. Perhaps the independence of the MHRA can be summed up in its response to Marie Lyon, who in conversation with the agency had reminded it of its responsibility to the public interest. She was immediately corrected:

“No, the job of the MHRA is to represent Pharma”.

Of course, the agency is correct—it is substantially funded by the pharmaceutical industry and cannot be considered independent by any stretch of the imagination. Can the Minister explain why we are expected to have confidence in the independence of a review that was run by an organisation part-funded by pharma? How can we be expected to trust claims that Bayer, the manufacturer of Primodos, has no links to the MHRA? Yes, we had a review, but I am not sure we can call it independent. Will the Minister do the right thing and withdraw the expert working group report?

If the Minister needs any further evidence, perhaps I can point her to the testimony of Sandra Malcolm, a recent whistleblower. Mrs Malcolm worked for the manufacturer of Primodos, which is now owned by Bayer. While at the company in 1971, she discovered she was pregnant and spoke to colleagues:

“I was in reception one day and there were two guys there. One may have been a medical rep and he said to me ‘you want a dose of Primodos’ and the other said ‘I think it’s been taken off the market’, and the other one said ‘no, you can get it’. So with that information I went upstairs to see one of the doctors. I said ‘I’m a week overdue and can I have some Primodos?’ And he said ‘I can’t give it to you because it may not work and it may cause deformities’, so I thought that was a definite no.”

Mrs Malcolm said that after the conversation she decided not to take the drug “for obvious reasons” and that she assumed it was no longer on the market. However, many years later, when she saw a report about Primodos causing deformities, she was shocked to discover it had remained on the market for many years after problems had been listed.

Vast swathes of evidence clearly point to a cover-up by the drug company and the Government regulators at the time. It is utterly disgraceful that until this day the evidence has been ignored, as it was by the expert working group review.

--- Later in debate ---

[Emma Reynolds (Wolverhampton North East) (Lab)]

It is a great pleasure to serve under your chairmanship, Mr Hollobone. I begin by paying tribute to my hon. Friend the Member for Bolton South East (Yasmin Qureshi) for having secured this important debate, and more widely for her leadership of the all-party parliamentary group on hormone pregnancy tests and her incredible campaigning on this issue. I pay tribute to all the families who, for many years, have been campaigning tirelessly to uncover the truth about Primodos, particularly Marie Lyon, who is an incredible campaigner. She has worked hard on this issue, and I hope we can do something to make sure we get to the truth about what happened all those years ago. I also place on record my thanks to Professors Neil Vargesson and Carl Heneghan, and to Sky News reporter Jason Farrell for his determination to get to the truth. Many of his reports have been seen by families who have come forward as a result of the testimony and campaigning of others.

One of the families affected by Primodos lives in my constituency. My constituent Steven Bagley was born severely brain-damaged after his mother was given Primodos as a hormone pregnancy test in 1967. Steven needs 24-hour care, cannot communicate, and suffers from a severe form of epilepsy, which means frequent seizures that have become steadily worse with age and happen throughout the night.

I have got to know the Bagley family over the past few years: Steven’s parents Pat and Ted, and his sister Charlotte, who has been a tireless campaigner for justice for her parents and brother. She has recently moved from Southampton back to Wolverhampton to help look after Steven. His parents have lovingly looked after him for 50 years, but are now in their 80s and 70s with their own health problems, and are finding it a real struggle. What I find particularly heartbreaking about the case of my constituents, which is similar to many others, is that like other mums affected, Pat still says, “If only I hadn’t taken those pills.” However, she was doing what we all do: trusting our GP and following their advice. Like many others affected by Primodos, Pat was not given a prescription, but was given the pills directly by her doctor.

It is thanks to the tireless campaigning of families such as my constituents, and of my hon. Friend the Member for Bolton South East, that the Government asked the Commission on Human Medicines to set up an expert working group to examine the scientific evidence linking Primodos to birth defects. However, from the start, serious concerns were raised by the families, the APPG on hormone pregnancy tests, individual MPs and scientists about how that group went about its work. Those concerns have only grown as evidence of missing analysis has come to light, and questions have been asked about the methodology used.

I will raise four particular concerns about the expert working group. First, the group reinterpreted its terms of reference. It was asked to look at a possible association between the drugs and the foetal abnormalities. Despite that, it decided to look for a higher standard of proof of a causal association between Primodos and birth defects, even though it was not asked to find a causal link. It has never been clearly explained why the group chose to interpret and change the terms of reference in that way. Perhaps the Minister will reflect on that when she winds up. If not, will she take that away, consider it and come back to us?

Secondly, the report was altered before publication in several ways. Apparently the draft report, provided to Marie Lyon, stated:

“Limitations of the methodology of the time and the relative scarcity of the evidence means it is not possible to reach a definitive conclusion.”

That line was removed before the final report was published. The draft also stated that

“there is insufficient evidence to determine whether taking the medications at the doses found in Primodos tablets, for two days during the first trimester of pregnancy could have reached and had an effect on the fetus.”

However, in the final report, that was substantially changed. That uncertainty was replaced by the claim that the evidence indicated that any exposure

“was unlikely to have had an effect on the developing fetus.”

In short, the conclusion in the draft report changed from

“the evidence is insufficient to form a conclusion”,

to, in the final report,

“the evidence does not support a causal association”.

Again, there has been no satisfactory explanation for those changes. Will the Minister reflect on that in her winding-up speech or go back to the Department and convey to us why the changes were made?

Thirdly, there was no consideration of possible regulatory failures at the time Primodos was given to mothers by doctors as a hormone pregnancy test. That seems to be a huge omission. Will the Minister explain why such a vital question was excluded? It would surely help us to understand what concerns were raised or should have been raised about Primodos at the time.

[Gordon Marsden]

My hon. Friend is making an excellent speech. She is taking us necessarily into the past. What we know about the past is that how the drugs were marketed in the 1960s and 1970s would be totally unacceptable today. Does she not find it concerning that the context of how the drugs were delivered has not been looked at properly by the report? Some of the potential consequences of that, such as what women took as gospel from doctors, have not been addressed either.

[Emma Reynolds]

I agree with my hon. Friend. It is incredible that the burden of proof seems to rest on the families. That is what is being suggested in debates—not our debates, but others—but the burden of proof actually lies with the pharmaceutical company that made the products in the first place and did not do the testing required. The drugs subsequently had horrific effects on the babies who were born, yet we still have not got a Government or a Minister to accept that there is a link. We are looking for the truth to be uncovered.

I am conscious of time and your advice, Mr Hollobone, but allow me to make a fourth point about the expert working group. The credibility of the group has been further undermined in the eyes of the families and of the Members here today by its not including a meta-analysis—a pooling of all the data from previous studies. It is not clear whether such a meta-analysis was carried out and not divulged, or was just not done. Marie Lyon obtained the raw data used by the expert working group though a freedom of information request. Professor Carl Heneghan of Oxford University used the working group’s own data and found strikingly similar conclusions to his review. Both reviews showed significant associations of the use of Primodos with all congenital malformations and congenital heart defects. Both systematic reviews show that the use of Primodos in pregnancy is associated with increased risk of congenital malformations.

In conclusion, we know that Baroness Cumberlege is carrying out a wider review into independent medicines and medical devices safety. I place on the record my thanks to her and her team for listening to the testimony of Pat and Ted Bagley and their daughter Charlotte. For the first time, they feel like they have been heard and listened to sympathetically. I hope that the Cumberlege review will get to the truth of what happened, but before we do that, it would be useful for the Government and the Minister to get to the truth of why the expert working group has presented the evidence in such a way and to respond to the concerns I have expressed. The sooner we get to the truth of what happened in the ’60s and ’70s with Primodos tablets—they were taken not only by expectant mums in our country, but by others in countries around the world—the better.

--- Later in debate ---

[Sir Mike Penning]

No one in this room or anyone listening to this debate could disagree with that, unless they were a lawyer working for the drug company, the Department of Health and Social Care, or perhaps both.

Believe it or not, Mr Hollobone, 70% of me, you and anyone else in the room is the same as a zebrafish. I swim really well, but I did not realise that until this morning. We chuckle, but the point is that the effects of an experiment on zebrafish will be similar to those on a human being. There are many studies, but the link is important. Professor Neil Vargesson’s report in 2018 supported Professor Heneghan’s report. What does that mean? We all know about the disgrace of thalidomide. Through experimentation on zebrafish, it was proven that thalidomide damaged children. We do not want to experiment on humans. It appears that that is exactly what has gone on here. It is obvious that the mechanism of the action of thalidomide is the same as that shown by the Primodos tests. Everybody can read the technical stuff. There was an effect on zebrafish, who share 70% of their genes with humans. Does that mean it could have had an effect on humans? Of course it does; it is not rocket science.

[Gordon Marsden]

The right hon. Gentleman is taking us through the history. Does he not agree with me that it is extraordinary? We need to remember the chronology. The thalidomide episode took place in the 1960s and was exposed by The Sunday Times and Harold Evans in a great step forward, but the drugs continued to be supplied afterwards. Even now, 40 years later, there is, in the statement of Lord O’Shaughnessy, doubt about whether such things should still be used. We should surely say that they should not be used.

[Sir Mike Penning]

I cannot understand how a drug company, now owned by Bayer, could know what was going on and continue to supply the drug in an underhand way to GPs. As a father—as a human being—I simply do not understand it. What on earth was going on? The MHRA, which gave evidence to us, was in complete denial. We did not ask for a cause. I was lucky enough to be a Minister in seven Departments. If I had said, “This is the review that you are going to do, and these are your terms of reference,” and those terms of reference were changed by the review group without my permission, I would have smelled a rat. I would have thought something was going wrong.

We can go through all the science, which cannot be denied. I do not blame any Minister—I can feel the special advisers’ eyes on my back—but something went dramatically wrong, and it has been covered up by several Governments. That must stop now. If compensation has to be paid, fine. Most of the families simply want an apology. Why is there no apology? Because there would then be the threat of legal action. Mistakes happen. When we make mistakes, we should admit it, no matter what Government are in power. We should sort it. We did that over Hillsborough when I was a Minister in the Home Office. It was a really difficult decision to make, but we made it, and the right conclusion was reached. That should be the case in this instance.

--- Later in debate ---

[Hannah Bardell]

I absolutely agree. I share the hon. Gentleman’s despair and sadness that we are in this position so many years after the group was set up—a process into which the Government put public money and in which medical experts took part. As I have said, we are not necessarily criticising the people in the expert working group, who are medical professionals, but they have fallen victim to a process that was at best opaque and at worst corrupt, given the influence of the companies involved.

Who knows why we ended up in this mess? On the day the report was due to be published, the hon. Member for Bolton South East and I went to an event that we thought was supposed to be public—or at least open to Members of Parliament. We were stopped at the door; some of the press were allowed in, but we were not. We know that there was due to be a press conference and a public event, but they were both cancelled.

Members have spoken passionately about the lack of independence and impartiality, the gagging clause that Marie Lyon had to sign and the heavy-handed approach taken, all of which have caused serious concerns. What does it say to those in the medical community who may be invited to be part of future Government working groups that a group that was supposed to be open and transparent and get to the truth of an issue has turned out to be a cover-up? It raises serious concerns that their credibility will be called into question. That is a very dangerous situation.

As well as looking at the wider issue, we need to look at the mess that the expert group became, so that we can give confidence not only to the families and to our constituents, but to medical professionals.

[Gordon Marsden]

The hon. Lady points out precisely the contextual things that we need to learn. Does she agree that there seems to have been an element of Jekyll and Hyde in the Government’s approach over the past three years? On the positive side, I have confidence that Baroness Cumberlege—with whom I have served on another all-party group—and her team are moving in the right direction. However, everything in the statement that the then Secretary of State made in February 2018 was about the future:

“drive forward…the recommendations of the expert working group…offering the families…a full and up-to-date genetic clinical evaluation…better training and support for obstetricians”.—[Official Report, 21 February 2018; Vol. 636, c. 165-166.]

Those are all good things, but they do not address the past 40 years, offer an apology or express any sense of regret, nor do they address any of the issues raised in this debate. Would it not be a good idea for the Minister to go back to the Secretary of State and say that we need to look again at that 2018 statement, go back to that context and make the necessary decisions? People will not put up with just a broad range of recommendations —we need to get to the heart of the matter.

[Hannah Bardell]

The hon. Gentleman is absolutely correct. How many times must the families and the victims of Primodos have their hopes built up and then completely dashed? Is it not bad enough that they have gone through the trauma, the blame and having their children live with deformities and disabilities—as my hon. Friend the Member for Argyll and Bute (Brendan O’Hara) so precisely and devastatingly highlighted in the case of his constituent—without also having their hopes built up for a review that turns out to be a whitewash? That gives people no confidence at a time when, let’s be honest, confidence in politicians and the political process is not particularly good. We have an opportunity here to do something good, to do it well and to do it properly.

I have to say that my exchanges with the Medicines and Healthcare Products Regulatory Agency and with the expert working group have not been good. I wrote directly to the chair of the expert working group about people’s feelings and concerns, but the response that I received did not fill me with hope.

I am pleased that Baroness Cumberlege has taken on her new role of looking at hormone pregnancy tests, sodium valproate and medical mesh, but when she sought evidence, she did not include Scotland. I have now written to her, and that issue has been rectified, but it is important to remember all the devolved nations of the UK and ensure that they are appropriately included. We know what the academic studies have shown—the work of Carl Heneghan and Neil Vargesson has been exceptional—but there is now new evidence and we should ensure that it is included in any future plans or reviews.

What we need from the Minister is an acknowledgment of the power of the views across this Chamber and across both Houses, and of the serious impact of this issue on people’s lives. How many parents need to die without knowing what happened to their children because of a pill that they took? As the right hon. Member for Hemel Hempstead (Sir Mike Penning) said, these were women who believed that they were in the care of the NHS, that they were being given something that had been properly medically checked, and that they were not being put in danger. However, their health and the health of their unborn children were put in danger. Let us not forget that many women miscarried—there are many children who were not born because their mothers took this pill. This drug was used in Germany as an abortive and in another country as a pregnancy test. It does not take an expert to work out that that was absolutely wrong.

We have a choice, and we have an opportunity. There is a very powerful body of medical evidence that needs to be properly looked at. The Government also need to take a long, hard look in the mirror and think very carefully about why the expert working group failed so badly and why its terms of reference changed part of the way through. They need to make sure that that never happens again; that the victims of Primodos, including my constituent and all the constituents mentioned today, never have to go through any more pain and suffering; and that those victims will get truth, justice and answers to their questions. Do they need compensation? Yes, absolutely, but what they really want is an apology and an acknowledgment.

As the right hon. Member for Hemel Hempstead said, when something goes wrong, the right thing to do is put your hands up and say, “Do you know what? We got this wrong.” It is about time that that happened. I hope that now the Minister and her Government will finally do the right thing.

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[Jackie Doyle-Price]

I come back to my opening comments: we brought forward the Cumberlege review to give an independent challenge to what is currently being done by a regulatory system. We need to look at whether that system is appropriate, given the concerns.

[Gordon Marsden]

The Minister is being very generous with her time. She is seeking to persuade us, perfectly reasonably, that she and the Government have been acting in a measured way to try to look into all these things. As I have said, we welcome Baroness Cumberlege’s report. Has the Minister at any time asked the members of the expert working group why they changed the definition that they were given?

[Jackie Doyle-Price]

I am not satisfied that that is actually what happened. When we receive drafts of reports that are circulated to committees, they often go through amendment.

Let me continue going through the chronology of events. As I said, the evidence did not support a causal association, nor did it disprove one. We will of course continue to review evidence as it arises.