Uterine Roulette and Consent

This post continues with the Lonesome Heroines theme – Consent. It needs reading in conjunction with Peter Selley’s Coming Clean on Neonatal Deaths.

The fact these posts deal with vaccines is semi-irrelevant – they are about a development model, a playbook, set up with SSRIs that industry now apply across all products.

Our Bodies, Ourselves, a book by the Boston Women’s Health Collective was first published in 1970. Women taking court cases about the treatment they were being given for their breast cancer were a major stimulus. These women helped create the idea of informed consent – see Lonesome Heroines.

Even an Irish male teenager could tell OBOS was groundbreaking. Ireland had/has a strong matriarchal streak and although the Catholic Church back then denied sex happened in Ireland, Irish women were getting hold of OBOS. Fintan O’Toole’s We Don’t Know Ourselves covers some of the wonderful encounters that played out

OBOS was taking on the establishment. It’s not doing that now. It is a velvet glove in which the iron fist of the establishment dictates what women get to know about their bodies. What OBOS might now be up to played out in RxISK posts a decade ago – The Dark is for Mushrooms, Preventing Precaution and Mumsnet. (There were mixed views in the RxISK Team as the posts make clear).

Silent Health last week touched on tricky related issues. We seem to be in transitional times with what was once the Left seemingly now the handmaidens of Big Pharma and maybe Big Business more generally and what was once the Right becoming the People’s Party. Exemplified by the War between the Naomis.

The word ‘seem’ is important here – it is difficult to know what is going on. Yanis Varoufakis has us reverting to Feudalism – an argument made by Alain Supiot a decade ago in Governance by Numbers.

In Women Pregnancy and Clinical Trials we hinted at the idea that Women’s Bodies are once again a place where a new reality is playing out.

A Decade Ago

Long before clinical trials of vaccines in pregnancy began to be pushed as a way of empowering women, Lisa Christian and colleagues from Ohio State University did something interesting.

All women are advised to get the flu shot when pregnant. Flu vaccines are also given for another reason to healthy volunteers – to provoke an inflammatory reaction. Could they be producing an inflammatory reaction in pregnancy? There are routine blood tests for inflammatory markers like the C-Reactive Protein test (CRP), so this is easy to test.

The answer is yes vaccines can cause inflammation – women who get the flu shot when pregnant show elevated levels of CRP.  The Christian paper says it’s a mild response – so what’s the concern?

Knowing nothing about events that unfurled a decade later, Christian and colleagues say that an inflammatory response predisposes to developing pre-eclampsia and to preterm births.

Medical histories tell us preeclampsia has been recognized for millennia, long before most other medical problems. It was called toxaemia because it could kill a pregnant woman and her baby.

It’s main feature is that the woman’s blood pressure rises malignantly toward the end of pregnancy – in the third trimester. Gestational hypertension can also happen in pregnancy but is benign. The incidence of pre-eclampsia is rising but we don’t have good figures on this. Even if not fatal, it can shorten a woman’s life and leave her with enduring health problems.

The cause of pre-eclampsia is unknown, but views now lean toward implicating the placenta and placental inflammation.

Inflammatory responses, with or without pre-eclampsia, also predispose to pre-term births, which can affect the child for the rest of its life. Quite aside from its effects through pre-term birth, eclampsia can independently affect a child’s neurodevelopment – leading to autism, ADHD, cerebral palsy and other conditions.

Maternal RSV Vaccine Trials

A decade later, Eric Simoes. Beate Kampmann and colleagues were involved in the commercial development of a maternal RSV vaccine given to pregnant women. Routine blood samples were done but either CRP was not done or if it was, it wasn’t reported.

This feeds into a larger issue that applies to Covid, RSV and other commercial vaccine exercises in pregnancy. There were no Phase 1 (safety) studies done to test for safety factors like this before going ahead to recruit thousands of women to commercial trials. Regulators do not appear to have asked for Phase 1 trials because the idea of doing trials in pregnant women is so new, and there is such a rush to ‘empower’ women that protocols have not been put in place to ensure that the risks some women take leave us in position to inform all women in a proper fashion.

What we do know is that in these later RSV commercial trials, women who got the vaccine were more likely to develop pre-eclampsia and their babies were more likely to have a pre-term birth

We also know that a GSK commercial exercise for an essentially identical vaccine was terminated early because of a marked increase in the incidence of pre-term births and a doubling of neonatal deaths.  We don’t know about pre-eclampsia or inflammatory marker rates because GSK have not released the data.

Pfizer also started a Covid vaccine commercial exercise but terminated it early after 348 of a projected 4000 women had been recruited. We don’t know why. The data are not available over a year after the market development exercise terminated and whatever data will be made available will not be released before June 2024. The protocol for this exercise says nothing about inflammatory markers.

The health of both mother and baby in these commercial exercises is of vital importance. Finding out what might cause pre-eclampsia, a mystery for nearly 3000 years, is also of importance. We are told on all side that only randomized controlled trials will give us evidence that we can rely on – but it seems that the only thing companies are looking for in these exercises is evidence that might support a commercial benefit for them.

All companies need do to get a license from regulators to claim they have an effective vaccine is to show a 0.5% reduction in rates of hospitalization for RSV. Even if an infant needs to go into hospital, RSV almost never leads to death. This absolute risk reduction is misleadingly transmuted into an 84% effectiveness gold (in relative risk terms) and enormous pressure is put on women to get the vaccine and governments to fund it.

The vaccine marketing does not mention any risks to the mother or the baby – risks that these studies seem to have gone out of their way to avoid finding.

The Licensing of RSV vaccines

FDA convened the 181st Meeting of the Vaccines and Related Biological Products Advisory Committee prior to approving the Pfizer Maternal Vaccine. It was chaired by an unusually independent woman – Hana El Sahly – a Professor of Molecular Virology at Baylor College of Medicine’s Vaccine and Treatment Evaluation Unit in Houston.

Women in most Western countries now get Flu and TDAP (Tetanus, Diphtheria and Pertussis – Whooping Cough) vaccines. They are now also being offered Covid and RSV vaccines and soon will be offered GBS – (Group B Streptococcus). All can cause inflammatory reactions.

Hana’s questions about these agents gave rise to a remarkable scene at the meeting.

Hana

On the question of co-administration with Flu and TDAP, we worked hard with our colleagues in the OB/GYN community to bring up the vaccination rate to where they are against these two pathogens.  One of them [Pertussis] causes mortality in the infant, one of them [Flu] causes significant morbidity in the mother.

There seems to be a narrow window to vaccinate, if the data presented by the FDA holds true.  With a vaccine that diminishes TDAP responses by 20% as an estimate, but perhaps as low as less than a half, given the confidence interval, and that lowers responses to Flu antigens by 15% or 20%, from an implementation standpoint, what are we going to tell our OB/GYN colleagues to prioritize?

Are we confident that giving these vaccines together or closer than one month apart, that we would not be negatively impacting the health of the mother and the child?

This is probably a question more for the FDA.

WTF

A lot of nervous committee members avoided going near this question. The hot potato was eventually dropped in the lap of Joe Toerner of FDA. There is a gorgeous clip from this meeting From Hana to Joe – from which this transcript comes – the section of the video between Hana and Joe really cannot be transcribed. It is hard to find the right word to describe it, perhaps – hilarious.

Joe

It’s a great question.  I look forward to your discussion about this topic.

We presented the data that was under review.  All the data that is part of our review end up in product labelling, so in product labelling we place all the information that we think is relevant.

It would be up to the provider to understand what’s in labelling, to understand the data on the co-administration and come to a determination about vaccine administration.  Our position is labelling is our deliverable to you all – labelling.  We convey important information on labelling so that a provider can make a determination of use of the product.

Hana

I will open the floor to my colleagues to weigh in on this, but I can begin by indicating that these data are concerning – the issue of preterm labor aside, which is also very important.

Given the window, given the interference with these antigens, and given how critical we think these two immunization programs are for pregnant women, making sure that, should this vaccine be licensed until we know better, it cannot be co-administered.

Chaos?

FDA, likely as instructed by Pfizer, accepted a label that recommends not giving the RSV vaccine until 32 weeks. This will mean there almost cannot be a preterm birth – but it doesn’t get rid of all risks – see below.

In contrast, EMA have licensed the vaccine for use from 24 weeks onwards.  When ‘we’ asked why the difference from FDA’s 32 weeks, on December 1 EMA stated:

Regarding the difference between the EU and US indications for the vaccine, please note that EMA and FDA are two distinct regulatory authorities. Although there is cooperation between EMA and FDA, companies send separate applications to the EMA and FDA. The evaluations are carried out independently by each agency, following the existing legislation in either the EU or the US. This may result in different outcomes or differences in the conditions for use.

Pfizer have split the difference in the British label where the vaccine is recommended between 28-36 weeks.

A Twist in the Tale

There is a further twist to this tale. Most American and European authorities and guidelines covering pregnancy cite paracetamol – acetaminophen as the analgesic of choice in pregnancy.

So if a woman develops an inflammatory response after any of the 6 and soon 7 vaccines she gets, this is what she is likely to reach for.

It risks causing premature closure of the ductus arteriosus which is a channel in our hearts that remains open while we are in the womb but closes at birth when blood begins to flow through our lungs. If it closes prematurely it can lead to pulmonary hypertension.

Over 20 years ago, Merck viewed premature ductus closure and pulmonary hypertension as a serious enough problem to warn women not to take Vioxx during the third trimester of pregnancy. What does Vioxx have to do with acetaminophen – paracetamol? Well both are Cox-2 inhibitors.

FDA have been wondering for the better part of 20 years whether they should require warnings about taking this drug in pregnancy, especially the third trimester. EMA haven’t been around for 20 years, but they too are looking at this and so far have not opted to do anything, which FDA likely use as part of their justification for doing nothing

No Laughing Matter

Joe Toerner’s contribution above is no laughing matter. Rarely, if ever, has anyone put FDA’s role more succinctly – something that almost no-one ‘gets’.

I was fortunate to be part of a group that petitioned FDA not to rush to complete the approval of the already EUA’d Covid vaccines. When FDA ignored us, some of my colleagues wrote to them pointing out a bunch of anomalies in FDA’s position.

FDA responded with a sneering letter that seemed to me among other things they had likely had fun composing. Among the many points was this:

It is important to note that FDA’s authorization and licensure standards for vaccines do not require demonstration of the prevention of infection or transmission.

A vaccine can meet the licensure standard if the vaccine’s benefits of protecting against disease outweigh the vaccine’s risks for the licensed use.

If we accept 84% (relative) rather than 0.5% (absolute) efficacy, the benefit side of the maternal RSV Vaccines maps onto FDA approval – although the risk element may not.

But the key point is my colleagues were, likely still are, wedded to the idea that FDA are in the business of protecting the public health. They aren’t. Joe makes this clear. Doctors (he calls them providers) have to make the key decisions about your health and mine. On their way to ticking some boxes, FDA curate company material from which a label gets written, primarily by the company. End of story.

It’s not entirely the fault that some amazing colleagues, in my opinion, got this one wrong.

In this Hilarious Video, keeping a very straight face, Emer Cooke of EMA claims it is EMA’s role to keep Europeans Healthy Safe and Well. She goes on to say EMA employs thousands of scientists, implying just to do this – keep us safe.

EMA waste vast amounts of money employing people with a science background as bureaucrats, along with having Emer as CEO and designing her twitter feed so you get regular updates on her reading list. Having a human face to the bureaucracy is more important to EMA than safety.

It’s only when someone like Emer gets put on the spot the way Joe was you find them backing away as they have in correspondence with me – when they end up saying, as Joe did, its a doctors job to keep people safe.

EMA and Joe become inarticulate when asked what exactly is it doctors might do to keep people safe? Doctors aren’t by chance supposed to exercise a judgement call and tell a woman that in their opinion vaccines in pregnancy will increase your risk of pre-eclampsia and pre-term birth – when EMA and FDA resolutely say there is no statistically significant data that this is the case?

Virgin Territory

Part of EMA and FDA’s brief is, in agreement with industry, to set the boxes that the regulator then ticks.  Boxes, for instance, to cover what needs to be considered when running commercial trials of vaccines in pregnancy.

At present are no boxes. In May 2022 FDA and EMA agreed to think about setting up harmonization committees to work on this new area. This is why there were no Phase 1 trials of the RSV or Covid Vaccines. No checking beforehand whether this vaccine could cause an inflammatory response that might trigger pre-eclampsia or pre-term birth.

The trials that went ahead got approved by Ethics Committees (IRBs) who were unaware that they were approving the recruitment of women not just to take vaccines that have not been tested for safety but to experiments that have been drawn up on the back of an envelope and not tested for safety.

The pregnancy focus up till this has been on first trimester issues – does this drug cause birth defects? Is it teratogenic? Once companies show its not, the assumption is that its safe to take. But these commercial studies on RSV vaccines open a window on the third trimester and all that can go wrong there.

The GSK and Pfizer studies combined point to an inflammatory hypothesis of pre-eclampsia – See Coming Clean on Neonatal Deaths.

If commercial exercises are going to be run in pregnant women – in order to empower them you realise – we need to put a lot more boxes in place. These would cover routine maternal blood tests rather than drawing blood on neonates for antibody levels. They would aim at giving us good data on implantation issues, miscarriage rates, pre-eclampsia and pre-term births. They would insist on analyses of placentas after the birth and many other things.

The resulting data would be made publicly available pretty well immediately. If Albert Bourla is eagerly anticipating using A.I. to have the results of these adverts published in the New England J of Misinformation within days of the business venture terminating, women should demand that the data collected gives them the information they need and that they have access to it even before Pfizer get to run their adverts.

There was a time when women refused to be brushed off by doctors telling them not to bother their pretty little heads about the best treatment for their breast cancer – that was the doctors job. Doctors have been replaced by Regulators and Companies deciding what women should be told. Except for a few awkward dames like Hana El-Sahly, many women, including bioethicists, now seem to figure that getting used to being in the dark is empowering.

Time was when the BMJ took on issues like this – the working model for its new incarnation the BMJJ is incapable of doing so.

Time was when Women’s Health Collectives rattled the cages women were kept in.

The Times They Have Changed.