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NHS England has finally released the PATHWAYS puberty blocker trial protocol. The reason it’s almost a year late could reasonably be supposed to be because of the impossibility of the task. How to devise a trial structure that will give any meaningful results or information we don’t already know? And how to get past the ethical review board a medical trial on children that causes irreversible harms with no clinical rationale and no evidence of benefit?

Despite failing in the first task NHS England has succeeded in the second. We have previously written about why a puberty blocker trial can never be ethical here. The PATHWAYS trial protocol is simply evidence that it can’t be done.

This trial will not provide us with the definitive evidence promised. The study to end all studies, the one to prove once and for all whether blockers are harmful or helpful (an impossible goal in itself) will inevitably fail to do so. The results will be just as muddled and contested as every other study. It won’t put an end to the ‘polarised views’ and the ‘toxic debate’, it will only add more fuel to the fire.

Trial design

The design of the trial is so bad it will inevitably increase the polarisation of views.

The trial structure couldn’t be more biased towards getting the desired ‘positive’ result. More qualified people than us have explained the problems in trying to extract meaningful data specifically about blockers from out of all the confounding factors, such as the fact that these children will also be receiving therapeutic support.

In fact the Cass Review warned against this very thing in its analysis of the Dutch study (de Vries et al., 2011) that started off the use of puberty blockers internationally:

2.12 A confounding factor was that all patients in the Dutch service were seen regularly by their psychiatrist or psychologist whilst on puberty blockers, so it is difficult to separate the therapeutic effects of these sessions from the role of puberty blockers alone. [P 68]

Why make the same mistake again?

The Cass Review lists other factors that would bias a study towards getting the results the researchers want:

There are many other potential problems, some of which include: – unconscious bias in questionnaire design where the questions are written in a way that prompts a more favourable response; – using the wrong kind of analysis for the available data; – not following up for long enough to see the full benefits or harms of a treatment; – seeing an improvement because patients were improving spontaneously over time [p 51]

The questionnaire ‘what best describes your gender identity?’ gives an NHS-sanctioned authority to everything children have been taught by activists, schools and the media, including a list of gender identities Stonewall would be proud of. The only thing this will tell us is how much a child has already imbibed the ideology, and the questionnaire itself will further reinforce their learned beliefs. If NHS England thinks it’s possible to be ‘mainly a boy or girl’ or ‘neither a boy or girl’ and that you are either ‘cisgender’ or ‘transgender’ then it must be true.

Another questionnaire reinforces the concept to parents. The About Yourself questionnaire asks ‘Do you identify’ as: ‘woman/man’ or ‘non-binary/genderqueer/agender/gender fluid’ as if these things are equivalents. Any parent who has had doubts about their child adopting a ‘gender identity’ is put straight by NHS England – all of this is real.

The follow-up term of three years is nowhere near long enough. Short-term follow-up is a known way to get ‘good’ results from studies in this area, the literature is full of them. They’re the kind of studies the Cass Review either rejected or judged ‘low quality.’ There is a recognised ‘honeymoon period’ after getting blockers, this is exacerbated by the placebo effect and the fact that children have learned that blockers are necessary, life-saving care. They have been taught to expect nothing less than ‘trans joy.’

For the children on the PATHWAYS trial, there is the added incentive to report positive results because of the pressure to keep this option open for other ‘trans kids.’

A lot is riding on this particular trial and children will feel the responsibility. Children who are given blockers immediately will report that they are happier than those who have to wait another year, not only because that’s an obvious result of getting/not getting what you want immediately, but also because of the immense external pressures to give the ‘right’ answers.

This is not a randomised control trial (RCT); the delayed group is not a control group. The comparison is between children who desperately want blockers (probably supported by their parents) and children who don’t; two completely different groups.

The observational group HORIZON INTENSIVE, which is described as a ‘non-randomised control group’ will not be matched based on the critical factor of clinical eligibility for puberty blockers. Those on the puberty blockers trial can opt in to the CONNECT sub-group so not all will get brain monitoring. How many children will choose to get brain scans on top of the barrage of questionnaires they’ll be subjected to?

Ethical concerns about experimenting on children are explained away by informing us that ‘suppressing puberty as a component of intervention for gender incongruence can only be performed during puberty, limiting it to adolescents.’ [p 25]. Are we to understand that normal ethical rules don’t apply to a treatment that blocks a child’s puberty for the reason that it needs to be done during a child’s puberty?

The fact that it did get through ethical review is a scandal on a par with the last puberty blockers study, and it is inexcusable given what we know now – ironically, knowledge gained through the Cass Review which recommended it.

But it’s worse than that. The foundational basis of the trial takes us straight back to the gender-affirming care model that the Cass Review so comprehensively dismantled and rejected.

After four years of an NHS-commissioned independent review which re-established reality and normal standards of NHS care, we’re back to square one. We’ve ended up with a trial that takes us from the evidence of Cass back to the ideological belief of the Tavistock, a service that was judged to be unsafe and closed down.

In the politicisation of childhood the activists have won.

Conflicts with the Cass Review

In fact the Cass Review provides cover; they can say ‘we’re following Cass’. Technically, yes. Cass did recommend a puberty blockers trial to ‘fill in gaps in the evidence.’ But this trial won’t do that and it is antithetical to the overall aims and conclusions of the Cass Review. Without the results of the data linkage study it is simply negligent. The fact that the Tavistock was so disgracefully inept at data collection for the previous puberty blocker trial is no justification to run another.

Going ahead with more experimentation on children before we know the longer-term outcomes of around 9,000 children who went through the Tavistock GIDS, including an estimated 2,000 on blockers, is indefensible. It is a prioritisation of one recommendation in the Cass Review over 31 others that should have been established first before it was even considered.

The data linkage study was also commissioned to ‘fill some of the gaps’ in follow-up data in order to ‘develop a stronger evidence base.’ This would have given us crucial data without any risk to a new cohort of children. It was scuppered by the adult clinics refusing to co-operate, yet despite that the puberty blockers trial is given the green light. For the activists apparently it pays to obstruct research.

We do have reliable evidence from all published studies, including the Tavistock’s Early Intervention Study, that the vast majority of children who take blockers progress to cross-sex hormones, as the Cass Review found. The protocol admits:

‘This rate of gender transitioning was substantially higher than those reported from earlier observational studies, prior to the use of GnRHa.’ [p 21]

So a trial on blockers alone will not give us the full picture of damage caused to children’s bodies by starting on this medical pathway. The real question is what happens when we block children’s natural sex hormones and later inject them with hormones of the opposite sex? The trial is based on the fiction that blockers are a standalone treatment but the evidence shows that once on the pathway children don’t get off.

The trial is not ‘accepting the Cass Review in full and implementing it’ as Secretary of State Wes Streeting has claimed. It is allowing the manipulation of the priorities and the direction of the new gender services for children, using the Cass Review as justification.

Look at the evidence: NHS England has failed to review cross-sex hormones, failed to adequately update the clinical commissioning policy, failed to develop a clinical formulation and test any therapeutic models, failed to complete the data linkage study, failed to set up the bridging service for 17 – 25 year-olds and failed to set up the new service for detransitioners.

But they have succeeded in getting a puberty blocker trial approved.

In other words, following the Cass Review NHS England has failed to implement key recommendations that serve to safeguard children and gone ahead with the one recommendation that puts children at risk.

Worse, the puberty blocker trial undermines the function and purpose of the recommendations NHS England has begun to put in place. The more rigorous assessment and psychotherapeutic model that is the real change in approach recommended by Cass cannot serve its purpose while puberty blockers are put on the table as an option, or dangled as a prize for the most persistent children.

All therapeutic work is distorted by holding out the promise of blockers. The work to develop a clinical formulation and psychotherapeutic models is incomplete; how will this not revert to ‘assessment of readiness/eligibility for blockers’, even with the best of intentions? This is the route the Tavistock inevitably took.  

The Cass Review Recommendation 7 provided clear eligibility criteria:

Long-standing gender incongruence should be an essential pre-requisite for medical treatment but is only one aspect of deciding whether a medical pathway is the right option for an individual. [p 35]

Yet the trial requires that children have experienced ‘gender incongruence’ for only two years. This captures the ‘rapid onset’ group of children for whom these feelings begin at or after the onset of puberty.

Cass notes ‘the change in prevalence from birth-registered males to birth-registered females’ and that:

The current profile of transgender presentations is unlike that in any prior historical period [p 118]

This is the very group who are most likely to have been caught up in the social contagion driven by activists, the media and in schools, and it is the group we know least about. Cass said:

but if potentially dynamic psychosocial or sociocultural factors predominate in a significant proportion of people, one of the most challenging ethical questions is whether and/or when medical intervention is the correct response. [P 193]

Surely we should find out the answer to this ethical question first? It is an added vulnerability in the cohort eligible for the puberty blocker trial: we are working blind with a group of children when we don’t yet know what the problem is. They are already drawn from the most vulnerable groups of children. From the Cass Review:

31. This is a different cohort from that looked at by earlier studies. Among referrals there is a greater complexity of presentation with high levels of neurodiversity and/or co-occurring mental health issues and a higher prevalence than in the general population of adverse childhood experiences and looked after children. The increase in referrals and change in case mix is also being seen internationally. [P 26]

The other group who were over-represented in referrals to the Tavistock are children with emerging same-sex attraction. There are serious questions about why the most vulnerable children are suddenly self-identifying as ‘trans’ and until we have answers to some of those questions they should not be offered the most invasive and life-changing option for treatment.

We have written about our concerns about autistic children specifically. Exploratory objective no 3 of the trial is:

Do risk benefit profiles vary according to presence or not of neurodevelopmental disorders or high levels of neurodevelopmental trait levels?

Birth-registered sex and neurodevelopmental disorders are the two factors that feature in all the PATHWAYS research measures. As it is teenage girls and autistic adolescents who are driving the unprecedented rise in referrals of a completely new group we know little about, it makes sense to study the factors of being female and being autistic. But not this way. This trial puts at risk the very group that least fits the historic profile and most fits the profile of those likely to be influenced by ‘psychosocial or sociocultural factors.’

The exclusion criteria for the puberty blockers trial requires only that mental health issues are ‘stable.’ This echoes the criteria in the old WPATH-based clinical commissioning policy for cross-sex hormones which has not been updated to align with the Cass Review and the new service specification. It is another example of NHS England looking like they are following Cass while in the background it’s business as usual.

It is the job of the Secretary of State to see the whole picture, not to use the excuse of ‘following the experts.’ Who else is to hold NHS England to account? Wes Streeting has said:

“It is a scandal that medicine was given to vulnerable young children without proof that it was safe or effective, and outside the rigorous safeguards of a clinical trial.”

There is still no evidence (and never could be) that blocking a child’s puberty is ‘safe or effective’ and the trial has no rigorous safeguards.  We are still looking at a scandal.

Wes Streeting is well aware of the gender activism within the NHS, there really is no excuse to be so naïve as to trust that the Cass Review recommendations will be implemented properly, consistent with the overall and most critical aim: the establishment of a new model, in line with normal standards of paediatric care.  

The trial’s foundation in ideology

The study synopsis tells us: “The medical condition or disease under investigation is Gender Incongruence.” ‘Gender incongruence’ is neither a medical diagnosis nor a disease.   

The definition of gender incongruence is taken from the International Classification of Diseases (ICD-11) which includes a ‘Strong desire to be a different gender than the birth-assigned sex’ and a ‘Strong desire to ‘transition’ and live as the experienced gender.’  Or as Stonewall would put it:

“Trans is a word that describes people who feel the gender they were given as a baby doesn’t match the gender they feel themselves to be” (An Introduction to Supporting LGBT Young People, 2015, p.5)

For proponents of ‘gender affirmation’ like Stonewall, Mermaids and Helen Webberley, blockers are the first step on the ‘gender-affirming care’ medical pathway, the goal of which is to ‘match’ the body to the inner feelings.

This is the basis of the PATHWAYS experiment on children.

Cass doesn’t use the term ‘assigned sex’, except in definitions of the ICD-11 diagnosis or in relation to DSDs, where it is applicable. The Cass Review final report predominantly uses ‘gender dysphoria’ and introduces a new term ‘gender-related distress.’ On page 16 Cass tells us:

“this Review is strictly focused on the clinical services provided to children and young people who seek help from the NHS to resolve their gender-related distress.”

The Cass final report explains the difference between the classifications from ICD-11 compared with the Diagnostic and Statistical Manual of Mental Disorders (DSM-5):

Explanatory Box 5: Gender incongruence: A marked and persistent incongruence between an individual’s experienced gender and the assigned sex (ICD-11). Gender dysphoria: Clinically significant distress or impairment of function (DSM-5). [P 83]

Although the DSM-5 definition of ‘gender dysphoria’ also includes stereotypes of behaviour in childhood, it is classified within mental health and requires that a child is suffering a level of distress of ‘clinical significance.’

But the designers of the study have chosen to use the wholly ideological ICD-11 classification influenced by WPATH.  It was an activist goal to move the classification out of the “Mental and behavioural disorders” chapter and into the “Conditions related to sexual health” chapter in order to officialise their claim that being trans is not a mental health issue.

So we have a trial on children, some of whom may be as young as nine, based not on their mental health but on their ‘sexual health.’ We need to wake up.

Using the ICD-11 classification is a choice. It has nothing to do with medicine, it is a purely ideological diagnosis both conceptually and in its language.

The part of the ICD-11 classification of Gender Incongruence of Childhood which is left out of the trial synopsis is the bit that makes it clear that this is about a child not fitting stereotypes: ‘make-believe or fantasy play, toys, games, or activities and playmates that are typical of the experienced gender rather than the assigned sex.’

Gender Incongruence of Adolescence and Adulthood tells us:

Gender Incongruence of Adolescence and Adulthood is characterised by a marked and persistent incongruence between an individual’s experienced gender and the assigned sex, which often leads to a desire to ‘transition’, in order to live and be accepted as a person of the experienced gender, through hormonal treatment, surgery or other health care services to make the individual’s body align, as much as desired and to the extent possible, with the experienced gender.

In other words ‘embodiment goals.’ The FAQ on the trial emphasises this with the statement that a longer-term ‘helpful’ effect of the treatment would be ‘better alignment of body shape with gender.’ In other words, prioritisation of cosmetic appearance over biological function, ideologically framed as ‘living as the experienced gender.’

A patient’s desire for a specific medical treatment is not a part of any other diagnosis, nor a clinical rationale for giving the treatment in any other area of NHS healthcare.

Built-in activist bias

The question is why, out of two problematic classifications, did the trial team choose the purely activist one? Reading through the protocol, there are other indications of bias towards an activist position throughout, from the theoretical framework to the language used and the claims made.

The second point of the inclusion criteria, after the clinical diagnosis, is this:

Request for puberty suppression persists after receiving other care prior to the initiation of GnRHa.

The inclusion criteria reinforces this part of the ICD-11 ‘diagnosis’ as if demanding treatment is indication that the child needs it and should have it. Children are incentivised to get through the therapeutic treatment and just keep on insisting on blockers. The more fixed on this ‘solution’ and the more demanding the child, the more chance they have of ‘succeeding.’ The fixation on blockers is not seen as a cause for concern, but as a rationale for giving the child what they want.

The protocol makes the unevidenced claim on page 21: ‘Gender incongruence is often a lifelong condition,’ a claim that is repeated on page 26:

‘Gender incongruence can be a long-standing, even life-long, experience.’

In fact, all the evidence for children shows the opposite: historically the vast majority naturally grew out of these feelings by the end of puberty or early adulthood if they weren’t ‘affirmed’ and socially transitioned. The Cass Review is clear on this. To suggest that modern, learned ‘gender identity’ in children is fixed for life is pure activist rhetoric to justify blocking the critical period of growth that in the vast majority of cases would be the cure.

The following passage is also revealing:

Proponents have argued (without basis) that suicide rates have increased since the UK implemented a ban on the use of GnRHa for this indication. At the other extreme, it has been alleged that GnRHa has long-term physical adverse effects and disrupts what should be psychological exploration of gender and gender distress. [p 21]

This compares 1) ‘argued’ sensationalist claims that have been proved false with 2) ‘alleged’ justifiable concerns about long-term effects and a proven claim that blockers don’t work as a ‘pause button’ that gives a child ‘time to think.’ This reasonable position is presented as the opposite ‘extreme’ to totally unsubstantiated scare-mongering, despite the fact that these very issues were raised in the Cass Review.

The next claim fails to mention that for up to a third of study participants in the previous Tavistock puberty blockers study, their mental health worsened:

In particular, in relation to mental health, psychosocial functioning and quality of life there was inconsistency among studies showing either some improvement or no change with initiation of GnRHa. [p 25]

Why try to hide the negative outcomes?

The following justification for blocking a healthy child’s puberty suggests that children with a ‘strong desire to be a different gender than the birth-assigned sex’ are comparable with childhood cancer patients.

While due care and attention should be applied when considering research in children and young people, we also note that the failure to undertake research has disadvantaged their health. For example, cancer outcomes in young people lagged behind those in adults until there was a concerted effort to develop and test new interventions for childhood cancers. [p 26]

The use of childhood cancer, a devastating, diagnosed medical condition, where the choice in a medical trial would  literally be between an experimental treatment that may cause harm versus probable early death, is an offensive comparison that reinforces the activist claim that blockers are ‘life-saving care.’

We are told that the trial is ethically sound because of ‘clinical equipoise’:

In summary, an RCT of GnRHa in children and young people with gender incongruence is ethically sound because of clinical equipoise and the need to conduct the study in this age group.

Clinical equipoise is the term used to describe a genuine uncertainty among experts as to whether a proposed treatment is helpful or harmful because the evidence is inconclusive, and it is the justification for conducting a trial to determine which side is right. In the case of blockers, the disagreement is between proponents of evidence-based medicine on the one side and ideologues and activists on the other.

The evidence that blockers prevent pubertal development is uncontested, as is the evidence that the vast majority will progress to cross-sex hormones. The risk of future infertility and loss of normal adult sexual function for children on this pathway from early puberty is normal medical knowledge; the risk of harms to bone and brain development likewise can be medically predicted. The only uncertainty is whether blockers improve or worsen mental health.

The inconclusive evidence on short-term mental health benefits is being used to justify a trial on a drug that has evidenced serious and harmful effects on long-term physical development. There is no comparison.

The primary outcome for the trial is ‘quality of life,’ using a vague, subjective measure of general wellbeing.

Mental health problems can be treated in non-invasive ways that carry no risk to a child’s healthy physical development. Mental health is not the priority here, it is a diversion. The focus on mental health outcomes distracts from the serious medical interventions on the physical body that the trial proposes.

And it is unethical to trial a treatment because there is uncertainty as to whether it causes brain damage in children.

The problem for NHS England is that activists have historically been allowed to influence and dictate children’s treatment pathways in this area, and blind-faith believers in ‘gender affirmation’ are embedded in the service.

‘Expert responses’ were published in an article in Science Media Centre. Dr Cass said:

“My review uncovered a very weak evidence base for benefits from the use of puberty blockers for children and young people with gender dysphoria. In fact some children had more negative than positive effects.

However, given that there are clinicians, children and families who believe passionately in the beneficial effects, a trial was the only way forward to make sense of this.”

A knowledge of weak evidence versus a ‘passionate belief.’ This is not clinical equipoise.

The significant factor that is not addressed anywhere in the PATHWAYS research is the extent of cultural indoctrination these children have experienced online, in schools and throughout the media. No other generation has been brought up in today’s new reality where feelings are more real than objective facts; this is unprecedented.

Of course the children ‘passionately believe’ blockers are beneficial; this is what they’ve been taught. Their parents either become true believers themselves, or go along with it out of fear of losing their child.

The FAQ concedes that the recent group presenting to the clinic are different to previous groups but uses this as an excuse not to look at follow-up data for the previous study, concluding ‘So, it’s important to study the needs and experiences of this specific, current group of young people over time.’ It is as if these children are being viewed in a cultural bubble, impervious to the influence of activist groups that target them, the youth culture that promotes the message and the peer pressure to join in.

The PATHWAYS ENGAGEMENT advisory group of young adults with ‘gender incongruence’ likewise will be fully subscribed to the view that ‘gender-affirming care’ is essential. We can predict what their view will be in their role to advise on ‘all aspects of the programme, including outcome measures, patient involvement in research and strategies for long-term patient engagement, interpretation, and communication of findings.’

A final point about the language used in the protocol. Activist groups are renowned for using the term ‘young people’ to cover up the fact that we are talking about children, a word they avoid. ‘Children and young people’ seems to have now become the accepted terminology in this one area of NHS healthcare – it doesn’t fit with Child and Adolescent Mental Health Services (CAMHS) for example, and it is misleading.

The Cass Review uses Children and Young People but there is some variation in the text of the report and a few examples of ‘child’ or ‘adolescent’ used alone.  

The trial protocol uses ‘children and young people’ and abbreviates it to the dehumanising ‘CYP’, making it even easier to forget that these are children, not units of measurement. Perhaps this can be explained by space constraints in the protocol document but that doesn’t excuse the following two examples which illustrate the misleading picture we get when ‘young people’ is used instead of ‘children’:

There will be no upper limit imposed by research consent on how long young people have to consider and then explore fertility preservation options [p 39]

Young people aged 12 and above will complete the ALSPAC Romantic Relations measure, which assesses whether young people have engaged in any of the 14 sexual behaviours from the Adolescent Sexual Activities Index [p 54]

Any person under the age of eighteen is legally a child. In this area of healthcare in particular, that should not be forgotten or obfuscated by misleading language. It is children who are being asked to consider their future fertility and it is children who are being asked, before the age of consent, what sexual behaviours they have engaged in.

This is why definitions are so important. What safeguarding measures are in place to address the incidence of a girl who is sexually active before the age of consent? This should automatically be included in the exclusion criteria for the trial, and a matter for investigation.

In the case of girls, wanting to be a boy and engaging in underage sex are both indicators of potential sexual abuse; taken together they should be a red flag warning. Does imprecise language cover this up? And what are the safeguarding procedures in place for this?

New research

The Cass Review was a stepping stone in the direction back to evidence-based care; it gave us the medical evidence and raised questions about the social factors influencing the recent cohort. But it was limited: Cass is not an ethicist or a social scientist and we need wider research in order to understand what is going on with the unprecedented rise in ‘trans’ identities in this generation. Cass acknowledged the limits in current knowledge and the need to continue to look at and learn from new research:

In conducting this Review I have had to make recommendations based on the currently available information. I am very aware that this is a point in time and as new evidence is gathered different insights might emerge. I have recommended a service model that has inbuilt mechanisms to be able to evolve and adapt with the emerging research overseen by appropriate governance structures both within individual NHS organisations and at a national level. [p 15]

There is new research from the US which draws on the Cass research and extends it. It is also a wider exploration of the social phenomenon and adds critical analysis to our knowledge in this area. We have written about the HHS report and how it compares to the Cass Review here.

It is the responsibility of NHS England to consider new research which, as Cass says, will ‘build on the work undertaken by the University of York and maintain an up-to-date understanding of this complex and fast-moving research area, a living systematic review’.

Conclusion

The puberty blocker trial is based on the reality-denying beliefs of trans activism, not the evidence-based findings of the Cass Review.

The strength of the Cass Review was its neutrality. Without that, people would have had a good excuse not to read the evidence which was so comprehensively researched and so critical to people’s understanding. It would likely not have been accepted in full by both main political parties. The Cass Review moved us a huge step forward at a time when we had virtually nothing. But it is also its weakness.  

Without a framework of critique of the transgender project and its targeting of children, even those with the best of intentions can lose sight of the most salient fact: that we are stopping children from going through puberty. That is not right, and it is not ‘anti-trans’ to say so. We are causing irreversible harms to a child’s healthy development with no clinical rationale, and creating lifelong medical patients. This is not something NHS England should be doing full stop.