NICE Evidence Review for Use of Puberty Blockers for GD - Now Released

[IDontOnlyLikeJazzFunk]

now released. NC. The full link is below, this is the summary. It's not looking good.

Discussion
A key limitation to identifying the effectiveness and safety of GnRH analogues for children and adolescents with gender dysphoria is the lack of reliable comparative studies. The lack of clear, expected outcomes from treatment with a GnRH analogue (the purpose of which is to suppress secondary sexual characteristics which may cause distress from unwanted pubertal changes) also makes interpreting the evidence difficult.

The studies included in this evidence review are all small, uncontrolled observational studies, which are subject to bias and confounding, and all the results are of very low certainty using modified GRADE. They all reported physical and mental health comorbidities and concomitant treatments very poorly. All the studies are from a limited number of, mainly European, care facilities. They are described as either tertiary referral or expert services but the low number of services providing such care and publishing evidence may bias the results towards the outcomes in these services only and limit extrapolation.

Many of the studies did not report statistical significance or confidence intervals. Changes in outcome scores for clinical effectiveness and bone density were assessed with regards to statistical significance. However, there is relatively little interpretation of whether the changes in outcomes are clinically meaningful.
In the observational, retrospective studies providing evidence on bone density, participants acted as their own controls and change in bone density was determined between starting GnRH analogues and follow up. Observational studies such as these can only show an association with GnRH analogues and bone density; they cannot show that GnRH analogues caused any differences in bone density seen. Because there was no comparator group and participants acted as their own controls, it is not known whether the findings are associated with GnRH analogues or due to changes over time.

Conclusion
The results of the studies that reported impact on the critical outcomes of gender dysphoria and mental health (depression, anger and anxiety), and the important outcomes of body image and psychosocial impact (global and psychosocial functioning), in children and adolescents with gender dysphoria are of very low certainty using modified GRADE. They suggest little change with GnRH analogues from baseline to follow-up.

Studies that found differences in outcomes could represent changes that are either of questionable clinical value, or the studies themselves are not reliable and changes could be due to confounding, bias or chance. It is plausible, however, that a lack of difference in scores from baseline to follow-up is the effect of GnRH analogues in children and adolescents with gender dysphoria, in whom the development of secondary sexual characteristics might be expected to be associated with an increased impact on gender dysphoria, depression, anxiety, anger and distress over time without treatment. The study by de Vries et al. 2011 reported statistically significant reductions in the Child Behaviour Checklist (CBCL) and Youth Self-Report (YSR) scores from baseline to follow up, which include measures of distress. As the aim of GnRH analogues is to reduce distress caused by the development of secondary sexual characteristics, this may be an important finding.

However, as the studies all lack appropriate controls who were not receiving GnRH analogues, any positive changes could be a regression to mean.

The results of the studies that reported bone density outcomes suggest that GnRH analogues may reduce the expected increase in bone density (which is expected during puberty). However, as the studies themselves are not reliable, the results could be due to confounding, bias or chance. While controlled trials may not be possible, comparative studies are needed to understand this association and whether the effects of GnRH analogues on bone density are seen after they are stopped. All the studies that reported safety outcomes provided very low certainty evidence.

No cost-effectiveness evidence was found to determine whether or not GnRH analogues are cost-effective for children and adolescents with gender dysphoria.

The results of the studies that reported outcomes for subgroups of children and adolescents with gender dysphoria, suggest there may be differences between sex assigned at birth males (transfemales) and sex assigned at birth females (transmales).

arms.nice.org.uk/resources/hub/1070905/attachment

It’s so frustrating because detransitioned people, former GIDs staff, parents and women have been raising concerns and calling for more evidence for years now. This makes me really sad and angry for all the kids who have been offered puberty blockers by the NHS or private doctors as a solution to their distress around gender. They and their families have accepted it all in good faith.
It’s scandalous. There absolutely should be a public Inquiry.

How can those trying to get the Bell case appealed still be arguing that under 16s can consent to these unevidenced drugs?
When you’re offered a treatment it should come with clear aims and some certainties about the treatment being able to meet those aims proportionately and safely. That assurance doesn’t seem to be available from taking puberty blockers?
What benefits and clearly outlined risks actually are there for anyone (even an adult) to consent to, for taking these drugs for the purpose of helping with gender dysphoria?
Given all the known health risks and the unknown benefits, why haven’t the UK authorities said that puberty blockers for dysphoria can only be offered to adults as part of a proper clinical trial?

Why is the NHS still offering and funding puberty blockers as treatments for any gender dysphoric patient of any age^ without proper evidence of patient safety and of patient benefit from taking them?

Why has Parliament not spoken up about this?

Why has no one listened for so long to all the different people raising concerns that kids with distress around gender were actually being treated worse than other kids? Because surely that is actually transphobic in an actual literal sense?

These kids have been routinely invasively medically treated with less safety information available than other kids routinely are. They are treated without any long term folllow up, without any proper research structures being put around experimental medicine, and without open public discussion of damning findings as they have emerged. They’ve been treated without being given proper patient information necessary for consent. Even worse, patients have been given essentially false information by some medical professionals- all that crap about just being a reversible harmless ‘pause button’ or breathing space.
And the charities around this have been urging it all on making a mission of child transition for themselves.
A cynic would say that the research isn’t being done at all, or not done robustly, and that attempts at research have been undermined with accusations of transphobia, because some people actively don’t want to know any more detail about all this.
That some people don’t care about the kids well-being. The politics and the optics of the broader movement comes first.
Physically transitioned kids and young people are essential as political posterchildren for a movement. Child transition gathers public attention, public and corporate and government funding, political advocacy and political influence. Yet it seems that children taking puberty blockers ultimately reliably confers only political advantage to some adults. Those adults will never be taking these powerful risky drugs themselves. And the drugs themselves may be harming the children and young people never mind easing their distress at all.

@NecessaryScene1

I did think the refusal to consider parent consent because Tavi said they never used it was the achilles heel of the Bell judgement.

Indeed. But what they said was much stronger than that:

Although the general law would permit parent(s) to consent on behalf of their child, GIDS has never administered, nor can it conceive of any situation where it would be appropriate to administer blockers on a patient without their consent.

Maybe GIDS just have really limited conception ability?

They couldn't conceive they'd lose this JR, and when they did, they said, "oh all right then, let's do it"?

There are cases where a parent can consent to a treatment that the child does not want. The examples here are all tragic, but to give a flavour of it (and not a specific example) a parent can consent to a child having a limb amputated (it gives their child the best chance of survival) even if it is something the child has said they do not want.

In the comment from Tavistock, they are saying that they would not treat a child without the child's agreement. At the time they made that statement the agreement of the child counted as consent. The issue the Bell case ruled on is whether the agreement of the child actually met the legal definition of consent (the child must be competent and adequately informed). It found that it did not, which is subject to an appeal.

Whatever legal standing the agreement of the child has, Tavistock can still require it as a precondition for treatment. If the Bell judgement is upheld the agreement of the child would be termed "assent" and if the Bell judgement is overturned the agreement of the child would be termed "consent".

The point of the case brought by the GLP was, if the agreement of the child does not count as consent, what happens? There is a long-standing answer to this (consent lies with the parents) which the subsequent ruling confirmed. This means that Tavistock are very likely to move to a 3 step approval:

1. Clinicians recommend treatment.
2. Child assents to treatment (since the agreement of the child to be treated as per 1 does not meet the legal definition of consent, at least while Bell holds).
3. Parents consent to treatment (the agreement of the parents to treat as per 1 meets the legal definition of consent by long standing precedent).

A cynic would say that the research isn’t being done at all, or not done robustly, and that attempts at research have been undermined with accusations of transphobia, because some people actively don’t want to know any more detail about all this.
That some people don’t care about the kids well-being. The politics and the optics of the broader movement comes first.

You don't have to be a cynic to say that.

The very first question in good practice would be to examine the ethics and research available. A complete absence of this in a treatment for children is an obvious total failure of these principles.

The first questions should always be : "Does this do harm? Does it do what we want it to do? Are we probably monitoring this to ensure there aren't any adverse issues we should be aware of?"

All normal protocol and safeguarding has disappeared out the window.

There is no research of merit.
There is no following of consent procedures.
There can not be informed decision making in the absence of evidence.

These ethic principles also apply to good practice in politics. Its not the exclusive preserve of medicine. Thats the whole concept and point of impact / risk assessments in public consultations.

Across the board we have seen an erosion in this as the post war political settlement which recognised the need to balance interests to protect the most vulnerable from abuse from more powerful groups and the state has broken down. Its part of a pattern. Safeguarding has been removed because taking care and understanding the need to compromise dilutes power.

Its a warning sign that our entire political system has become corrupted and ethics are no longer important.

This isnt cynical to ask why is protocol not being followed. We shouldn't frame it as a cynical response. We should frame it as the default response that everyone SHOULD be making and asking why the fuck its not.

It’s scandalous. There absolutely should be a public Inquiry

Yes, there should. Not just of NHS either, but an overarching one of the whole raft of lobbying groups, pressure groups and special interest groups, how they have managed to influence and affect policy, strategy, law and guidelines to such an extent.

Who has been using the terrifying - and as far as I can tell - inaccurate narratives about suicidal ideation, and why? Who keeps producing figures out of thin air that are irrelevant to the UK, and using them to pressurise decision makers and influence public opinion?

Who would commission such a review? Who would we ask to start one? Is it more sensible to look at each individual area one by one?

Its a warning sign that our entire political system has become corrupted and ethics are no longer important.

Yes, agree.

This appears to have been just released - the BMJ have now published the Tavistock study that was released just after the Keira Bell case. It's definitely not looking good.

This summary is slightly misleading in that it states that the children finished their treatment at the age of 16 - I can't access the full article but I hope that they explain that only one child didn't progress straight onto cross sex hormones so 'finish their treatment' is a bit questionable as a term.

Puberty blockers used to treat children aged 12 to 15 who have severe and persistent gender dysphoria had no significant effect on their psychological function, thoughts of self-harm, or body image, a study has found.

However, as expected, the children experienced reduced growth in height and bone strength by the time they finished their treatment at age 16.

The findings, from a study of 44 children treated by the Gender Identity Development Service (GIDS) run by the Tavistock and Portman NHS Foundation Trust in London, have emerged as the trust prepares to appeal against a High Court ruling that led NHS England to pause referrals of under 16s for puberty blockers.

www.bmj.com/content/372/bmj.n356.full

In the comment from Tavistock, they are saying that they would not treat a child without the child's agreement. At the time they made that statement the agreement of the child counted as consent. The issue the Bell case ruled on is whether the agreement of the child actually met the legal definition of consent (the child must be competent and adequately informed). It found that it did not, which is subject to an appeal.

The Bell case took them at their word, saying:

It follows that is not necessary for us to consider whether parents could consent to the treatment if the child cannot lawfully do so because this is not the policy or practice of the defendant and such a case could not currently arise on the facts.

That is, the judges directly refused to consider this because they understood the Tavistock to be saying that they would not treat a child if the child could not lawfully consent.

This was noted as a loophole at the time - what if a less-scrupulous provider would do so without legal consent?

But given that the JR was specifically against the Tavistock, the judges did not have to rule, given that the Tavistock said they wouldn't do it.

Now that Tavistock are saying they would do it, that part of the case is now open again. It needs to be brought back up in the appeal, or there needs to be a new JR.

"A cynic would say that the research isn’t being done at all, or not done robustly, and that attempts at research have been undermined with accusations of transphobia, because some people actively don’t want to know any more detail about all this.
That some people don’t care about the kids well-being. The politics and the optics of the broader movement comes first."

It's not cynical, it's a conspiracy theory. Some things are just harder to measure than others, which the NICE report makes that clear if you read it. If you want to answer the yes/no question, do puberty blockers block puberty, that is easy to answer - there are some very obvious signs to look. If the question is, do puberty blockers prevent a worsening of symptoms of gender dysphoria during puberty, how do you measure worsening and how do you separate all other factors that can affect the results?

You do not need people working against research (and the big tragedy here is that happens from BOTH sides in this case) for something that is hard to measure to be hard to measure ... because it is already.

Physically transitioned kids and young people are essential as political posterchildren for a movement.
And one reason for that is that the claimed metaphysics (or whatever the right word is) that underpin all this require it. The late transitioners who claim "I have always been a woman. When I was a kid everyone thought I was a boy but I knew I was a girl" require the existence of contemporary boys who are "really" girls and vice versa.

You do not need people working against research (and the big tragedy here is that happens from BOTH sides in this case) for something that is hard to measure to be hard to measure ... because it is already.

That's undoubtedly true. Lots of effects are very subtle or rare. Particularly side-effects.

But the issue here is that apparently there's supposed to be a massive epidemic problem and this is supposed to be a miracle cure, a life-saving treatment, that will cause countless deaths of "trans kids" if not available.

Given all that hyperbole, it shouldn't be hard to identify at least some positive effect, right?

If we can't clearly see one, perhaps it's time for certain orgs to tone down the hyperbole.

The two strongest effects we seem to be seeing are negative - persistence of gender dysphoria and bone density loss. And it's not clear that there's stronger evidence for any positive effect than we have for the potential negative cognitive effect.

But at least boys end up with less body hair? I guess that works at least, if that's the aim.

If they do move to the 3 step referral as outlined above - clinician recommends, child agrees, parent gives the legal consent - it suggests a consent approach similar to elective rather than clinicly absolutely necessary treatment. This was a point made by a poster on another thread.

I can understand why they absolutely would not do it unless the child wanted it, but it puts it in the realm of cosmetic dental work, rather than treatment to resolve a problem that is causing serious problems for the child's health. In the latter case parents & clinicians would get on with it anyway. But here, the evidence base is so shoddy that it's unevidenced as well as elective.

A father in Canada was put in prison partly because he didn't want his child to have the csh treatment.

A child in Australia was taken away from their parents for similar reasons.

it suggests a consent approach similar to elective rather than clinicly absolutely necessary treatment. This was a point made by a poster on another thread.

Absolutely. If you think you need the child's agreement, then you do not think this is medically necessary.

This is very concerning. I trust NICE, and I've used it (and Cochrane to trawl for medical risks for my family. In summary - there is very little evidence either way, and no substantial well-conducted surveys. There is the big problem of the ethical issues surrounding a double-blind trial, but these are not insurmountable.

I'll await the outcome of the Cass report, but it seems to me that it's now up to people prescribing puberty blockers to conduct a large and well-constructed study to demonstrate their efficacy both physically and psychologically, in particular the benefit or otherwise for those who go on to get hormone treatment.

but it seems to me that it's now up to people prescribing puberty blockers to conduct a large and well-constructed study to demonstrate their efficacy both physically and psychologically, in particular the benefit or otherwise for those who go on to get hormone treatment.

Do you appreciate the fact that it’s a very likely possibility that a large and well-constructed study demonstrates the ineffectiveness of puberty blockers, both physically and psychologically, given the smaller studies that have demonstrated thus?

The problem as noted in the report is easy to see: It would be unethical to give trans identifying kids a placebo, so there is not peer group to review against. So back to gut feel and individual patient response, which from all I have read, the detransition rate is very low.

@NotBadConsidering

but it seems to me that it's now up to people prescribing puberty blockers to conduct a large and well-constructed study to demonstrate their efficacy both physically and psychologically, in particular the benefit or otherwise for those who go on to get hormone treatment.

Do you appreciate the fact that it’s a very likely possibility that a large and well-constructed study demonstrates the ineffectiveness of puberty blockers, both physically and psychologically, given the smaller studies that have demonstrated thus?

Yes, of course, or it wouldn't be a well-constructed survey. Based on this NICE document, the onus is on those who seek to use the treatment to demonstrate its efficacy.

The court in Bell couldn't consider the Q of parental consent because all parties agreed that that was not the Q before the court. It's not a failing of that case.

(And if it had been raised, any ruling on that part would have been that of the GLP case - that yes of course, when a child cannot consent to medical treatment the parents can on their behalf. Because they of course can, and that's fine).

That's why the NICE document is important, and the various meta-reviews all showing the same thing, and the Dutch intervention about "hang on, this is not what we were/are doing at all!"

Because those are moves towards "this is actually not 'medical treatment' at all. This is an experiment, and one where all the data we have so far shows no good results".

I assume (lawyers please advise) that the Tavistock's appeal against the Bell ruling can only be against the Bell ruling, if that makes sense? That they have to argue "the ruling was wrong because yes the child can consent" - they can't say "we've changed our minds and want to act on parental consent instead". At that appeal, I mean.

@MishyJDI

The problem as noted in the report is easy to see: It would be unethical to give trans identifying kids a placebo, so there is not peer group to review against. So back to gut feel and individual patient response, which from all I have read, the detransition rate is very low.

Given the permanent and damaging effect to health of this medication, how many cases of misdiagnosis would you find acceptable?

Each detransitioner who has been through the medical process and possibly the surgery is a product of misdiagnosis.

Do you think it is ethical and wise to apply a 'treatment' to children that has known permanent and damaging effects and no discernible long term benefits?

Is it ethical to base treatment on 'gut feel'?? In my book that is absolutely beyond the pale and I think the medical negligence suits that are inevitable will reflect that.

There is anecdotal evidence of many many detransitioners. Given the extremely poor standard of evidence being used to justify the treatment itself I am not surprised there is no actual research into their failures - no one involved in this seems to be deploying any ethical considerations.

When I say "that's fine", I mean (in case it wasn't obvious) that of course parents can and should so consent where it's necessary! I didn't mean in this particular context.

If giving these drugs to under-18s is to be stopped, it's the problems of the drugs themselves that will stop it, not - or not only - questions of consent. I think that's what the parts of the GLP ruling that talk about whether these drugs are a "special case" was looking towards.

All of these court cases and reviews are just steps sadly - we are a way yet from any firm set of rules being established. (And even when they are there will be the Mad Webberleys of this world to deal with).

www.bbc.co.uk/news/health-56601386

Coverage by the BBC

You can’t placebo puberty blockers because puberty will continue unabated. You can do control group vs puberty blockers group but this possibility has been dismissed as “unethical” because of the “distress” it may cause to not give puberty blockers.

But now we have historical controls: the recent publication of a study that shows if you leave boys alone only a small percentage of them persist.

So now the “unethical” arm of a control group vs puberty blocker group is the puberty blocker group.

There needs to be an immediate moratorium on puberty blockers for moral and ethical reasons, not just legal rulings.

A father in Canada was put in prison partly because he didn't want his child to have the csh treatment.

A child in Australia was taken away from their parents for similar reasons.

Since the High Court ruled children can't consent, we had the lobby groups/organisations/activists saying parents know best and the decision should be down to them.

Apart from when parents refuse, they mean. Because if they really believe parents do know best, they wouldn't be trying to criminalise parents who are rightly cautious.

@Manderleyagain

Physically transitioned kids and young people are essential as political posterchildren for a movement. And one reason for that is that the claimed metaphysics (or whatever the right word is) that underpin all this require it. The late transitioners who claim "I have always been a woman. When I was a kid everyone thought I was a boy but I knew I was a girl" require the existence of contemporary boys who are "really" girls and vice versa.

TRAs used to be quite open about recruiting children to 'demystify' and 'take the sex right out of the trans experience.'

twitter.com/Transgendertrd/status/1013774040509673478

Unfortunately, the video linked in this tweet is no longer available.

You do not need people working against research (and the big tragedy here is that happens from BOTH sides in this case)

This is true of ideology in medicine as a rule.

What makes this NICE document slightly different and I'd argue isn't about both sides at all, is that NICE are saying there just isn't evidence either way. There's nothing. Its a vacuum. The document repeatedly says 'no evidence'.

This is significant and important to note.

We know that there is no follow up being done, once drugs have been used. The onus once drugs have been administered is to prove its doing no harm and is doing what its supposed to. You have to justify your recommended treatment after the fact. The dynamic here is it shouldnt be for not for anti-medicalisation campaigners and researchers to be raising questions about this absence of data. The default is this is the very minimum level of information that should be rigoursly being kept and examine to remove all ability to raise question marks.

Also noting here that the care pathway recommended by the Tavi seems to be is positive affirmation as the default. Rather than more patient / long term watchful waiting approach which is being frowned on by the most vocal lobby groups. Again bias already built in at an institutional level on a complete lack of evidence and follow up.

If you have given out the drugs you have already demonstrated that you believe it works, therefore you have the power in the dynamic and the responsibility to show you are correct. Anti-blocker and hormone groups do not have this power, moral responsibility and do no harm ethical issue at this point. It is the absence of a follow-up up which tilts the issue as being fundamentally one sided and controlled by that side. This is backed up by the fact organised campaigns to block any kind of follow-up research (theoretically likely to be biased in the other way or not) have been pretty much universally successful. NICE's very purpose is to look at all studies in an area of medicine and to assess their quality / bias and whether the study is fundamentally flawed. Those advocating drugs will be aware of this but aren't prepared to trust that medical bodies will actively look out for questionable studies with a nefarious agenda in ideologically sensitive areas of medicine.

If this is about 'both sides' ideological bias then this still doesn't explain the ethical black hole which is the absence of the Tavistock follow up data.

Normally I would argue the toss about both sides on such ideologically sensitive medical issues. On this one i cant because of the balance of power and institutional level failings on basic safeguarding protocol. Its indefensible.

Is it ethical to base treatment on 'gut feel'?? In my book that is absolutely beyond the pale and I think the medical negligence suits that are inevitable will reflect that.

Yes.

In a word.