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

Off-label but used for the indication.

Usually very, very cheap drugs that change ownership and suddenly have a substantial price increase.

And I recognise the scenario you outline - and yes, very expensive. It's one of the causes of conflict for hypothyroidism in the UK iirc because that happened a few years ago with T3. Didn't that increase x9 or something?

I don't which which patient group it was but one of them spotted the potential group for this to happen for them and they negotiated with the original company to buy the rights themselves. Very smart move that kept it an affordable treatment.

OP, it looks like the review was completed in October 2020. Was it only posted online recently? Why would they not have made it available earlier given the active court cases?

I don't which which patient group it was but one of them spotted the potential group for this to happen for them and they negotiated with the original company to buy the rights themselves. Very smart move that kept it an affordable treatment.

Not wanting to derail, that's interesting. There's the official BTF British thyroid foundation, which operates under the BTA (association) and wouldn't be able to do that.

There are a couple more groups/ charities eg thyroid U.K. and stop the thyroid madness.

There's been a lot of smearing of the btf on social media by the others.

@MrsToddsShortcut

‘The content of this evidence review was up to date on 21st October 2020’

I hope that when the Good Law Project appeal against the Bell vs Tavistock ruling takes place in June, that this is used to absolutely flatten their case.

I don't think anyone is allowed to submit new evidence, are they?

Not wanting to derail, that's interesting. There's the official BTF British thyroid foundation, which operates under the BTA (association) and wouldn't be able to do that.

I gave hypothyroidism as an example of a group of patients that had been badly affected by a price hike. They're not the patient group I meant which was a rare condition with an orphan drug iirc (and it was the rights to this drug that they purchased).

There is no such thing as a transexual child. A child presenting with body dysmorphia needs the same help as an anorexic-talking therapy to accept their body & live healthily.

I bet the process is so much easier for puberty blockers.

I wonder why?!

Where does this leave gender Gp et al?

No change I presume but how on Earth can political parties be seen to support them?

So ... apologies for my ignorance - is this this:

'NICE will also undertake a thorough review of the latest clinical evidence to help inform the working group’s review.'

from this:

www.england.nhs.uk/2020/01/update-on-gender-identity-development-service-for-children-and-young-people/

When is the working group to make its report or publish findings, etc?

Guessing this might have some significance to the Cass review as well.

I get the impression that the cass review won't report for some time. They set up a twitter account to give updates back in January but it hasn't tweeted since 1st feb, and there is no sign of the promised Web site yet. That suggests to me it's at the very beginning of the work.

Will the NHS continue to appeal the court's ruling that children cannot consent themselves to use this drug, having seen this?

twitter.com/thecassreview

'more from us soon' - that was in feb

@ArabellaScott

So ... apologies for my ignorance - is this this:

'NICE will also undertake a thorough review of the latest clinical evidence to help inform the working group’s review.'

from this:

www.england.nhs.uk/2020/01/update-on-gender-identity-development-service-for-children-and-young-people/

When is the working group to make its report or publish findings, etc?

Terms of reference:

It is expected that findings and any recommendations on this aspect of the review will be reported early in 2021 with the review’s wider findings and recommendations delivered later in 2021.

@PosyP

OP, it looks like the review was completed in October 2020. Was it only posted online recently? Why would they not have made it available earlier given the active court cases?

I assume it has been going through a review process since then - it has only just been released - I've been keeping my eyes open .

Maybe they've just been staring at it in horror, wondering what to do with it...

@WarriorN

Where does this leave gender Gp et al?

Private clinics don't have to prescribe only effective meds -they can prescribe what they like as long as they don't mis-sell (a whole other argument). @lecanardnoir on Twitter is experienced at taking "alternative" medicine to task.

Thanks, Embarrassing. 'later' - bit vague!

@ArabellaScott

Thanks, Embarrassing. 'later' - bit vague!

It's typically a bit less vague but, for a number of topics, a lot of clinicians have been redeployed for Covid or Covid-related cover reasons so the timetables have been a little blurrier than is the norm for the last year or so.

Guessing this might have some significance to the Cass review as well.

The report draws itself to the Cass review's attention - so did the "parental consent" court ruling from last week.

I am neither a lawyer nor a medic or any kind of scientist and if any of what I say next is entirely wrong in those contexts I would outright welcome correction - these issues are so important and I want to learn, not least so that next time I write to my MP (or to a Select Committee or whatever) I don't make a fool of myself.

But I think what we are looking at with all this is a refining and repositioning of stuff, legally and medically - and that Good Law Project's touting of itself as achieving anything is mendacious entirely.

Keira Bell Judicial Review: confirms existing law that children cannot consent to what they cannot understand. "Introduces" (or rather, highlights) the concept that puberty blockers are an experiment not a treatment, based on the medical evidence presented (and more importantly not presented) to the court. This was an important judgment because the NHS had been acting as if children could consent; they can't.

Good Law Project JR: confirms existing law that where a child cannot consent to medical treatment, parents can. That really was all, and it was a waste of their time and money; that had never been in question anyway. This was not an important judgment (unless GIDS use it to change their processes, which would be outrageous and which they have not. Yet at least).

Situation so far: children whose parents do not want them to be will not be drugged by the NHS though of course the situation for the likes of GenderGP is basically not regulated; and parents like Susie Green will still be able to get their way via that route. As will children off their own bat, where the likes of GenderGP are prepared to overlook all ethics. (And there is of course as there should be a grey area for NHS patients already on the drugs).

NICE review: There is no good evidence of anything; what there is is not reliable or of any quality; what there is shows harms (to some extent, bone density, cardiovascular issues) and perhaps some goods (possibly psychological well-being, but there is certainly no good evidence). This - it seems to me - reinforces the "this an experiment, this is not a treatment" theme from Bell.

So after those three things surely what we have is a situation where a) only parents/carers can decide ultimately that their child should take these drugs b) any ethical doctor can only ask those parents "do you consent to this experiment" not "do you consent to this medical treatment".

You would of course also hope that a load of doctors are sitting up and going "Whoah, wait a minute" and no doubt many are - but at this point I doubt that the doctors that "matter" - the ones in the actual field, because they are often going to be the most "captured" - are thinking that. But, every little helps.

As I say I would really welcome correction from people that actually know what I'm talking about - as robust as you like.

But - I think - that is sort of the framework that the courts and NICE are telling the Cass Review to operate in.

Out of interest (and I read it entirely as a layperson, and fairly fast at that) the NICE document does not seem to have even considered effects on IQ. Is that right? I appreciate that studies on that are even more sparse than the studies they did study, but that seems to me to be something of an omission?

I'd say that's a good round up themost

Not sure about the IQ bit.

@TheMostBeautifulDogInTheWorld

Out of interest (and I read it entirely as a layperson, and fairly fast at that) the NICE document does not seem to have even considered effects on IQ. Is that right? I appreciate that studies on that are even more sparse than the studies they did study, but that seems to me to be something of an omission?

There's so little evidence of the effects on IQ/white matter/frontal lobe function it's really hard to call.

Its also the long (life time) unknowable/unforeseeable side effects - increases in cancers for instance? Or increases in diabetes anaemias? will this affect the thyroid glands brain liver? Dementia? Who knows? & that's the worry!

@TheMostBeautifulDogInTheWorld

Out of interest (and I read it entirely as a layperson, and fairly fast at that) the NICE document does not seem to have even considered effects on IQ. Is that right? I appreciate that studies on that are even more sparse than the studies they did study, but that seems to me to be something of an omission?

They did mention it but as with most of it the research wasn't adequate to enable them to draw any conclusions:

Cognitive development or functioning
The study by Staphorsius et al. 2015 in 40 adolescents with gender dysphoria (20 of whom were receiving GnRH analogues) measured cognitive development or functioning (using an IQ test, and reaction time and accuracy measured using the Tower of London task):
• The mean (±SD) IQ in transfemales receiving GnRH analogues was 94.0 (±10.3) and 109.4 (±21.2) in the control group. In transmales receiving GnRH analogues the mean (±SD) IQ was 95.8 (±15.6) and 98.5 (±15.9) in the control group.
• The mean (±SD) reaction time in transfemales receiving GnRH analogues was 10.9
(±4.1) and 9.9 (±3.1) in the control group. In transmales receiving GnRH analogue it
was 9.9 (±3.1) and 10.0 (±2.0) in the control group.
• The mean (±SD) accuracy score in transfemales receiving GnRH analogues was73.9 (±9.1) and 83.4 (±9.5) in the control group. In transmales receiving GnRH analogues it was 85.7 (±10.5) and 88.8 (±9.7) in the control group.
No statistical analyses or interpretation of the results was reported.