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

The atmosphere that has been whipped up around PBs with Mermaids and others describing them as 'life saving' has been disgraceful particularly when we are talking about an experimental treatment with long term consequences. Proper clinical decision making requires a cool head, an objective approach and rigorous evidence all of which have been nigh on impossible to get with fevered activists waving suicide statistics around and clinicians finding themselves pilloried for trying to get to the truth. NICE reports carry weight so lets hope this will finally provide the objective evidence that cannot be denied.

Usually trials are funded by the pharma company, charities or government. Trials are vvv expensive, these trials would need to be life long so ££££££.

If they are being prescribed with crappy evidence, then why would companies invest in the research. I wouldn't trust any trial funded by a TRA charity they would be hugely biased, so that leaves government. If they do allow prescribing to continue then they will absolutely need to pony up for the trials.

Does this happen with other drugs where there is a poor outcome of evidence to support their efficacy?

Yes. Beta-interferon was a big one for MS. Pharmaceutical companies poured huge amounts into promoting it, including funding and 'support/information' for patient groups who then also pushed for its use. I am not sure where the evidencw for beta interferon is now but when first considered by NICE the evidence did not support its use. Some sort of fudge was agreed in the end becauae of public pressure.

Drug companies pour huge amounts into getting things through NICE approval because the american insurance companies take their reviews seriously.

In my field a new drug would not be allowed to be prescribed outside a clinical trial until it had approval from Nice. I don't know how puberty blockers were approved for proscribing.

Drugs are approved/licensed by MHRA - not all go through NICE. Puberty blockers are not licenced for this use; they are prescribed off-licence.

NICE reports carry weight so lets hope this will finally provide the objective evidence that cannot be denied.

This was why NICE was formed - to be a weighty central body in a position to say an evidence-based "yes" or "no" to experimental new treatments being touted as miracle cures (or just life extensions) for cancer or whatever by drug companies to desperate potential patients.

This does seem like it could be potentially their toughest challenge yet though. So many organisations are invested in this snake oil.

That's the problem; they're used off license so much that the general public think it's an official "treatment."

Pbs are being featured in mainstream tv series.

They're mainstream.

Pressure groups obviously have a huge hand in this.

@Belleende

I am so glad this has been through Nice. I work in another field of medicine and I know just how high the standards are for efficacy and value for money to get any treatment approved.

It has been staggering to me that anyone has been allowed to prescribe children experimental drugs, with known, severe and permanent side effects outside of a well defined randomised clinical trial.

If this went through the usual approval routes as a clinical trial, I am not sure how it would get past an ethics committee.

It is yet another example of how usual practices, that are there to safeguard people, have been trampled over in the name of transgender rights. It is so so damaging.

It’s good NICE finally got round to looking at it. One of the reasons I assumed the use of these drugs and protocols were well established and relatively safe was because I trusted the NHS to have done due diligence. That they had not has been a real eye-opener.

Though this confirms what I had thought having looked through deal of the evidence presented by transactivists, it’s truly worrying to consider how much harm is potentially being done to children all over the world.

One of the key issues which seems yet to be grasped is the reliance on WPATH to inform UK health and social care as the provider of 'international best practice'. There is a definite need for investigation into this lobby group and examination of the evidence basis of the claims it makes and papers it has endorsed.

@MaudTheInvincible - that Huxley quotation is bloody chilling.

I have wondered for some time why NICE has had nothing to say about puberty blockers. So glad they have addressed it at last.

I have always had faith that it would be the NHS and the various associated organisations such as NICE and the CQC as well as a few well targeted court cases that would bring the show down.

The USA with its fragmented, private/insurance based commercial health system is ripe for introducing a highly questionable but profitable range of treatments, especially when combined with the power of an extremely noisy and demanding customer base.

I wonder if things would have moved so far in the wrong direction if these had been new drugs rather than existing drugs being used for a new purpose.

The lack of research is more unusual for a pharmaceutical intervention. Drug companies prefer the 'overwhelm them' approach to NICE reviews. They also use a range of sneaky measures: selectively reporting positive outcomes from a large range of study outcomes, testing against a placebo or sub-optimal alternative rather than the best available alternative, very selective inclusion criteria for participants in a trial, short term follow up... They go to quite some effort to get drugs approved.

Yes R0, WPATH are not an official professional association; they are a lobby group of self interested people. I believe Susie Green is a member?

I remember a statement on the mermaids we I saying that they follow the WPATH standards of care...

Why are these studies so poorly conducted?

Poor design.
Difficult to understand ethical decisions that let some of those older studies proceed.
This week I've seen an objection to a brain study (relating to sex) on the grounds that any results might be disturbing to the participants because it's in a contentious area- and this might be sufficient to reconsider the ethics approval.

To be fair, it's (sadly) not that unusual for a systematic review to include of lot of low GRADE evidence categorisations - but they'd normally contain some RCTs rather than observational trials.

Normally commissioners would want the nod from Nice before paying for them.
Agreed. I don't know if there have been individual case applications made but I don't know how much the drugs as such cost.

NICE has "highly specialised health technology appraisals" but they are for ultra-rare conditions which is why they can have some leeway about the types of evidence taken into account.

Ahh, of course off licence, they probably started life with another purpose and have morphed into this.

Not all new treatments go through Nice approval. The benefits of some advances in radiotherapy for example were so self evident that practice changed without the need for a Nice appraisal.

Getting cancer drugs approved for off label use in cancer is a total ball ache. If it is not approved or in the cancer drug fund it requires huge amounts of paperwork between the drug company and the Clinician to access it. Many Clinicians won't get involved because it takes so much effort. I bet the process is so much easier for puberty blockers.

I have wondered for some time why NICE has had nothing to say about puberty blockers. So glad they have addressed it at last.

NICE doesn't spontaneously decide to scrutinise an area - it has to be invited to do so by the NHS (for England and for Wales) or by DHSC.

It’s good NICE finally got round to looking at it.

Even now they wouldn't be looking at it if it were not for Keira, Transgender Trend, The Times, BBC Newsnight and many more brave lone voices. GIDS were certainly not calling for it

Yes R0, WPATH are not an official professional association; they are a lobby group of self interested people. I believe Susie Green is a member?

I'm more concerned that the NHS Service Specification for children and adolescents is so reliant on WPATH guidelines, especially as the GIDS then has responsibility for being the 'expert' service influencing Primary Care, schools, colleges, social work and voluntary sector.

Gender Identity Development Service (GIDS) for
Children and Adolescents
(extract)
The service will be delivered in line with:
 emerging evidence for best practice
 relevant national and international guidelines for the care of children and adolescents with GD such as the World Professional Association for Transgender Health Standards Of Care For the Health of Transsexual, Transgender and Gender Nonconforming people, (Version 7 2012) (referred to in this document as WPATH SOC v7) and the Endocrine Society’s Clinical Guidelines (2009);
 NICE guidelines specific to the treatment of mental and emotional health and wellbeing including for psychosis, anxiety and depression."
www.england.nhs.uk/wp-content/uploads/2017/04/gender-development-service-children-adolescents.pdf

I wonder do any of the royal colleges have anything to say on PBs?

Ahh, of course off licence, they probably started life with another purpose and have morphed into this.

Off-topic: but there have been some cases recently where pharma companies bought the rights/distribution for an off-label drug that has been used for a very long time. The company x8 - x10 the price so it had to go to NICE with its marketing authorisation for a specific indication (for which it had previously been off-label) so that it could become approved. Unfortunately - the price has been found prohibitive for the evidence base that does exist (which tends to be unimpressive) so the application has been rejected. The people who were already on the drug for that specific indication get to remain on it but it's no longer available for those who are newly diagnosed with that specific disease.

Will be very interested to see what coverage it gets.

Will the Guardian touch it? Will Jesse bloody Singal?

‘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.

EmbarassingAdmissions do you mean off-label or off-patent? There has been a recent issue with hedge funds buying up production of off-patent drugs which used to cost the nhs pennies each and putting the price up significantly. And because some of these drugs are so widely used this adds hugely to the nhs drugs bill.

Puberty blockers are used for prostrate cancer.