Tavistock puberty blocker study published

[PaleBlueMoonlight]

www.bbc.co.uk/news/uk-55282113

Finds 43/44 (98%) progress from PBS to cross sex hormones

The pre-print version of the paper (www.medrxiv.org/content/10.1101/2020.12.01.20241653v1.full.pdf) described why 3 children/young people came off the puberty blockers before going back on them. In relation to one study participant they said a "birth-registered male, stopped GnRHa for 9 months to attempt to store sperm, contrary to their earlier decision not to, and restarted afterwards"
The use of the word "attempt" suggests that sperm was not attainable. There is no mention of the fact that a child changed their mind about future parenthood within a really short time in the discussion and it is not recorded as an "adverse event" as it should be. Loss of fertility is surely an adverse event! (it reminds me of that paper in JAMA on mastectomy in girls and young women- there's no mention of breastfeeding at any point!)
If I'd been the reviewer of this paper I would want to know more about this. Why did they child change their mind? What can be learnt from the fact that this occurred? What happened for that child in their time off the puberty blockers, psychologically and physically? Were they able to obtain sperm and what is the significance of being able to obtain it or not? Were there any other children of young people who expressed regret or concerns about loss of fertility even though they did not come off the puberty blockers?

Yes. I'm not sure that really stands up as a reason not to have a control arm. Data for a short period remains useful even if some discontinue because they want to seek treatment elsewhere.

Despite this selected cohort being assessed as having persistent and severe gender dysphoria the treatment section seems to suggest some questioning of the chosen course of action during PB treatment:

Three participants had brief periods off GnRHa prior to their 16th birthday. In one, treatment was withdrawn by clinicians due to non-attendance at clinics and restarted 4 months later. Another requested a period off GnRHa to think further about treatment in view of other things happening in their life; they restarted 4 months later. A third, birth-registered male, stopped GnRHa for 9 months to attempt to store sperm, contrary to their earlier decision not to, and restarted afterwards.

...One young person decided to stop GnRHa and not start cross-sex hormones, due to continued uncertainty and some concerns about side-effects of cross-sex hormones. The remaining 43 (98%) elected to start cross-sex hormones.

*It looks as though at the start of the trial, 46.7% of the children were showing moderate to severe autism traits, and after 1 year on puberty blockers, that figure rose to 58.6%.

I hope I've got that wrong. Can someone familiar with the SRS test for autism make sense of this table?*

I can't comment on the table but one child I taught who was referred to the Tavi was only later referred for autism; this was over 10 years ago though. It's possible some children were diagnosed during the time there.

It's very concerning that it looks like for some their difficulties increased.

That may have not been a direct result of the pbs though; some young people with diagnosed and undiagnosed autism find puberty v hard due to the intense social nature of it.

I spotted sentence referring to autism/ SRS. To be reported at a later date....

The Social Responsiveness Scale (SRS) was a baseline only assessment of autistic traits; these data will be analysed in the future.

This is shocking, but regardless of how poor the whole thing is, and how shocking the process and results, the key element of it all, including the court case is consent. I’ve had a look at the link on the GIDS page and all I can see is this:

The ethics application outlined potential risks and benefits of early pubertal suppression and consideration of different research designs.

And

Informed consent for participation was obtained from young people themselves and from a parent with parental responsibility. All young people and families were given more than 1 month between discussion of the study and risks and benefits and signing consent to participate – in practice this was always 2 months or more. The Patient Information Sheet was approved by the Research Ethics Committee as part of the application.

Does anyone have a copy of this information sheet? We’re patients for this poor excuse for a trial consented that their children would lose fertility and sexual function?

So much to unpack here. Have only briefly read this. It’s going to take some time to dig into.

It seems like a poorly written paper with very odd inclusion of information about the pressures they were under. I can imagine it surviving peer review.

I hope journalists are now enlisting the expertise of unconnected Statisticians and
Psychologists for comment.

I would also like to hear from a clinical trials expert. This should be a registered clinical trial. Maybe it’s published in this paper but should be elsewhere.. where is the trial protocol?

It seems to me they might be in breach of their own trial and trial regulations, if after one year some of the criteria were worse (suicide scores). Is this correct? I haven’t read the paper through yet. I’ve just seen some of you comment about it on here.

In any other trial, if the experimental drug was shown to lead to a worsening of outcomes at any point, the trial should immediately be halted and reported to the regulators.

Critical question: did they breach their own trial protocol guidelines on safety and report increased suicide measures to the regulator as a Serious Adverse Event ??

I can imagine it surviving peer review = I can’t imagine it surviving peer review.

@sultanasofa

I spotted sentence referring to autism/ SRS. To be reported at a later date....

The Social Responsiveness Scale (SRS) was a baseline only assessment of autistic traits; these data will be analysed in the future.

How convenient.

Bayswater group analysis

twitter.com/bayswatersg/status/1337500357832957958?s=21

Unrolled thread:

twitter.com/threadreaderapp/status/1337524072528433152?s=21

Some thoughts:

1. Uncontrolled observational studies do not score high on the evidence hierarchy. However the fact that the data was collected prospectively is good.

1. Co-morbidities don't appear to have been recorded at baseline. Nor was sexuality.

1. There doesn't appear to be a hypothesis. Primary and secondary objectives and endpoints were not defined. This makes it very difficult to know where to start with the many reported measures. (aka a fishing trip). The study seems to have been started with broad aims:

1. To evaluate the benefits and risks for physical and mental health and wellbeing of midpubertal suppression in adolescents with GD
2. To add to the evidence base regarding the efficacy of GnRHa treatment for young people with GD
3. To evaluate continuation and discontinuation of GD and the continued wish for gender reassignment within this group.

However formal statistical analyses were limited to overall psychological functioning, self-harm index and bone health. Therefore these are probably the most robust measures to consider.

1. They had no funding so it's maybe understandable if the study isn't as robust as it could be

This was an unfunded study undertaken within a clinical service and we were dependent on the clinical service for data collection

1. Statistically the following is a red flag:

We made no attempt to account for missing data due to the small sample size and the likelihood of the data missing not at random.

1. This seems high for a group that is 89% white. No explanation is put forward

Eight participants (18%) had vitamin D insufficiency at baseline and were given vitamin D supplements.

Low Vit d would have affected mood. And also bones.

Sorry if it's been asked but Keira was there during this time; is her case included? And the outcome?

A comment that Webberly thinks was a good one from beneath their tweet.

We need to stop kidney dialysis as it's a certain pathway to kidney transplants. It's not just here to buy people with kidney failure time. No dialysis and teach people to accept their kidney disease

Webberly is a doctor??? Really??

One is truly a life threatening and accurately diagnosable medical condition, the other is a hard to define let alone diagnose condition that studies have shown the treatment may not save any additional lives in comparison to not having this particular treatment stream. Hmm? I think I would be very suspect of someone calling themselves an expert clinician that does not have an unbiased and questioning approach.

In fact, I’d be running a mile knowing my clinician showed such unquestioning acceptance in light of the lack of evidence that is being shown by an organization considered one of the world’s leading treatment clinics (the Tavistock) for this condition.

notbadconsidering have a look at the NHS Research Authority report of their Inquiry into complaints about the GIDS study. It mentions the Information Leaflet and that it was misleading in talking about puberty blockers giving children the equivalent of “time to think”.

It made clear that PB were given with the intention that children would be denied normal puberty and that adverse psychological effects while on PB were to be expected. This is why increased suicidal ideation, depression, etc. after going on to PB were not considered necessary to report as “adverse incidents”. (I hope I’ve remembered that correctly, it’s a while since I last read it.)

Wondering if the expectations of adverse effects also contributed to GIDS management telling staff not to contact the Trust Safeguarding Lead about their concerns? (Sonia somebody?? Currently taking the Trust to an Employment Tribunal.)

Investigation into the study 'Early pubertal suppression in a carefully selected group of adolescents with gender identity disorders'
Last updated on 14 Oct 2019

www.hra.nhs.uk/about-us/governance/feedback-raising-concerns/investigation-study-early-pubertal-suppression-carefully-selected-group-adolescents-gender-identity-disorders/

To be clear, Webberly did not post comment, but commented she thought it was a suitable analogy (in more positive words).

Sorry, feeling like a right wally now as I’ve just seen everything I mentioned was covered by news night investigation in 2019.

www.bbc.co.uk/news/health-49036145

How is the investigation by the HRA going?

Another question I have is who was on the ethics committee?

Yet another question I have is how usual is it for an uncontrolled trial using drugs which have known serious and irreversible side effects to be conducted in children??

Interesting time to land (bury) this report. As we crash out of the EU, London goes into tier 3 and shortly before Christmas.

It seems like a poorly written paper with very odd inclusion of information about the pressures they were under

The inclusion of that statement sounds like a cry for help. The Tavistock are under hugh pressure from an unnamed parent support group, anything other than affirmation and they get accused of transphobia.

Does it mention the residentials that clinicians were invited to?

I'm not sure how to understand these two things:

No change in psychological function after time on these drugs
AND
The distress that children were under/reporting before taking them

Does the "no change" mean that they continued in distress?

Thanks MoleSmokes, so much to read there too but this bit stood out:

The Committee questioned the wording on page 96 of the Young Person Information Sheet, some of the advantages/disadvantages were the same and the committee suggested that clarification should be given with the section re-written on the potential benefits and possible disadvantages of treatment

This 96+ page Young Person Information Sheet would be worth getting hold of.

But regardless, this study required children and/or their parents to consent to giving up future fertility and sexual function and even if the consent form had that on there, we know that children just cannot consent to this, and their parents shouldn’t be consenting to this for them.

No one could have adequately consented to this study.

There's something about a preliminary study that said that findings were different

I’m still not clear on what the benefits of the treatment were supposed to be, never mind if they were achieved or not...

Basically, the whole thing is a complete muddle.

I also query how much influence the parent support group had on questionaires etc.

We know that children and yp are taught what to say to get access to drugs.

I can't imagine this doesn't have an impact on true answers.

Even Jazz appears to allude to a lot of mh issues.