Tavistock puberty blocker study published

[PaleBlueMoonlight]

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

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

@allmywhat

or lumping the two self-harm statements together made the significant increase in one of them disappear (which strikes me as potentially dodgy.

Quoting myself. On further reflection, and to do them justice, if the increase in "I try to hurt or kill myself" was a real increase and not just a statistical fluke, then I think you would really expect it to be accompanied by an increase in "I have suicidal thoughts." I'm not a psychologist, but it seems to make good sense.

So while I do suspect them of creating this Self Harm index (lumping the two scores together) to disguise the increase that Michael Biggs highlighted - it still seems like a reasonable enough thing to do. I think I'm willing to absolve them of dodginess on this score, because I think lumping the two scores together would only work to disguise a statistical-fluke increase and wouldn't work to disguise a real effect.

They state the following in the manuscript We followed previous studies in calculating a self-harm index score to avoid multiple statistical comparisons across correlated categorical-response variables. and later Our study adopted the same psychological outcome measures as the Dutch cohort, to facilitate comparison. I agree that, given the circumstances, this seems reasonable.

I'm wary of attaching meaning to any of the data given the bigger issues of no hypotheses, no primary endpoint, no control, no attempt to adjust for missing data, and no data collection beyond start of CSH.

How....

...unsurprising.

It can't be too long before the lawsuits start coming in.

@ItsAllGoingToBeFine

The court asked for statistics on the number or proportion of young people referred by GIDS for PBs who had a diagnosis of ASD. Ms Morris said that such data was not available

I may be misreading, but it sounds as if the court asked about children with a diagnosis of ASD. The paper only assesses ASD traits

This would be my understanding - the SRS is a screening tool for ASD, not a diagnostic tool. Children identified with high scores would often be referred for full assessment.

So, if PBs aren't reversable and puberty has a window of opportunity and a person goes straight from PB to CSH for the rest of their life - are they an adult?

i mean, if puberty is a maturation process which includes maturation of thought have we created people who are permanent juveniles?

I'm trying to find an article I read once about a man who didn't take pbs for precocious puberty and the reasons given. Some of the reasons for taking them are that behaviour can be tumultuous for the child; his dad had the same condition and there was something about how his father felt that in the end it was ok (very vague memory.)

Anyway, obviously I'm wading through trans links. This rapid response debate in the BMJ about the study is fascinating and revealing.

www.bmj.com/content/366/bmj.l5647

Whilst many paediatricians prescribe ‘off-label’, halting natural puberty in gender dysphoria is entirely unrelated to previous indications. Prescribers, and psychologists who don’t prescribe, should not suggest that safety data can be transferred from triptorelin used for restoring correct timing in precocious puberty. Here, its use has many far reaching consequences so a more stringent research design was required. By gaining permission to study individuals without controls, and by not studying the whole pathway, we were never likely to learn much about the benefits or harms. Empiricism is simply not a good enough approach. Whilst RCTs might be difficult, they are not impossible, and simply have not been tried. Back in 2010, an opportunity for a UK pilot feasibility trial was missed when puberty blockers were not routine.

Quote from 21 October 2019
Richard Byng
GP and Professor in Primary Care Research
Susan Bewley, Emeritus Professor of Obstetrics and Women’s Health, Kings College London
University of Plymouth
John Bull Building, Tamar Science Park, Plymouth.

@OhLittleBoreOfWhabylon

It can't be too long before the lawsuits start coming in.

They are already in the pipeline. Solicitors have been touting for business from detransitioners for a year or so. This piss-poor paper from GIDS is Christmas come early for personal injury lawyers. It's so obvious that no proper steps were taken to monitor the effects of an experimental treatment that it will be impossible for GIDS to argue that it fulfilled its duty of care. And Keira's case has wiped out informed consent as a defence.

I'm pleased to hear that MissLucy.

Jo Bartosch wrote a great piece about her parents refusing growth hormones for her (not PBS, but a similar endocrine intervention that doesn’t have a clear clinical indication)

thecritic.co.uk/issues/july-august-2020/short-changed-by-society/?fbclid=IwAR2Ss5eb9HR_I5XVTvjtsTaeqOefizYpd1ZrH2C8uZIZesFvsBSsVQIFc1k

MissLucyEyelesbarrow
That's very interesting when you say:
They are already in the pipeline. Solicitors have been touting for business from detransitioners for a year or so. This piss-poor paper from GIDS is Christmas come early for personal injury lawyers. It's so obvious that no proper steps were taken to monitor the effects of an experimental treatment that it will be impossible for GIDS to argue that it fulfilled its duty of care. And Keira's case has wiped out informed consent as a defence

I wonder whether any of these children (or their parents) will go for the schools who have unthinkingly socially transitioned children, enabled children to access lobby groups without parental permission and ignored safeguarding standards?

I do worry that many schools will be unaware of the implications of this judgement and will be carrying on with their 'Stonewall' policies and training.

I wonder whether any of these children (or their parents) will go for the schools who have unthinkingly socially transitioned children, enabled children to access lobby groups without parental permission and ignored safeguarding standards?

I hope they do. It will focus school's minds on safeguarding and evidence very nicely.

I mean, if puberty is a maturation process which includes maturation of thought have we created people who are permanent juveniles?

I often wonder about this. Also if there could potentially be new "conditions" that arise if the use of PBs was to become more wide spread. I mean if you can go through the "wrong" puberty why not reject the idea of puberty altogether? I can imagine some sort of non-binary identity (just to make sure nobody would dare suggest it was a bonkers idea).

Eowynthewarrior

Also why was autism not properly explored before treatment given? It’s not as if a doctor is being faced with a choice of two harmless treatments for a common disease ( eg a skin infection where the only consequences of getting it wrong would be the rash doesn’t clear up and you switch treatment accordingly. How can a decision be made to give life changing potentially irreversible drugs without exhausting other avenues for diagnosis such as proper autism assessment first ? The risks snd stakes are so high surely it should have been throughly investigated? Did the children undergo any other tests to see if there were reasons for their distress ?

In terms of exploration of autism (or other diagnosis) before treatment started, the manuscript says that a full history was taken as part of the work up. Best medical practice would include an assessment for autism and other relevant history, would record this in the patient's medical notes, and take this into account when considering management. However this manuscript does not include any more details about whether this was done or not - we simply don't know.

At the first medical clinic, young people and families were seen by a senior paediatric endocrinology clinician together with a senior GIDS clinician........ A full medical history was elicited and the clinicians also reviewed a summary of the psychological history and assessment from the GIDS.

We know that a decision was taken not to record medical history in the study database. Therefore an important opportunity to quantify rates of autism and other relevant medical history in this GIDS cohort was missed.

allmywhat and sultanasofa

Thank you very much for looking into the disparity between the recording suicide measures between the preliminary report and final report.

My questions:

1. this is a clinical trial. You are supposed to plan your outcome measures and how you will calculate them in advance in the statistical plan for the trial documents. if you change the plan part way through a trial you have to issue an amendment and rationale. All very normal... the purpose is To avoid data manipulation or questions about data manipulation. I wonder whether we can get these docs?

1. Do we have the raw data? Can we see if the mean scores for these two suicide questions were statistically significantly different at the later time points??

1. Why THE HELL didn’t they report an increase in their own suicide measures to the regulator as an Serious adverse event (SAE) at 12 months??

May I ask a tangential question while we are talking about the published work. I’m not a scientist but I would like to understand research study design and process better so I can know what to trust. Is there anywhere non-scientists can read up on the type of questions we should be asking about published research? I’ve read various articles saying to look out for high quality or well designed research but I don’t know enough to know what that really means in practice.
Sorry if this is a ridiculous question, perhaps it’s like me asking a lawyer or doctor how I can understand their professional thinking better and you’ve all been studying this for years and done professional work for years in it. I hope it’s not an offensive question, its really not meant that way.

This would be my understanding - the SRS is a screening tool for ASD, not a diagnostic tool. Children identified with high scores would often be referred for full assessment.

Is there any evidence that GIDS did this before starting them on puberty blockers?

chattylion

Try

www.nihr.ac.uk/health-and-care-professionals/learning-and-support/good-clinical-practice.htm

www.hra.nhs.uk/planning-and-improving-research/

They would be the gold standard. they’re not designed for public but I think you would find the introduction sections very useful

I think what would’ve happens/is happening is that GIDS screen for ASD traits, it the score is high then they refer back to the local ASD assessment services for a recommendation for a full assessment. The local services will then decide whether to proceed with the assessment. It won’t be linked to the GIDS treatment. If the patient, or their parents don’t want an assessment then they won’t get one. Local services are stretched, waiting lists often over a year or longer.

You’ve then got the added complication of being in two systems for two different things.

With the push by vociferous voices for quicker intervention, they’re not going to wait for 1 year plus for an ASD diagnosis.

The gold standard should be that GIDS is linked to an expedited ASD assessment service. Though that will never be commissioned due to gender dysphoria now being classed as a stand alone condition even though it can be linked to some mental health conditions and ASD ridged thinking.

On bone mineral density. My reading of the methods is that they did take account of age and sex adjusted scores:

“BMD z-scores for age and birth-registered sex appropriate to this machine were calculated.[26]”

ChattyLion

You could have a browse around the ICH Guidelines. These are internationally agreed and then the corresponding signed- up regulatory agencies (US, EU, Japan, others...) incorporate them into their own guidance
www.ich.org/page/efficacy-guidelines

E6 Good Clinical Practice (GCP) is an important one

E9 Statistical Principles for Clinical Trials also addresses many of the issues we've been discussing on this thread

This guidance (as well as that of the region and countries) must be followed in order to get new drugs, and new indications, approved.

In this case no new drug licence is being sought. The drugs are being used off-label for an unlicensed indication. This in itself is not a problem, off-label prescribing is fairly common especially in children.

However had anyone sought to make treatment of gender dysphoria a licensed indication for PBs, they would have needed to generate a substantial evidence package demonstrating that the drug worked, that it had an acceptable safety profile, a favourable benefit-risk assessment and much else.

Thank you so much everything and sultana that’s very kind of you to give links.

@everythingthelighttouches

On bone mineral density. My reading of the methods is that they did take account of age and sex adjusted scores:

“BMD z-scores for age and birth-registered sex appropriate to this machine were calculated.[26]”

I read it as them having adjusted the Z scores - and I can't see how they could derive them, otherwise - but not the paired readings. It is unclear, though.

everythingthelighttouches

1) this is a clinical trial. You are supposed to plan your outcome measures and how you will calculate them in advance in the statistical plan for the trial documents. if you change the plan part way through a trial you have to issue an amendment and rationale. All very normal... the purpose is To avoid data manipulation or questions about data manipulation. I wonder whether we can get these docs?
I agree. It appears it was never a particularly rigorous trial from the outset. I suspect the initial protocol didn't go into these details.

2. Do we have the raw data? Can we see if the mean scores for these two suicide questions were statistically significantly different at the later time points??
Everything I've seen I've posted in this thread. There is a lot more about the interim data than the final data. You can probably work out the raw data from looking at the table.

3. Why THE HELL didn’t they report an increase in their own suicide measures to the regulator as an Serious adverse event (SAE) at 12 months??
Ultimately it's the decision of the investigator whether a safety signal constitutes an serious adverse event or not. I think you could make an argument that it doesn't meet the criteria below.

Serious Adverse Event (SAE)
Any untoward medical occurrence that at any dose:

• results in death,
• is life-threatening,
• requires inpatient hospitalization or prolongation of existing hospitalization,
• results in persistent or significant disability/incapacity,

or

• is a congenital anomaly/birth defect

From discussion section of the paper:

“Psychological distress and self-harm are known to increase across early adolescence. Normative data show rising YSR total problems scores with age from age 11 to 16 years in non-clinical samples from a range of countries.[29] Self-harm rates in the general population in the UK and elsewhere increase markedly with age from early to mid-adolescence, being very low in 10 year olds and peaking around age 16-17 years.[53-56] Our finding that psychological function and self-harm did not change significantly during the study is consistent with two main alternative explanations. The first is that there was no change, and that GnRHa treatment brought no measurable benefit nor harm to psychological function in these young people with GD. This is consonant with the action of GnRHa, which only stops further pubertal development and does not change the body to be more congruent with a young person’s gender identity. The second possibility is that the lack of change in an outcome that normally worsens in early adolescence may reflect a beneficial change in trajectory for that outcome, i.e. that GnRHa treatment reduced this normative worsening of problems. In the absence of a control group, we cannot distinguish between these possibilities. We aimed to use normative reference data to examine this issue. However age- and gender-standardised t-scores for ASEBA and other outcomes cannot answer this question as they cover a very broad age range (e.g. 12-18 years). We had anticipated that z-scores on the YSR available by calendar year for two comparable countries (Netherlands; Australia) might be informative however confidence intervals were too wide to draw reliable inferences.“

My translation for the lay person ( I welcome any corrections or comment):

They acknowledge that because they didn’t run a controlled study, they don’t know whether the drug had any impact at all on psychological distress and self harm.

They planned to compare the data to known data for the general population however they were unable to.

I would like to suggest that their chosen method of measuring this data (using median scores and combining two separate questionnaire answers) was always going to lead to an issue comparing to the published data for the general population.

WHY did they test an experimental treatment on young children, if not to reduce those children’s’ psychological distress??? They failed.

The one thing in clinical trials which is worse than a bad outcome, is an outcome which you can’t interpret or explain.

They failed.