Puberty Blockers Trial

So is the big gamble here that it won’t get through the ethics committee and then the comments will save the day for everyone? Helluva risk imo

To hope they publish the comments from the committee

I don't know what is normally published about the comments made by ethics committees, but this contains some from the original Tavistock study.

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

I don’t understand how people give Gordon Guyatt credibility. SEGM made a big deal about having him at their conference and writing papers with him and then, after all that, he said it would be “unethical” NOT to have a trial: https://www.bbc.com/news/articles/clyd2qe5kkjo.amp
Having said that, SEGM are as bad as Guyatt, they don’t seem to understand why a trial is fundamentally unethical x.com/segm_ebm/status/1895125127714492834?s=46

Getting this through ethics will be interesting. Their starting point will be whether there is clinical equipoise - that there is genuine uncertainty over what treatment is best. If the committee finds that is it obvious that PBs are likely to be less effective/more harmful than the control arm, whatever that might be, then the trial cannot go ahead.

I can imagine this will not be unanimous in the committee. Committees are drawn from across society. They have lay members and professionals and they consider all types of trials, from cancer to depression. It would be very hard to nobble a committee.

They might have a sense for which committee would be likely to be more sympathetic to his study or they might try and stack the membership in advance of the trial being reviewed, but otherwise the committees are genuinely independent.

To hope they publish the comments from the committee

There remains considerable uncertainty regarding the effects of puberty blockers in individuals experiencing GD. Methodologically rigorous prospective studies are needed to understand the effects of this intervention

Agreed. I doubt Guyatt would consider the NHS study to be methodologically rigorous. It’s just a further unhelpful study that will score indifferently for GRADE, RoB etc.

@NotBadConsidering
Thank you for that, I guess my hair-trigger went off too quickly regarding the intent of a talking-head...

But I suppose my concern remains in two ways - I appreciate that we do undertake RCTs on life-threatening illnesses, but by talking about PBs in this way I feel as though it gives credibility to the idea that gender dysphoria is actually a life-threatening illness inherently. Will the risk to the patients be commensurate if there isn't an underlying threat to life that is to be treated?

With the saline example, there are well-understood mechanisms of the illness being treated, with measurable outcomes for a specific treatment. I fear that gender dysphoria as a diagnosis lacks rigour - what makes it different from other anxiety disorders, body dysmorphia, BID?

So the biases created by the presumptions of i) that there is even a distict diagnosis to be had, and ii) that the illness is life-threatening skew the basis of the trial.

Gordon Guyatt is considered the world leader/guru on Evidence-Based Medicine. His systematic review into puberty blockers was published in January. Of course it showed no evidence of benefit.

The conclusion of that paper seems to be "we are very uncertain about the effects of this treatment ".

There remains considerable uncertainty regarding the effects of puberty blockers in individuals experiencing GD. Methodologically rigorous prospective studies are needed to understand the effects of this intervention.

But I would dispute the conclusion that further studies are needed without a clear and unambiguous definition of what the condition is and why cosmetically altering the bodies of adolescents with drugs that will impact their sexual function and fertility as adults is an appropriate treatment for whatever this condition turns out to be.

This is a mental health condition with symptoms like depression. Why would anyone think that a physical treatment which results in infertility and impaired sexual function will lead to these patients having better and happier lives as adults? It seems extremely unlikely to be the case.

Gordon Guyatt is considered the world leader/guru on Evidence-Based Medicine. His systematic review into puberty blockers was published in January. Of course it showed no evidence of benefit.

https://adc.bmj.com/content/early/2025/01/29/archdischild-2024-327909

The best example of how RCTs are done on life threatening circumstances is the study done a few years ago in which paramedics were blinded to whether they were randomly giving adrenaline or saline as part of cardiac arrest resuscitation. It was thought that adrenaline might actually be making things worse. The study showed slightly better survival but more brain issues:

https://www.bbc.com/news/health-44859777.amp

So if people who are actually actively dying can be subject to a RCT, kids who don’t want their breasts to grow or their voice to change certainly can.

"Randomised trials are done in "life-threatening stuff all the time""

An interesting take from the doctor given that gender dysphoria isn't a life-threatening condition...

I feel like I tied my brain in knots thinking through the above scenario! And that I'm not making sense to myself anymore. Gender nonsense is crazy making for me :(

I had wondered this too.

I don't know how ethics committees for clinical trials work so maybe someone who does can weigh in on how likely this scenario is. If the trial in its current form doesn't get past the ethics committee can the researchers make changes to their proposal and resubmit?

A small (and probably irrational and wishful thinking) part of my brain is hoping that the ethical practitioners are playing a long game in proposing a trial in this way in the hope that it shows exactly how unethical and impossible it is and an ethics committee could not approve it, and so the trial approval process would go back and forth interminably trying to make the impossible possible and the unethical ethical, with the result that this particular can would be kicked down the road until the influence of gender zealots in public institutions has waned.

Of course this strategy and scenario would be extremely convoluted really quite bonkers but this is what gender does - nothing makes sense and nobody can speak the truth on pain of cancellation/ostracisation so we end up with all sorts of convoluted situations and double speak.

Also, the gender zealots letting go of their iron grip on public services is probably wishful thinking as well on my part, because the nature of zealous belief systems is that people don't let go of them readily.

To add to the unfortunate likelihood of this trial going ahead, Prof Gordon Guyatt, one of the pioneers in evidence-based medicine is in favour of it, as per this BBC article from December: https://www.bbc.com/news/articles/clyd2qe5kkjo

From the BBC article:
Gordon Guyatt, a professor at McMaster University in Canada, who points out that randomised trials are done in "life-threatening stuff all the time" where no-one can be sure of the long-term effects of a treatment. In his view it would be "unethical not to do it".
"With only low quality evidence, people's philosophies, their attitudes or their politics, will continue to dominate the discussion," he argues. "If we do not generate better evidence, the destructive, polarised debate will continue."

I find it a bit astonishing that people are willing to harm children to get better evidence, especially since Guyatt was the lead researcher (I think) for some recent research from McMaster university which I believe came to the same/similar conclusions as Cass. I haven't read the McMaster research so open to any corrections there!

Totally agree, so many problems.

But Dr Cass said there should be a study. She's said many things we agree with, she's tried to wrest data on the patients who've already been through this regime, and she said there should be studies. And she's far more expert than me.

What did she envisage? Is it being set up the way she would have hoped? (Two years? Surely not. The report says "with follow-up into adulthood")

It's hard to see how an ethics committee is going to be able to consistently say no to this thing, given such an eminent authority as the Cass report recommending it. And given that like most public services, if they send it back enough times it will eventually land on the desk of a true believer.

I hope I'm wrong. I think it will go ahead because of politics and I'm worried about what it will say, after only two years, with all the bias in the patient group. And, I have to assume in the medical group too, as I can't see how a GC or neutral medic could get round all the ethical issues to want to work on this.

Everything makes it a non-starter.

The lack of a clear disorder and treatment group.

The unethical nature of the treatment.

The problem with consent.

The bias of pre-conceived outcomes.

The limitations of the timeframe.

It has nothing going for it.

Genspect have published a detailed criticism of puberty blockers and their unethical experimental use on children:

https://genspect.org/wp-content/uploads/2025/03/Genspect-UK-Briefing.pdf

This trial is completely unethical. It should stopped. While I’m glad to see Our Duty come out so strong and Marcus Evans, I’m disappointed that other organisations seem pretty muted. We should be up in arms

This is what makes such a trial so difficult. Zealots have put the cart before the horse so intensely that there is a high risk of bias if they’re involved in any way. It needs to be set up and run by a non-gender clinic, and patients selected very carefully.

But informed consent is impossible, so surely that makes it a non-starter.

In a randomised controlled trial, participants are put randomly in a particular treatment group.

In a blind RCT, the participants aren’t aware of which group they’re in.

In a double blind RCT neither participants nor the observers of outcomes know which group they’re in.

Obviously with puberty blockers the latter two aren’t possible. But a RCT is possible.

There are issues to overcome (aside from the ethics of sterilising children etc):

It has to be properly random. The treating team can’t say “well this kid is more ‘insistent and persistent’ in their gender identity, they’re better off in the PBs arm.” No. It has to be completely random.

The outcomes can’t be pre-conceived. This is a massive problem. Both gender clinicians and parents/kids as two groups have the pre-conceived idea that PBs are the “right” choice already. A research clinician has to be willing to accept, and tell the participants, that there is an equal chance of all possible outcomes permutations:

Better with PBs vs therapy
Better with therapy vs PBs
No difference
Worse with PBs vs therapy
Worse with therapy vs PBs

The participant has to be consented to all possible outcomes and be willing to accept that. Any parent who says “I know my kid will be better on PBs so if she doesn’t get that, there’s no point” should be excluded.

This is what makes such a trial so difficult. Zealots have put the cart before the horse so intensely that there is a high risk of bias if they’re involved in any way. It needs to be set up and run by a non-gender clinic, and patients selected very carefully.

The usual standard is double-blind random controlled trials.

The blind bit is not possible with this treatment as the effects are obvious. This wouldn't be the first trial where that occurs. For example if administering a treatment is too onerous, or if the side effects of the potential treatment are very obvious.

The random/controlled part - might be possible, if they can find participants who are willing to participate. This is probably actually why they've said 2 years. They're not trying to get people to commit to not ever taking blockers.

The problem with the 2 years is it's just not long enough. It doesn't give children time to get used to the effects of puberty or even finish puberty (depending on the age of the cohort they're picking). It certainly doesn't give them time to reach the sort of age when many people who were determined they never wanted kids suddenly discover they do. And it doesn't give time for any long term side effects like bone density effects to really kick in. And kids who've been on blockers for two years can still be on a 'well i don't feel better yet but it's still only the first step, once I've had cross sex hormones then I'll feel like myself...' ladder.

In any decent trial the patients aren't told which group they are in. Although with puberty blockers it would become apparent well before the 2-year endpoint so the drop-out rate would be unmanageable.

Yes, I don't see how an RCT would be possible.

Only adults can give informed consent to treatment which will sterilise them and impair their sexual function.

I can't see how it would even be possible to design any kind of useful trial. Especially one that involved children. Unless they broke every rule in the book and accepted that there would be no useful data. I can't even imagine what the protocol would look like, or how one would ensure informed consent.

In any decent trial the patients aren't told which group they are in. Although with puberty blockers it would become apparent well before the 2-year endpoint so the drop-out rate would be unmanageable.

Yes - there's a reason they refused to share it - and I suspect a reason why NHS England has failed to insist and threaten to discipline for their lack of cooperation. Once it's revealed, the whole thing completely falls apart ( and the compensation costs will be in the billions)

If the evidence from the adults showed ANY positive results, it would have been given to Cass. You can bet it would be all over everywhere.

People have been asking what's happened to all the data about the 9,000 children "treated" by GIDs who have transferred to the adult clinics - the clinics who shamefully refused to share their data with Cass. According the Hannah Barnes it appears that the NHS, although committed to following this data up, has yet to begin to do so. Instead it's proposed to spend £10 million harming another tranche of children while failing to even start looking at all the data the dodgy adult clinics are concealing.

https://x.com/hannahsbee/status/1895905652045988151

The level of scandal in terms of causing harm to children is off the scale