PATHWAYS trial of puberty blockers for transgender youth: Where is the protocol?

The UK is poised to soon launch a landmark trial of puberty blockers for transgender youth to “to find out how the [National Health Service] can best support children and young people with gender incongruence”.

The trial has already been funded with public money and has now reportedly been submitted for ethics review.

Refusal to release the trial protocol

The Health Research Authority (HRA), the central body overseeing ethics approvals for clinical trials in the UK, has refused to make the trial protocol public at this stage, a Freedom of Information request response shared with TranspariMED by a campaigner shows.

According to the HRA:

“In this instance, we have concluded that the public interest in withholding the information until its planned publication, combined with the likelihood of prejudice, outweighs the public interest in immediate disclosure.”

The HRA’s full reasoning is set out in their response letter, reproduced further below.

What is known about this trial?

Currently, there is limited information publicly available about the design of trial, which forms part of a larger study.

According to a webpage put up by the trial’s sponsor, King’s College London:

“PATHWAYS TRIAL focusses on the effects of puberty suppressing hormones on young people’s physical, social and emotional well-being. It involves young people who want to delay puberty and whose parents and Gender Service agree with this treatment option…”

“More information about the study will be shared when the study has received regulatory and ethics approvals.”

The UK public research funder NIHR’s website states that:

“PATHWAYS Trial focusses on the effects of GnRHa on young people’s physical, social and emotional well-being. It involves young people who want to delay puberty and whose parents and Gender Service agree with this treatment option. Everyone taking part will be followed for two years during the trial, with regular checks on their physical, social and emotional well-being.”

Prepare for public shouting matches

Transgender medicine has become a culture war hot button topic. Whatever the actual trial design, there will be plenty of public shouting matches when the protocol is released.

(Note: TranspariMED has never taken any position on medical issues beyond advocating for greater transparency in clinical trials. We prefer to leave such debates to players with genuine expertise in the topics at stake.)

Keeping the trial protocol under wraps until ethics approval has been obtained may postpone these inevitable shouting matches, but will do nothing to eliminate them.

Secrecy is not in the public benefit

Transgender youth, experts and the public have a strong interest in the protocol being released prior to ethics approval, for multiple reasons:

First, external review and criticism by a large number of experts may help the researchers to further improve the protocol. Currently available information does not reveal key trial features such as inclusion criteria, treatments and controls, and endpoints. The scientific process benefits from intense scrutiny and informed debate.

Second, once ethics approval has been received, the trial will presumably go ahead as currently planned regardless of expert critiques. Any scientific discussion of the protocol at that stage will be purely academic from the perspective of trial participants.

Third, open discussion and possible modifications of the protocol may help to bring some experts with competing views closer together and jointly agree to accept – in advance – the outcomes of this trial as definitive. If that does not happen, chances are high that the moment the trial results are released, large numbers of experts will demand a second, ‘more robust’ trial. Multiple sequential trials run contrary to the interests of transgender youth.

Fourth, the UK is a democracy. Unless there is a compelling reason not to disclose the (draft) design of a publicly funded study, by default the (draft) study design should be accessible to the public.

Fifth, this is not an urgent emergency. The initial Covid treatment trials had to be designed in a hurry, leaving no room for open debate. In this case, it seems appropriate to allow a few months of open debate before settling on the final trial design.

Can transparency really improve science?

While the above arguments may seem naïve – since when do culture warriors on either side care about evidence? – experiences during the recent pandemic provide some hope.

For example, early during Covid, against a backdrop of lack of robust evidence, there was plenty of culture war screaming about whether or not hydroxychloroquine benefits hospitalised patients. Eventually, very large and well-designed trials conclusively settled that question. Medical practice has adapted accordingly, benefiting all patients with Covid. The topic is now closed.

Conversely, also during Covid, there was a paucity of robust studies into non-pharmaceutical interventions such as face masks and social distancing, leaving the evidence base contested. During the next pandemic, all these debates are almost certain to resurface, and public health decision-makers will again have to fly in the dark.

What should be done?

Sadly, the HRA’s refusal to make this trial protocol public is unsurprising. This is simply how science usually works today.

Sponsor King’s College, funder NIHR and the HRA are stellar performers in other aspects of clinical trial transparency.

However, there are better ways to generate robust evidence and settle contentious scientific debates.

For example, designing the PATHWAYS trial protocol would seem a perfect candidate for the adversarial collaboration process, where experts from opposing camps come together to jointly design a study that can answer a hotly contested scientific question.

Also, the PATHWAYS study results could be published as a Registered Report. Under this model, the protocol is peer reviewed before the study takes place, enabling critical feedback from experts before the ethics approval horse has bolted. (Note that the current protocol has likely already been reviewed by many experts external to the study – but as always in science, even more scrutiny would be even better.)

For now, the campaigner mentioned above plans to request an internal review by the HRA into its decision not to release the PATHWAYS protocol. In parallel, TranspariMED has filed a separate Freedom of Information request with the study’s funder NIHR for the protocol.

TranspariMED will make the PATHWAYS trial protocol publicly available on this blog if and when it is released.

At the same time, TranspariMED will not comment on the appropriateness or robustness of the research design – as always, we will leave that debate to genuine experts in the field.

HRA rationale for not releasing the study protocol

Image below: Screenshots of HRA email dated 23 October 2025 explaining HRA’s decision not to release the PATHWAYS study protocol in response to a Freedom of Information request.