Illustration by Gary Waters / Ikon Images

The proposed NHS-backed “Pathways” puberty blocker trial “could not have received more oversight and scrutiny”, the Health Secretary, Wes Streeting, told parliamentary colleagues in January. It had gone through “rigorous rounds of scientific, clinical, ethical and regulatory review”. How, then, to make sense of the U-turn from the Medicines and Healthcare Products Regulatory Agency (MHRA) on 20 February? The medicines regulator had initially given its approval for Pathways, which is being led by researchers from King’s College London (KCL). In a letter to KCL, the MHRA raised significant safety and ethical concerns, prompting the trial to be paused.

On one level, this suspension can be seen as scientific scrutiny working well. After the trial was announced in November 2025, hundreds of clinicians voiced “grave disquiet” about the trial’s design. I have scrutinised the trial’s documentation and asked, in the New Statesman, whether participants are being told enough about the balance of risks and benefits. Perhaps the MHRA has listened.

But it is also pertinent to ask why the regulator approved a study it now says risks sterilising children, damaging their bones and impairing their cognition. Everything the MHRA appears to now be concerned about was known at the time of approval. The true reason behind the regulator’s actions is as yet unclear. 

Hilary Cass, whose four-year review of children’s gender services in England led to the trial, has suggested in an interview with the Observer that the decision to pause it seems “political”. Other sources with connections to youth gender care have pointed out to me that the MHRA’s actions coincide with the introduction of a new role at the regulator in January: chief medical and scientific officer. Their remit is to “oversee the MHRA’s scientific, research and innovation activities”.

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The MHRA’s letter to KCL suggests its intervention is unconnected to a legal challenge that was launched in February, which aims to stop the trial going ahead altogether. Indeed, the regulator says that its consideration of the legal case will determine whether “there are any further matters which impinge upon safety or efficacy that should also be considered”.

The legal papers calling for the trial to be scrapped show that in late summer 2025 the MHRA set out 19 grounds for not accepting the KCL team’s research. Another public body, the Commission on Human Medicines, which advises ministers on the safety, efficacy and quality of drugs, agreed with the MHRA. The KCL trial team responded to the regulator’s grounds for non-acceptance on 9 October; their letter, which has been made public, includes the MHRA’s objections.

Among these were concerns that some of the language in the proposed criteria for subjects’ inclusion in the trial was “open to subjective interpretation”; that more clarity was needed on the dosing of drugs; that additional exclusion criteria were required; and that more safety monitoring was needed. Most significantly, the MHRA argued that the study’s follow-up period for the children taking part was “inadequate to assess the long-term benefits and risks” of suppressing puberty in this group of children and young people.

“Identified risks include but [are] not limited to, effects on fertility preservation, bone mineral accrual, fracture risk, cognitive development and sexual function, which require monitoring,” the MHRA said. It pointed out that “many of these outcomes will only become measurable in adulthood” and therefore necessitated “a follow-up for a period of up to 20 years or until the participant reaches the end of physical maturation (whichever is shorter)”.

Ultimately, the trial’s follow-up period was not extended. The regulator accepted KCL’s response that follow-up into adulthood would occur through the NHS Register, which children would be encouraged to join. This, the trial team said, would “provide passively collected long-term data into adult life that includes long-term safety surveillance”.

The MHRA’s late intervention raises questions about how rigorous the regulatory and ethical approval process for clinical trials really is. Any research involving the NHS must also be approved via an independent research ethics committee (REC). These committees are staffed by volunteers, at least a third of whom must be lay people, with no background in healthcare. The committee charged with approving the Pathways trial met three times. Nine of its 12 members attended the first meeting, in September 2025 (seven are needed for it to be quorate). A subcommittee of five constituted the second. When approval was granted at the third meeting on 6 November, just three members were present. Only one person went to all three meetings.

People who have previously sat on RECs tell me this scenario is not necessarily out of the ordinary. Decisions are often made by smaller subcommittees, after the full committee has met. According to the policy document that guides the function of ethics committees, a REC is also not responsible for considering “the quality of the science” of the research it is considering. That is the responsibility of a study’s sponsor, in this case KCL.

This seems like a flaw in the system. The only source of information available to the REC is the institution that seeks to carry out research. The ethics committee is not obliged to consult more widely. In this case, the study has an eminent sponsor, KCL, and a well-respected lead researcher. But researchers, quite understandably, want their projects to go ahead.

Official minutes of a meeting of NHS England’s children’s Gender Dysphoria Research Oversight Board from March 2024, seen by the New Statesman, show the trial’s chief investigator Emily Simonoff’s enthusiasm for it. The minutes state that the final Cass Report is “likely to recommend that there should also be a formal evaluation of non-medical interventions” as a way of helping children experiencing gender-related distress. “While members were supportive of the proposition,” the minutes say, “Simonoff’s view was that the group’s efforts should be focused on establishing the puberty suppressing hormones study before reaching to other elements of the pathway.”

The scrutiny process for clinical trials is often not as robust as the public might believe. But it also seems that in this case, the ethics committee may have not followed the regulations. While decision-making can be delegated to a subcommittee, according to the official document dictating REC governance, this should be for “proposals that present no material issues of research ethics”. A trial that carries risks to children’s bones, cognitive development and future fertility would therefore seem to warrant the attention of a full committee.

A spokesperson for the Health Research Authority (HRA), which oversees and manages the work of RECs, said that the regulations allowed a committee’s final opinion to be delegated when it was seeking “information further to earlier review in full committee”. Where research involves children under 16,  RECs are also required to  “obtain advice before giving its [ethical] opinion”. In this case, the HRA says, the committee included a member with professional expertise in paediatric care, so outside involvement wasn’t required.

This individual, a paediatric intensive care consultant, did not attend any of the committee’s three meetings, but provided “expert comment” to their fellow members before the proposal was considered. (The HRA say this approach is regularly used to ensure REC meetings can proceed promptly in scenarios where not all members are available.) In this case, the comments provided stretch to a little over 200 words and consists of bullet points. Several of the reflections on the KCL trial listed as “positives” by the consultant have now been called into question by the MHRA’s intervention.

The legal challenge to the trial, mounted by a former patient, a psychotherapist and concerned parents of gender-distressed children, claims that the HRA “actively withheld outside advice from the REC”. Two groups of doctors wrote to the HRA setting out “various highly relevant concerns and questions, none of which were passed to the REC”, the submission to the court contends. The New Statesman has seen both letters. They raised concerns that the anticipated benefits of the trial did not justify the risks, that there were alternative sources of data or potential interventions that could be carried out before a trial, and that there was risk of serious and irreversible harm that could not be captured by the proposed follow-up.

One of these letters was not shared with the REC by the HRA at all. The other was passed to the REC’s chair, but only after the one meeting that involved the full committee had already taken place. Those seeking to stop the trial in court argue that this material “was unreasonably and unjustifiably withheld from the REC”, denying members the opportunity to “evaluate its significance (or otherwise) for themselves”.

An HRA spokesperson said that it was “not uncommon” for third parties to request that their concerns be considered and that it took all such concerns seriously. However, “to protect the integrity and independence of the REC review process”, the HRA reviewed everything first “to establish whether it raises new information pertinent to the REC review that should have been accounted for”. In this instance the HRA judged that the submission from KCL contained all the necessary information and there was “no basis” for the letters to be referred to the REC.

Discussions between the MHRA and KCL on how to move forward with the trial are now underway. A KCL spokesperson said that the health of young people remains their priority and that the trial team will “work with the MHRA to support their further review of the trial, which has been designed by world-leading academics with scientific rigour at its core”. Any changes to the study will have to be reviewed and approved again by the REC. Streeting has said it will “only be allowed to go ahead if the expert scientific and clinical evidence and advice conclude it is safe to do so”.

Whether or not the Pathways trial goes ahead, this episode raises serious questions about whether the systems we use to ensure research is safe and ethical can always be relied upon.

[Further reading: England’s maternity system not working for anyone, review says]

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