UK clinical trial into puberty blockers paused after medicines regulator raises concerns

A clinical trial into puberty blockers for children has been paused after the medicines regulator warned it should have a minimum age limit of 14 because of the “unquantified risk” of “long-term biological harms”.Discussions between the Medicines and Healthcare products Regulatory Agency (MHRA) and the trial sponsor, King’s College London, will begin next week to discuss the wellbeing concerns, the Department of Health and Social Care (DHSC) said on Friday evening.The Pathways clinical trial will not begin to recruit until the issues have been resolved, it added.The trial was announced after a recommendation by the Cass review into children’s gender care, which concluded that the quality of research claiming to show the benefits of such medication for youngsters with gender dysphoria was “poor”.Dr Hilary Cass, who led that review, has previously said her report “uncovered a very weak evidence base” for the benefits of puberty blockers for children and young people with gender dysphoria, but “given that there are clinicians, children and families who believe passionately in the beneficial effects, a trial was the only way forward to make sense of this”.A DHSC spokesperson said on Friday: “We have always been clear about the red lines regarding this trial – ensuring the safety and wellbeing of the children and young people involved and always being led by the clinical evidence.“The MHRA has now raised new concerns – directly related to the wellbeing of children and young people – and scientific dialogue will now follow with the trial sponsor.“As the evidence is now being interrogated by clinicians, preparations for the trial have been paused while the MHRA and clinical leaders work through these concerns.“This trial will only be allowed to go ahead if the expert scientific and clinical evidence and advice conclude it is both safe and necessary.“The safety and wellbeing of children and young people have always been the driving consideration in every decision we have made regarding this trial and always will be.”A spokesperson for King’s College London said: “The wellbeing and health of young people with gender incongruence and their families has been, and will remain, our priority, and we will continue to 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.“That rigour and ongoing scientific discussion is important for any clinical trial, particularly one as complex as Pathways, which aims to build an evidence base that can help young people and clinicians to make better-informed decisions in the future.”In November, the Guardian reported that the clinical study planned to recruit an estimated 226 young people over the next three years.The youngest participants were expected to be 10 to 11 for biological females and 11 to 12 for biological males, although the team said at the time the rigorous selection process meant participants would probably be older.The MHRA has now expressed concern in a letter about the current age limit of the trial, asking for it to be raised to 14 from 10.The letter said: “Since potentially significant and, as yet, unquantified risk of long-term biological harms is present to participants and biological safety has not been definitively demonstrated in this proposed cohort, at the very least, there should be a graded/stepwise approach starting with those aged 14 as the lower limit of eligibility.“Future trials may consider lowering the threshold depending on the findings of the initial trial.”The paused trial was one of two studies that were announced to investigate the impact of puberty blockers.The Cass review in 2024 had recommended a ban on the medications. NHS England subsequently announced children with gender dysphoria would no longer receive puberty blockers as routine practice, with their use confined to research settings.Sir Jonathan Montgomery, professor of health care law at University College London, said: “The letter to the investigators is clear that the discussions are intended to strengthen the protocol, not to stop the trial.“The letter also states that these are scientific issues and not a result of legal action.“The focus here is on safety, as it should be. This pause shows the regulatory process working properly and in the interests of participants.”