The Department of Health and Social Care confirmed on 20 February 2026 that preliminary work on the PATHWAYS clinical trial has been paused while new concerns from the Medicines and Healthcare products Regulatory Agency are addressed. In a separate note the same day, MHRA said it had raised issues related to participant wellbeing and published its letter to the sponsor, King’s College London. (gov.uk)
MHRA’s letter invites the sponsor to discuss targeted protocol amendments. It proposes a minimum enrolment age of 14 and a stepwise start with older participants first, citing unquantified long‑term biological risks and the extended bridging period that very young recruits would face before age 16. (assets.publishing.service.gov.uk)
The agency also sets out stronger safety monitoring and explicit withdrawal criteria. Examples include bone health checks assessed by DEXA at around 12 months and discontinuation where a low‑trauma long‑bone fracture suggests systemic fragility, alongside criteria for persistent vaginal bleeding beyond two weeks and for adverse changes on functional MRI. Consent materials should explain potential impacts on fertility in clear terms. (assets.publishing.service.gov.uk)
The Health Research Authority states the study was approved via the combined review process and that, because it is paused, a Research Ethics Committee will review any amendments before any restart. DHSC has added that recruitment will not begin until the regulator’s concerns are resolved with the clinical team. (hra.nhs.uk)
The pause sits within a tighter national framework on puberty‑suppressing hormones. Emergency restrictions were introduced on 29 May 2024, extended on 22 August 2024, and made indefinite on 11 December 2024 with a review in 2027, following advice from the Commission on Human Medicines. Access outside research remains prohibited for under‑18s. (gov.uk)
King’s College London documentation describes PATHWAYS as a randomised controlled trial comparing an immediate‑start group with a 12‑month delayed‑start group. The study is led by King’s College London, co‑sponsored with South London and Maudsley NHS Foundation Trust, and funded through the National Research Collaboration Programme, a partnership between NHS England and NIHR. (kcl.ac.uk)
The Commission on Human Medicines’ Recommendation 7 requires a clear exit strategy for any continuation of GnRH agonists after participants leave the trial, with ongoing data collection on efficacy and safety. That requirement will need to be reflected in any revised PATHWAYS protocol and supporting documentation. (gov.uk)
Policy Wire analysis: trial sites should prepare for updated consent language, reinforced bone‑health surveillance and access to neuroimaging, reflecting the regulator’s proposals. In practice, this includes DEXA capability at baseline and around 12 months and predefined stopping rules where bleeding, fracture or imaging criteria are met. (assets.publishing.service.gov.uk)
For families, today’s position is unchanged by the pause: new prescriptions of puberty‑suppressing hormones for gender incongruence remain prohibited outside research, while licensed use for other conditions (such as precocious puberty) is unaffected. CHM also emphasises enhanced mental health and wellbeing support for children and young people. (gov.uk)
Next steps are procedural. MHRA will open scientific dialogue with the sponsor; any agreed changes will be submitted as a substantial amendment; the Research Ethics Committee will reassess; and recruitment can only open once regulatory and ethics approvals are in place. Further updates are expected when those processes conclude. (gov.uk)