On 20 February 2026, the Medicines and Healthcare products Regulatory Agency (MHRA) said it had raised concerns about participant wellbeing in the PATHWAYS clinical trial and would open scientific dialogue with the sponsor. The agency said it is applying heightened scrutiny and a cautious approach given the involvement of children and young people. (gov.uk)
In a sponsor letter published alongside the statement, MHRA invites King’s College London to discuss protocol changes before any recruitment. Proposals include adding a lower age limit of 14 at consent and clarifying post‑trial arrangements to protect participants, with the regulator emphasising that strengthening safeguards comes ahead of any enrolment. (assets.publishing.service.gov.uk)
MHRA’s letter sets out for discussion an explicit inclusion criterion of ‘14 years or older at the time of consent’, citing the greater uncertainty around long‑term biological effects in younger adolescents and the need for robust exit strategies and data collection previously highlighted by the Commission on Human Medicines. (assets.publishing.service.gov.uk)
Further recommendations address safety monitoring and withdrawal rules. The agency proposes tighter bone‑health surveillance using DEXA, predefined stopping where low‑trauma fractures occur or where significant bone loss is detected, and clearer criteria for persistent vaginal bleeding to ensure swift clinical action and participant withdrawal where appropriate. (assets.publishing.service.gov.uk)
Neurological safety is also in scope: MHRA recommends using brain imaging to identify concerning changes that would trigger withdrawal, alongside closer haematological follow‑up where indicated. The regulator asks to meet the sponsor, together with the Health Research Authority, to agree amendments to the protocol. (assets.publishing.service.gov.uk)
The Department of Health and Social Care (DHSC) has confirmed that preparatory work on PATHWAYS is paused. Discussions between MHRA and King’s College London will proceed, and recruitment will not begin until the regulator’s concerns are resolved with the trial clinicians, according to DHSC’s GOV.UK statement on 20 February 2026. (gov.uk)
According to King’s College London, PATHWAYS is a randomised controlled trial comparing immediate versus delayed initiation of puberty blockers, led by the university and co‑sponsored with South London and Maudsley NHS Foundation Trust. The programme is supported through the NIHR‑NHS England National Research Collaboration Programme with independent oversight committees. (kcl.ac.uk)
This regulatory scrutiny sits alongside wider policy changes. Following advice finalised by the Commission on Human Medicines on 13 November 2024, ministers announced on 11 December 2024 that emergency restrictions on private prescribing of puberty blockers for under‑18s would be made indefinite, subject to a 2027 review. (gov.uk)
For research sponsors and NHS sites, the immediate implications are operational: prepare updated eligibility wording and consent materials, budget for additional imaging and follow‑up, and plan revised submissions to the MHRA and Research Ethics Committee. Enrolment cannot proceed until a revised protocol is agreed. (assets.publishing.service.gov.uk)