King's College London

Two new research studies have received all necessary regulatory and ethics approvals to provide a stronger evidence base to understand how to best support young people with gender incongruence being treated in specialist NHS Children and Young People’s Gender Services and will begin recruiting participants soon.

PATHWAYS TRIAL is a carefully designed clinical trial of puberty suppression. It is open only to those accessing specialist NHS care and support for gender incongruence and co-occurring conditions, who meet the clinical criteria, and after approval by an independent expert panel. Consent from the young person’s parent or legal guardian will also be needed.

PATHWAYS CONNECT is a study of brain health comparing those receiving puberty suppression together with psychosocial and other non-medical care with those receiving psychosocial and other non-medical care alone.

Both studies are part of the larger Puberty Suppression and Transitional Healthcare with Adaptive Youth Services (PATHWAYS) study, which aims to find out how the NHS can best support children and young people attending gender services.

Professor Emily Simonoff, Professor of Child and Adolescent Psychiatry at the Institute of Psychiatry, Psychology & Neuroscience and Chief Investigator of the study, explained: “All young people attending NHS Children and Young People’s Gender Services receive a comprehensive package of assessment and support which can include a mix of paediatrics, psychological therapies, occupational therapy, communication interventions, family and school support. We are already evaluating young people’s experiences of these services in the world’s largest observational study of its kind, called PATHWAYS HORIZON.”

The PATHWAYS research study is led by King’s College London, is supported by the King’s Clinical Trials Unit, and is co-sponsored by King’s College London and the South London and Maudsley NHS Foundation Trust. NHS England has commissioned and funded the study as part of a wider research programme in partnership with the National Institute for Health and Care Research (NIHR).

The study has undergone a comprehensive review of the science by independent scientists advising NHS England and NIHR. This included independent academic peer reviewers and funding committee consideration. The new studies being launched today have now also received all necessary ethics and regulatory approvals.

The researchers estimate 226 young people could be recruited to the clinical trial over three years. The planned sample size is large enough to provide robust evidence about the comparative benefits and harms between these two groups.

PATHWAYS CONNECT is an observational study which will look at young people’s thinking and brain development, and will follow both those who are- and are not- taking puberty suppressing hormones.

The study will enable a greater understanding of whether puberty suppression has any impact on brain development. It is expected that approximately 250 young people will take part, with around 150 who are taking part in the clinical trial of puberty suppression and 100 young people accessing non-medical care and support alone.

Dr Michael Absoud, Adjunct Reader & Consultant in Paediatric Neurodisability in the Faculty of Life Sciences & Medicine and deputy chief investigator for the study, said: “Young people with gender incongruence and their families have told us that they do not have the information that they need to make informed choices about their care."

He continued: “We already have some information about the use of puberty suppressing hormones in young people, because these treatments have been given to children since the 1980s to treat early puberty. We have a good sense of the benefits and risks in this distinct context. We hope the clinical trial will give us important information about the specific use of puberty suppressing hormones to delay puberty for those with gender incongruence, including benefits and any side effects.

“Importantly, we have spent time designing the most rigorous and safest study design with significant safeguards and oversight. This includes close monitoring of risks and side effects throughout the study. We are pleased that the UK’s regulators and a research ethics committee have approved the studies, and that we will be able to begin recruiting.”

All parts of the PATHWAYS study have been designed to meet rigorous scientific and ethics standards. PATHWAYS TRIAL has been reviewed by the Medicines and Healthcare products Regulatory Agency (MHRA), who sought independent advice from the Commission on Human Medicines; and by the Health Research Authority and a Research Ethics Committee.

All PATHWAYS studies will be overseen by independent oversight boards made up of clinicians, scientists and lay members with lived experience external to the research project. They are informed by two independent lived experience advisory boards of young adults and parents.

“Clinical care should always be underpinned by robust evidence, and this study will help provide a better understanding of how to treat and care for young people with gender incongruence," Professor Simonoff added.

“We know there are ongoing societal discussions about gender transition, but this research is focused solely on informing and improving healthcare by better understanding how to support the physical and mental health of young people with gender incongruence.”

The Cass Review highlighted the lack of robust evidence for either the benefits or risks of the use of puberty suppression in gender incongruence. It recommended ‘a full programme of research should be established to look at the characteristics, interventions and outcomes of every young person presenting to the NHS gender services.

“Taken together the whole suite of PATHWAYS studies will provide a stronger evidence base to allow young people with gender incongruence and their families to make better informed decisions to give them the best wellbeing and health in the longer term,” Professor Simonoff concluded.