CAN-SG supports safe and meaningful research into gender-related distress in childhood. We believe PATHWAYS Puberty Blocker Trial is neither safe nor will it provide meaningful evidence for children and families. The protocol has not answered any of our concerns about the ethics of this trial. UK law governing research, derived from European law and the Declaration of Helsinki says that research on children should not disrupt their normal stages of development without good reason. There is no good reason for the use of PBs. There is no sound scientific rationale for puberty suppression improving lasting health for children with gender-related distress, and therefore no sound basis for a comparative trial. Other research questions about the causes of gender-related distress, and about non-medical treatment and support, should be addressed prior to subjecting children to the significant risks of puberty suppression. The trial design is incapable of answering the important questions about risk that have been raised – to cognitive function, bone health, fertility and long term health. It is unethical as it will be exposing children to risk for no clear benefit. The research will not study the real-world use of puberty blockers which is as a precursor to cross-sex hormones, with about 95% of children on PBs going on to CSH. This combination brings in additional serious risks that will not be studied in this research, yet will be real risks faced by the children being given PBs. As it will be parents who have to give consent because it is for children under 16 they will have to consent to possible harm to their child’s future fertility. It is difficult to understand how any parent could consent to that.