I should have posted the conclusions to those NICE Evidence Reviews commissioned by Cass!
Evidence review: Gonadotrophin releasing hormone analogues for children and adolescents with gender dysphoria
Conclusion
The results of the studies that reported impact on the critical outcomes of gender dysphoria and mental health (depression, anger and anxiety), and the important outcomes of body image and psychosocial impact (global and psychosocial functioning), in children and adolescents with gender dysphoria are of very low certainty using modified GRADE. They suggest little change with GnRH analogues from baseline to follow-up.
Studies that found differences in outcomes could represent changes that are either of questionable clinical value, or the studies themselves are not reliable and changes could be due to confounding, bias or chance. It is plausible, however, that a lack of difference in scores from baseline to follow-up is the effect of GnRH analogues in children and adolescents with gender dysphoria, in whom the development of secondary sexual characteristics might be expected to be associated with an increased impact on gender dysphoria, depression, anxiety, anger and distress over time without treatment. The study by de Vries et al. 2011 reported statistically significant reductions in the Child Behaviour Checklist (CBCL) and Youth Self-Report (YSR) scores from baseline to follow up, which include measures of distress. As the aim of GnRH analogues is to reduce distress caused by the development of secondary sexual characteristics, this may be an important finding. However, as the studies all lack appropriate controls who were not receiving GnRH analogues, any positive changes could be a regression to mean.
The results of the studies that reported bone density outcomes suggest that GnRH analogues may reduce the expected increase in bone density (which is expected during puberty). However, as the studies themselves are not reliable, the results could be due to confounding, bias or chance. While controlled trials may not be possible, comparative studies are needed to understand this association and whether the effects of GnRH analogues on bone density are seen after they are stopped. All the studies that reported safety outcomes provided very low certainty evidence.
No cost-effectiveness evidence was found to determine whether or not GnRH analogues are cost-effective for children and adolescents with gender dysphoria.
The results of the studies that reported outcomes for subgroups of children and adolescents with gender dysphoria, suggest there may be differences between sex assigned at birth males (transfemales) and sex assigned at birth females (transmales).
https://cass.independent-review.uk/wp-content/uploads/2022/09/20220726_Evidence-review_GnRH-analogues_For-upload_Final.pdf
Evidence review: Gender-affirming hormones for children and adolescents with gender dysphoria
Conclusion
Any potential benefits of gender-affirming hormones must be weighed against the largely unknown long-term safety profile of these treatments in children and adolescents with gender dysphoria.
Results from 5 uncontrolled, observational studies suggest that, in children and adolescents with gender dysphoria, gender-affirming hormones are likely to improve symptoms of gender dysphoria, and may also improve depression, anxiety, quality of life, suicidality, and psychosocial functioning. The impact of treatment on body image is unclear. All results were of very low certainty using modified GRADE.
Safety outcomes were reported in 5 observational studies. Statistically significant increases in some measures of bone density were seen following treatment with gender-affirming hormones, although results varied by bone region (lumber spine versus femoral neck) and by population (transfemales versus transmales). However, z-scores suggest that bone density remained lower in transfemales and transmales compared with an equivalent cisgender population. Results from 1 study of gender-affirming hormones started during adolescence reported statistically significant increases in blood pressure and body mass index, and worsening of the lipid profile (in transmales) at age 22 years, although longer term studies that report on cardiovascular event rates are required. Adverse events and discontinuation rates associated with gender-affirming hormones were only reported in 1 study, and no conclusions can be made on these outcomes.
This review did not identify sub-groups of patients who may benefit more from gender- affirming hormones.
No cost-effectiveness evidence was found to determine whether gender-affirming hormones are a cost-effective treatment for children and adolescents with gender dysphoria.
https://cass.independent-review.uk/wp-content/uploads/2022/09/20220726_Evidence-review_Gender-affirming-hormones_For-upload_Final.pdf
My bolding in the above.
Assessing cost-effectiveness would be a challenge because puberty blockers and cross-sex hormones for kids are only some of the first steps on the medical pathway and the cost-effectiveness of the whole pathway should be considered to put them into context. This should include iatrogenic outcomes (harms from medical intervention) and "technology abandonment", ie. detransitioners.
NICE - 7 Assessing cost effectiveness
Health economics is about improving the health of the population through the efficient use of resources, so it necessarily applies at all levels, including individual clinical decisions. Clinicians already take resources and value for money into account when making clinical decisions; the incorporation of good-quality health-economic evidence into clinical guidelines can help to make this more consistent.
The Guideline Development Group (GDG) is required to make decisions based on the best available evidence of both clinical and cost effectiveness. This chapter describes the role of the health economist in the development of NICE clinical guidelines, and suggests possible approaches to considering economic evidence as part of the guideline development process. It also sets out the principles for conducting new economic modelling studies if there is insufficient evidence in the literature to assess the cost effectiveness of key interventions or services.
Guideline recommendations should be based on the estimated costs of the interventions or services in relation to their expected health benefits (that is, their 'cost effectiveness'), rather than on the total cost or resource impact of implementing them. Thus, if the evidence suggests that an intervention or service provides significant health benefits at an acceptable cost per patient treated, it should be recommended even if it would be expensive to implement across the whole population.
When implementing a guideline's recommendations, commissioners and trusts also need to know the resource and cost implications for their organisations. NICE undertakes a separate, but parallel, cost-impact analysis. This analysis is usually developed by the NICE costing analyst during the consultation period of the clinical guideline. Costing tools are published at the same time as the guideline, to allow organisations to estimate implementation costs
More at:
https://www.nice.org.uk/process/pmg6/chapter/assessing-cost-effectiveness
QALYs and their role in the NICE decision-making process
April 2017 - Prescriber
In the third article in our series on NICE guidance, we discuss Quality-Adjusted Life Years (QALYs), a key calculation used by NICE when assessing the cost. effectiveness of new treatments.
https://wchh.onlinelibrary.wiley.com/doi/pdf/10.1002/psb.1562