Supplementary Material for: An Analysis of the Clinical and Cost Effectiveness of Growth Hormone Replacement Therapy before and during Puberty: Should We Increase the Dose?

Aim: To investigate the influence of growth hormone (GH) on linear growth before and during puberty in children with GH deficiency. Methods: We analysed the relationship between pubertal growth and GH dose in a large dataset of children (n = 236) with GH deficiency using multiple linear regression and multilevel modelling with repeated measures analysis. Additionally, we examined the cost benefit of increasing doses of GH during puberty. Results: Multilevel modelling revealed a highly significant role for GH dose in the pre-pubertal period (p < 0.001), but a non-significant effect on height gain after pubertal onset (p = 0.32). Important predictors of height gain after puberty onset included gender, age at puberty and number of injections of GH/week. Cost analysis showed that in an average child use of high dose GH, at an extra EUR 5,925 (GBP 4,753/USD 7,538)/year, would produce a height gain of 0.80 cm/year (above baseline growth) pre-pubertally, compared to only 0.20 cm/year post-puberty onset. Conclusions: The influence of GH dose on height gain after puberty onset is at best a modest one. Cost analysis shows use of high doses of GH post-puberty onset has significant cost implications without providing a worthwhile gain in adult height for children with GH deficiency.

研究目的：探讨生长激素（growth hormone, GH）对生长激素缺乏症儿童青春期前及青春期期间线性生长的影响。方法：本研究纳入236名生长激素缺乏症儿童的大型数据集，采用多元线性回归结合带重复测量分析的多水平模型，分析青春期生长与生长激素剂量之间的关联；同时探讨青春期期间提高生长激素给药剂量的成本效益。结果：多水平模型分析结果显示，生长激素剂量在青春期前阶段对身高增长具有极显著的影响（p < 0.001），但在青春期启动后对身高增长的作用无统计学意义（p = 0.32）。青春期启动后身高增长的重要预测因素包括性别、青春期起始年龄以及每周生长激素注射次数。成本分析表明，对于普通患儿，青春期前使用高剂量生长激素每年额外支出5925欧元（折合4753英镑/7538美元），可使患儿年身高增长较基线增长多出0.80厘米；而青春期启动后使用高剂量生长激素仅能带来每年0.20厘米的额外身高增长。结论：生长激素剂量对青春期启动后身高增长的影响至多仅为轻度作用。成本分析结果显示，青春期启动后使用高剂量生长激素虽会产生显著的成本负担，却无法为生长激素缺乏症儿童带来成人身高方面的可观增益。