{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:00:36Z","timestamp":1790938836718,"version":"4.1.0"},"reference-count":27,"publisher":"Becaris Publishing Limited","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Comp. Eff. Res."],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    <jats:bold>Aim:<\/jats:bold>\n                    Growth hormone deficiency (GHD) in pediatric patients is characterized by impaired growth and reduced quality of life. Recombinant human growth hormone therapy requires consistent daily administration, yet adherence remains challenging. Electronic injection devices with adherence monitoring, like Easypod\n                    <jats:sup>\u00ae<\/jats:sup>\n                    , may support more consistent administration and enable more accurate assessment of treatment response. This study evaluated the cost-effectiveness of somatropin administered via a connected injection device (EasyPod) compared with nonconnected devices in pediatric patients with GHD in Spain.\n                    <jats:bold>Materials &amp; methods:<\/jats:bold>\n                    A microsimulation model simulated 10,000 pediatric patients aged 2\u201313\u00a0years and incorporated adherence-dependent growth response, treatment discontinuation, costs and utilities. Outcomes included final height, height gain, cost per cm gained and incremental cost per quality-adjusted life year gained. Scenario and sensitivity analyses assessed the impact of parameter and structural uncertainty.\n                    <jats:bold>Results:<\/jats:bold>\n                    Easypod was associated with greater height gains than nonconnected devices. Projected final height at bone maturation was 163.04\u00a0cm with Easypod versus 159.21\u00a0cm with nonconnected devices, an incremental gain of 3.83\u00a0cm. Cost per cm gained was \u20ac2625 with Easypod and \u20ac3158 with nonconnected devices, a saving of \u20ac534 per cm. The incremental cost per quality-adjusted life year gained was \u20ac27,200 within Spain\u2019s willingness-to-pay threshold. Scenario and sensitivity analyses showed consistent results.\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    In this model-based analysis, Easypod was associated with improved growth outcomes and was cost-effective compared with nonconnected devices in pediatric GHD patients in Spain. Continuous adherence monitoring may support treatment optimization and more efficient healthcare resource utilization.\n                  <\/jats:p>","DOI":"10.57264\/cer-2026-0093","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:06:42Z","timestamp":1789042002000},"source":"Crossref","is-referenced-by-count":0,"title":["Cost-effectiveness of a connected injection device for daily somatropin therapy in pediatric growth hormone deficiency in Spain: a scenario-based microsimulation analysis using real-world data"],"prefix":"10.57264","volume":"15","author":[{"given":"Antonio de","family":"Arriba","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology Unit, Hospital Miguel Servet, Zaragoza University, Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Roeder","sequence":"additional","affiliation":[{"name":"AESARA Europe, Zug, Switzerland &amp; Merck Healthcare KGaA, Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Nivelle","sequence":"additional","affiliation":[{"name":"SHE, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula van","family":"Dommelen","sequence":"additional","affiliation":[{"name":"Department of Child Health, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose J","family":"Alc\u00f3n S\u00e1ez","sequence":"additional","affiliation":[{"name":"Consorcio Hospital General Universitario de Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Latre","family":"Gorbe","sequence":"additional","affiliation":[{"name":"Hospital Sant Joan de D\u00e9u, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi de","family":"los Santos Real","sequence":"additional","affiliation":[{"name":"Merck, S.L.U., Madrid, Spain (an affiliate of Merck KGaA)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"S\u00e1nchez-Collado","sequence":"additional","affiliation":[{"name":"Merck, S.L.U., Madrid, Spain (an affiliate of Merck KGaA)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falko","family":"Boehm","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Masseria","sequence":"additional","affiliation":[{"name":"AESARA Europe, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"36897","reference":[{"issue":"6","key":"e_1_3_8_3_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1159\/000452150","article-title":"Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency","volume":"86","author":"Grimberg A","year":"2016","unstructured":"Grimberg A, DiVall SA, Polychronakos C ; Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm. Res. Paediatr. 86(6), 361\u2013397 (2016).","journal-title":"Horm. Res. Paediatr."},{"issue":"3","key":"e_1_3_8_4_2","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1210\/jc.2009-1471","article-title":"Observed and predicted growth responses in prepubertal children with growth disorders: guidance of growth hormone treatment by empirical variables","volume":"95","author":"Ranke MB","year":"2010","unstructured":"Ranke MB, Lindberg A, KIGS International Board. Observed and predicted growth responses in prepubertal children with growth disorders: guidance of growth hormone treatment by empirical variables. J. Clin. Endocrinol. Metab. 95(3), 1229\u20131237 (2010).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_3_8_5_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ghir.2015.12.002","article-title":"Variability in adherence to rhGH treatment: socioeconomic causes and effect on children's growth","volume":"26","author":"De Pedro S","year":"2016","unstructured":"De Pedro S, Murillo M, Salinas I Variability in adherence to rhGH treatment: socioeconomic causes and effect on children's growth. Growth Horm. IGF Res. 26, 32\u201335 (2016).","journal-title":"Growth Horm. IGF Res."},{"issue":"2","key":"e_1_3_8_6_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1159\/000341151","article-title":"Quality of life in children and adolescents with growth hormone deficiency: association with growth hormone treatment","volume":"78","author":"Geisler A","year":"2012","unstructured":"Geisler A, Lass N, Reinsch N Quality of life in children and adolescents with growth hormone deficiency: association with growth hormone treatment. Horm. Res. Paediatr. 78(2), 94\u201399 (2012).","journal-title":"Horm. Res. Paediatr."},{"issue":"10","key":"e_1_3_8_7_2","doi-asserted-by":"crossref","first-page":"e0206009","DOI":"10.1371\/journal.pone.0206009","article-title":"Effect of adherence to growth hormone treatment on 0\u20132-year catch-up growth in children with growth hormone deficiency","volume":"13","author":"van Dommelen P","year":"2017","unstructured":"van Dommelen P, Koledova E, Wit JM Effect of adherence to growth hormone treatment on 0\u20132-year catch-up growth in children with growth hormone deficiency. PLOS One 13(10), e0206009 (2017).","journal-title":"PLOS One"},{"key":"e_1_3_8_8_2","doi-asserted-by":"crossref","first-page":"795224","DOI":"10.3389\/fendo.2022.795224","article-title":"Treatment adherence to injectable treatments in pediatric growth hormone deficiency compared with injectable treatments in other chronic pediatric conditions: a systematic literature review","volume":"13","author":"Gomez R","year":"2022","unstructured":"Gomez R, Ahmed SF, Maghnie M, Li D, Tanaka T, Miller BS. Treatment adherence to injectable treatments in pediatric growth hormone deficiency compared with injectable treatments in other chronic pediatric conditions: a systematic literature review. Front. Endocrinol. (Lausanne) 13, 795224 (2022).","journal-title":"Front. Endocrinol. 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Outcomes Res."},{"key":"e_1_3_8_11_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.61679\/1704091107","article-title":"Cost-consequence analysis for recombinant human growth hormone treatment administered via different devices in children in Spain","volume":"17","author":"Alc\u00f3n S\u00e1ez J","year":"2022","unstructured":"Alc\u00f3n S\u00e1ez J, Mu\u00f1oz A, Gorbe C, P\u00e9rez-Carbonell L, Villalobos T, Mor\u00e1n O. Cost-consequence analysis for recombinant human growth hormone treatment administered via different devices in children in Spain. 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