The Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) (GeNeSIS B9R-EW-GDFC)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Disease epidemiology
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Open label, multicenter, multi-national observational study

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  SOMATROPIN
• Medical condition to be studied:
  Growth retardation

Population studied

• Short description of the study population:
  Untreated or treated paediatric patients with growth failure and short stature.
• Age groups:
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
• Special population of interest:
  Other
• Special population of interest, other:
  Growth retarded patients
• Estimated number of subjects:
  22845

Study design details

• Main study objective:
  The goal of this study was to evaluate the safety and effectiveness of somatropin treatment in an observational setting. 2 co-primary safety objectives were used to determine the sample size necessary for the core study: 1. incidence of type 2 diabetes in somatropin-treated children,2. incidence of de novo neoplasia in somatropin treated children without a prior history of neoplastic disease
• Outcomes:
  Type 2 diabetes mellitus Neoplasia, Secondary objectives were addressed via substudies on genetic analysis, growth prediction models, SHOX deficiency, and neoplastic disease. In addition, potential factors associated with the risk of developing diabetes mellitus or alterations in glucose metabolism were examined.
• Data analysis plan:
  For key safety outcomes of mortality, diabetes and neoplasm incidence, patient history/case ascertainment required detailed review of study and corporate pharmacovigilance databases. Person-years of follow-up were calculated between first and last contacts (later of event onset, last study visit, or study summary date). Standardised mortality ratios (SMRs) and standardised incidence ratios (SIRs) were calculated using expected cases from contemporary general population registries adjusted for country, age, sex, and ethnicity (where applicable). Attainment of FH was defined by at least one of the following: closed epiphyses, height velocity <2 cm/year, or last bone age ≥14 years in girls or ≥16 years in boys. Baseline and early somatropin treatment variables that predict FH were investigated using linear regression modelling.