Growth Hormone (GH) Deficiency, Non-GH-deficient Growth Disorders, Short Stature Homeobox Containing Gene (SHOX) Deficiency, SHOX Deficiency-related Disorder
Conditions
Brief summary
GeNeSIS is an open-label, multinational, multicenter, observational study to evaluate the safety and effectiveness of Humatrope treatment. GeNeSIS is a modular program that includes: * Core study: Evaluating the safety and effectiveness of Humatrope in the observational setting * Genetic Analysis Sub-study: Investigating the genetic defects underlying growth hormone (GH) deficiency and non-GH-deficient growth disorders * Growth Prediction Sub-study: Working to validate and refine specific models to accurately predict growth response to GH * Short Stature Homeobox containing gene (SHOX) Deficiency Sub-study: Elucidating the clinical, endocrine and radiological features of participants with SHOX deficiency due to loss of, or mutation in the SHOX gene (including participants with Turner syndrome) * Neoplasia Sub-study: To characterize the natural history of neoplastic disease, especially in relation to recurrence/progression of primary neoplasia or development of secondary neoplasia in children with a history of neoplasia
Interventions
DRUGSomatropin (recombinant deoxyribonucleic acid [rDNA] origin)
Dose, frequency and duration at discretion of attending physician.
Sponsors
Eli Lilly and Company
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Days to No maximum
Healthy volunteers
No
Inclusion criteria
All participants participating in GeNeSIS must be enrolled in the core study. Participants for whom written consent to release information is provided may enter the core study if they meet any of the following inclusion guidelines: * Treatment with Humatrope for improvement of growth. * No treatment with somatropin in participants with a history of neoplasia or in those with any SHOX deficiency-related disorder.
Exclusion criteria
* Participants with closed epiphyses are not eligible for GeNeSIS entry. However, participants may remain in the study if epiphyseal closure occurs during study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Type 2 Diabetes Mellitus in GH-treated Participants | Year 15 | — |
| Primary Malignancies in Participant Without Previous Cancer History | Year 15 | Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated. |
| Final Height (FH) Gain by Diagnostic Group | Baseline through Year 15 | The standard deviation score (SDS) reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Recurrent Neoplasms and Second Neoplasms in Childhood Cancer Survivors | Baseline through Year 15 | Percentage of participants with recurrence/progression of primary neoplastic disease and/or development of secondary neoplasms in childhood cancer survivors. |
| Percentage of Participants With Defects in Genes Associated With Pituitary Development | Baseline through Year 15 | Percentage of participants with genetic defects associated with pituitary development. Genes included but were not limited to GH1, Growth hormone releasing hormone receptor (GHRHR), Homeobox gene expressed in embryonic stem cells (HESX1), LIM homeobox 3 (LHX3), POU domain, class 1, transcription factor 1 (POU1F1), and Prophet of Pit1 (PROP1). |
| Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | Baseline through Year 15 | — |
| Percentage of Participants With De Novo Neoplasms | Baseline through Year 15 | Percentage of participants with the development of de novo neoplastic disease with no history of prior neoplasia. |
| Predicted First Year Height Gain Versus Actual First Year Height Gain | Baseline through Year 15 | The value for predicted and observed is of limited bearing, it is how each participant's predicted versus observed height gain compare and this is best estimated by the R-squared. An estimation parameter would not be a correct format for the R2 data. R2 can take value between 0 and 1 with values closer to 0 representing a poor fit while values closer to 1 representing a perfect fit |
| Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency | Baseline, Year 15 | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treated Treatment with Humatrope for improvement of growth. | 22,311 |
| Untreated No treatment with Humatrope in participants with a history of neoplasia or in those with any SHOX deficiency-related disorder. | 457 |
| Unknown Treatment with Humatrope unknown. | 77 |
| Total | 22,845 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 38 | 0 | 0 |
| Overall Study | Death | 42 | 6 | 0 |
| Overall Study | Lost to Follow-up | 3,052 | 130 | 11 |
| Overall Study | Other Reason per Case Report Form | 2,089 | 103 | 9 |
| Overall Study | Participant Moved | 601 | 21 | 2 |
| Overall Study | Physician Decision | 1,041 | 8 | 4 |
| Overall Study | Received Another GH Product | 79 | 0 | 0 |
| Overall Study | Sponsor Decision | 4,467 | 79 | 23 |
| Overall Study | Study Summary Not Completed | 4,360 | 64 | 22 |
| Overall Study | Third Party Required to Change Brand | 487 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1,761 | 25 | 1 |
Baseline characteristics
| Characteristic | Untreated | Total | Treated | Unknown |
|---|---|---|---|---|
| Age, Customized <=18 years | 427 participants | 22178 participants | 21724 participants | 27 participants |
| Age, Customized >=65 years | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized Between 18 and 65 years | 20 participants | 472 participants | 451 participants | 1 participants |
| Diagnostic Groups All Other Diagnostic Groups Not Listed | 96 participants | 1327 participants | 1226 participants | 5 participants |
| Diagnostic Groups Born Small for Gestational Age (SGA) | 18 participants | 1295 participants | 1276 participants | 1 participants |
| Diagnostic Groups Chronic Renal Insufficiency (CRI) | 0 participants | 87 participants | 87 participants | 0 participants |
| Diagnostic Groups Growth Hormone Deficiency (GHD | 102 participants | 14173 participants | 14049 participants | 22 participants |
| Diagnostic Groups Idiopathic Short Stature (ISS) | 27 participants | 2876 participants | 2844 participants | 5 participants |
| Diagnostic Groups SHOX Deficiency (SHOX-D) | 126 participants | 705 participants | 576 participants | 3 participants |
| Diagnostic Groups Turner Syndrome (TS) | 42 participants | 1913 participants | 1870 participants | 1 participants |
| Diagnostic Groups Unknown | 46 participants | 469 participants | 383 participants | 40 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 977 Participants | 959 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 166 Participants | 9445 Participants | 9279 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 273 Participants | 12423 Participants | 12073 Participants | 77 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 9 Participants | 9 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 263 Participants | 260 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 303 Participants | 295 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 16 Participants | 16 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 298 Participants | 13778 Participants | 13403 Participants | 77 Participants |
| Race (NIH/OMB) White | 148 Participants | 8476 Participants | 8328 Participants | 0 Participants |
| Region of Enrollment Australia | 0 Participants | 87 Participants | 87 Participants | 0 Participants |
| Region of Enrollment Austria | 0 Participants | 103 Participants | 103 Participants | 0 Participants |
| Region of Enrollment Belgium | 0 Participants | 83 Participants | 83 Participants | 0 Participants |
| Region of Enrollment Canada | 17 Participants | 870 Participants | 850 Participants | 3 Participants |
| Region of Enrollment Czechia | 12 Participants | 344 Participants | 332 Participants | 0 Participants |
| Region of Enrollment Denmark | 0 Participants | 6 Participants | 5 Participants | 1 Participants |
| Region of Enrollment Finland | 0 Participants | 28 Participants | 28 Participants | 0 Participants |
| Region of Enrollment France | 150 Participants | 1821 Participants | 1667 Participants | 4 Participants |
| Region of Enrollment Germany | 24 Participants | 2723 Participants | 2685 Participants | 14 Participants |
| Region of Enrollment Greece | 14 Participants | 305 Participants | 290 Participants | 1 Participants |
| Region of Enrollment Hungary | 2 Participants | 334 Participants | 332 Participants | 0 Participants |
| Region of Enrollment Iceland | 0 Participants | 48 Participants | 48 Participants | 0 Participants |
| Region of Enrollment India | 30 Participants | 242 Participants | 212 Participants | 0 Participants |
| Region of Enrollment Italy | 13 Participants | 788 Participants | 771 Participants | 4 Participants |
| Region of Enrollment Japan | 0 Participants | 2356 Participants | 2352 Participants | 4 Participants |
| Region of Enrollment Kazakhstan | 0 Participants | 29 Participants | 29 Participants | 0 Participants |
| Region of Enrollment Lithuania | 0 Participants | 90 Participants | 90 Participants | 0 Participants |
| Region of Enrollment Netherlands | 0 Participants | 320 Participants | 317 Participants | 3 Participants |
| Region of Enrollment Norway | 0 Participants | 8 Participants | 8 Participants | 0 Participants |
| Region of Enrollment Pakistan | 6 Participants | 178 Participants | 172 Participants | 0 Participants |
| Region of Enrollment Russia | 15 Participants | 195 Participants | 180 Participants | 0 Participants |
| Region of Enrollment Singapore | 3 Participants | 16 Participants | 13 Participants | 0 Participants |
| Region of Enrollment Slovakia | 0 Participants | 94 Participants | 94 Participants | 0 Participants |
| Region of Enrollment South Africa | 1 Participants | 109 Participants | 106 Participants | 2 Participants |
| Region of Enrollment Spain | 9 Participants | 1422 Participants | 1404 Participants | 9 Participants |
| Region of Enrollment Sweden | 0 Participants | 53 Participants | 53 Participants | 0 Participants |
| Region of Enrollment Taiwan | 0 Participants | 115 Participants | 114 Participants | 1 Participants |
| Region of Enrollment Thailand | 0 Participants | 33 Participants | 33 Participants | 0 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 42 Participants | 41 Participants | 0 Participants |
| Region of Enrollment United States | 160 Participants | 10003 Participants | 9812 Participants | 31 Participants |
| Sex/Gender, Customized Female | 247 participants | 9175 participants | 8917 participants | 11 participants |
| Sex/Gender, Customized Male | 209 participants | 13588 participants | 13362 participants | 17 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6,180 / 21,177 | 126 / 306 | 0 / 40 |
| serious Total, serious adverse events | 547 / 21,177 | 14 / 306 | 0 / 40 |
Outcome results
Primary
Final Height (FH) Gain by Diagnostic Group
The standard deviation score (SDS) reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated.
Time frame: Baseline through Year 15
Population: All treated participants who reached final height (at least 1: closed epiphyses, height velocity \<2 centimeters per year, or last bone age \>14 years \[girls\] or \>16 years \[boys\]) with baseline height SDS and final height available. Data was not provided for untreated and unknown treatment groups, and could not be calculated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treated | Final Height (FH) Gain by Diagnostic Group | All Baseline Height | -2.42 standard deviation score | Standard Deviation 1.01 |
| Treated | Final Height (FH) Gain by Diagnostic Group | All Final Height | -1.18 standard deviation score | Standard Deviation 1.12 |
| Treated | Final Height (FH) Gain by Diagnostic Group | All Final Height Gain | 1.24 standard deviation score | Standard Deviation 1.08 |
| Treated | Final Height (FH) Gain by Diagnostic Group | GHD Baseline Height | -2.35 standard deviation score | Standard Deviation 1.04 |
| Treated | Final Height (FH) Gain by Diagnostic Group | GHD Final Height | -0.96 standard deviation score | Standard Deviation 1.12 |
| Treated | Final Height (FH) Gain by Diagnostic Group | GHD Final Height Gain | 1.39 standard deviation score | Standard Deviation 1.14 |
| Treated | Final Height (FH) Gain by Diagnostic Group | TS Baseline Height | -2.65 standard deviation score | Standard Deviation 0.089 |
| Treated | Final Height (FH) Gain by Diagnostic Group | TS Final Height | -1.70 standard deviation score | Standard Deviation 0.94 |
| Treated | Final Height (FH) Gain by Diagnostic Group | TS Final Height Gain | 0.95 standard deviation score | Standard Deviation 0.82 |
| Treated | Final Height (FH) Gain by Diagnostic Group | ISS Baseline Height | -2.37 standard deviation score | Standard Deviation 0.8 |
| Treated | Final Height (FH) Gain by Diagnostic Group | ISS Final Height | -1.26 standard deviation score | Standard Deviation 0.96 |
| Treated | Final Height (FH) Gain by Diagnostic Group | ISS Final Height Gain | 1.10 standard deviation score | Standard Deviation 0.98 |
| Treated | Final Height (FH) Gain by Diagnostic Group | SHOX-D Baseline Height | -2.36 standard deviation score | Standard Deviation 0.79 |
| Treated | Final Height (FH) Gain by Diagnostic Group | SHOX-D Final Height | -1.50 standard deviation score | Standard Deviation 0.97 |
| Treated | Final Height (FH) Gain by Diagnostic Group | SHOX-D Final Height Gain | 0.86 standard deviation score | Standard Deviation 0.91 |
| Treated | Final Height (FH) Gain by Diagnostic Group | SGA Baseline Height | -2.57 standard deviation score | Standard Deviation 0.86 |
| Treated | Final Height (FH) Gain by Diagnostic Group | SGA Final Height | -1.47 standard deviation score | Standard Deviation 0.84 |
| Treated | Final Height (FH) Gain by Diagnostic Group | SGA Final Height Gain | 1.11 standard deviation score | Standard Deviation 0.96 |
| Treated | Final Height (FH) Gain by Diagnostic Group | CRI Baseline Height | -2.54 standard deviation score | Standard Deviation 0.9 |
| Treated | Final Height (FH) Gain by Diagnostic Group | CRI Final Height | -1.66 standard deviation score | Standard Deviation 1.27 |
| Treated | Final Height (FH) Gain by Diagnostic Group | CRI Final Height Gain | 0.88 standard deviation score | Standard Deviation 0.81 |
| Treated | Final Height (FH) Gain by Diagnostic Group | Other Baseline Height | -2.70 standard deviation score | Standard Deviation 1.32 |
| Treated | Final Height (FH) Gain by Diagnostic Group | Other Final Height | -1.69 standard deviation score | Standard Deviation 1.33 |
| Treated | Final Height (FH) Gain by Diagnostic Group | Other Final Height Gain | 1.01 standard deviation score | Standard Deviation 1.1 |
| Treated | Final Height (FH) Gain by Diagnostic Group | Unknown Baseline Height | -2.30 standard deviation score | Standard Deviation 1.02 |
| Treated | Final Height (FH) Gain by Diagnostic Group | Unknown Final Height | -1.54 standard deviation score | Standard Deviation 1.1 |
| Treated | Final Height (FH) Gain by Diagnostic Group | Unknown Final Height Gain | 0.75 standard deviation score | Standard Deviation 0.83 |
Primary
Primary Malignancies in Participant Without Previous Cancer History
Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated.
Time frame: Year 15
Population: All treated participants with available age, gender, and at least one follow-up excluding participants with previous cancer cases. Due to the small number of participants involved, untreated and unknown treatment groups, data was not provided and could not be calculated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treated | Primary Malignancies in Participant Without Previous Cancer History | 14 Incident Cases |
Comparison: Epidemiological comparison between incidence of primary malignancies in study versus general population registry data, stratified by age and gender.95% CI: [0.39, 1.2]
Primary
Type 2 Diabetes Mellitus in GH-treated Participants
Time frame: Year 15
Population: All treated participants with available age and calculable follow-up time. The treated participants were not compared with untreated but with rates from general population registries. The untreated participants predominantly contained neoplasm or SHOX deficient diagnoses, therefore had significant baseline differences from treated participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treated | Type 2 Diabetes Mellitus in GH-treated Participants | Ages 0 to 9 | 1 Incident Cases |
| Treated | Type 2 Diabetes Mellitus in GH-treated Participants | Ages 10 to 14 | 9 Incident Cases |
| Treated | Type 2 Diabetes Mellitus in GH-treated Participants | Ages 15 to 19 | 8 Incident Cases |
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.95% CI: [2.24, 5.96]
Secondary
Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency
Time frame: Baseline, Year 15
Population: All SHOX-D Participants, GH-treated, with available height SDS at baseline and final height. Data was not provided for untreated and unknown treatment groups, and could not be calculated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treated | Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency | Height SDS | 0.8 standard deviation score | Standard Deviation 0.9 |
| Treated | Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency | Sitting Height (SH) SDS | 1.4 standard deviation score | Standard Deviation 1 |
| Treated | Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency | Arm Span (AS) SDS | -0.6 standard deviation score | Standard Deviation 6.2 |
| Treated | Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency | SH SDS/Height SDS | -0.7 standard deviation score | Standard Deviation 1.8 |
| Treated | Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency | AS SDS/Height SDS | 1.0 standard deviation score | Standard Deviation 3 |
| Treated | Change From Baseline to Final Height in Anthropometric Measures for Participants With SHOX Deficiency | AS SDS/SH SDS | 10.2 standard deviation score | Standard Deviation 22.9 |
Secondary
Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses
Time frame: Baseline through Year 15
Population: All treated participants with available age and calculable follow-up time, and diabetes mellitus (DM), type 1 diabetes mellitus (T1) or type 2 diabetes mellitus (T2). Data was not provided for untreated and unknown treatment groups, and could not be calculated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | All DM | 38 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | GHD DM | 22 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | TS DM | 6 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | ISS DM | 4 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | SHOX-D DM | 0 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | SGA DM | 2 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | Other DM | 4 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | Unknown DM | 0 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | All T1 | 19 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | GHD T1 | 10 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | TS T1 | 3 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | ISS T1 | 3 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | SHOX-D T1 | 0 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | SGA T1 | 0 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | Other T1 | 3 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | Unknown T1 | 0 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | All T2 | 18 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | GHD T2 | 12 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | TS T2 | 3 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | ISS T2 | 0 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | SHOX-D T2 | 0 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | SGA T2 | 2 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | Other T2 | 1 Incident Cases |
| Treated | Diabetes Mellitus (DM) in Somatropin-Treated Children With Different Short Stature Diagnoses | Unknown T2 | 0 Incident Cases |
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for All DM (T1, T2 and DM Not Otherwise Specified \[NOS\] Combined)95% CI: [2.14, 4.15]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for GHD DM (T1, T2 and DM NOS Combined)95% CI: [1.72, 4.15]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for TS DM (T1, T2 and DM NOS Combined)95% CI: [1.8, 10.69]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for ISS DM (T1, T2 and DM NOS Combined)95% CI: [0.84, 7.93]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for SHOX-D DM (T1, T2 and DM NOS Combined)95% CI: [0, 11.83]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for SGA DM (T1, T2 and DM NOS Combined)95% CI: [0.36, 10.83]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for Other DM (T1, T2 and DM NOS Combined)95% CI: [1.24, 11.66]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for Unknown DM (T1, T2 and DM NOS Combined)95% CI: [0, 24.3]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for All T1 DM.95% CI: [0.56, 1.44]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for GHD T1DM.95% CI: [0.36, 1.4]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for TS T1DM.95% CI: [0.31, 4.38]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for ISS T1DM.95% CI: [0.29, 4.14]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for SHOX-D T1DM.95% CI: [0, 7.23]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for SGA T1DM.95% CI: [0, 3.38]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for Other T1DM.95% CI: [0.43, 6.1]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for Unknown T1DM.95% CI: [0, 14.84]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for All T2 DM.95% CI: [2.24, 5.96]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for GHD T2DM.95% CI: [2.03, 6.87]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for TS T2DM.95% CI: [1.33, 18.89]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for ISS T2DM.95% CI: [0, 7.52]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for SHOX-D T2DM.95% CI: [0, 31.16]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for SGA T2DM.95% CI: [0.96, 28.52]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for Other T2DM.95% CI: [0.08, 16.7]
Comparison: Epidemiological comparison between incidence of type 2 diabetes in study versus general population registry data, stratified by age and ethnicity.~Standardized Incidence Ratio for Unknown T2DM.95% CI: [0, 63.97]
Secondary
Percentage of Participants With Defects in Genes Associated With Pituitary Development
Percentage of participants with genetic defects associated with pituitary development. Genes included but were not limited to GH1, Growth hormone releasing hormone receptor (GHRHR), Homeobox gene expressed in embryonic stem cells (HESX1), LIM homeobox 3 (LHX3), POU domain, class 1, transcription factor 1 (POU1F1), and Prophet of Pit1 (PROP1).
Time frame: Baseline through Year 15
Population: All SME participants (including treated, untreated, and unknown groups) with available results of DNA (deoxyribonucleic acid) analysis available and GHD diagnosis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treated | Percentage of Participants With Defects in Genes Associated With Pituitary Development | 6.7 percentage of participants |
| Untreated | Percentage of Participants With Defects in Genes Associated With Pituitary Development | 14.8 percentage of participants |
| Unknown | Percentage of Participants With Defects in Genes Associated With Pituitary Development | 0.0 percentage of participants |
Secondary
Percentage of Participants With De Novo Neoplasms
Percentage of participants with the development of de novo neoplastic disease with no history of prior neoplasia.
Time frame: Baseline through Year 15
Population: All SME, GH-treated participants with at least one follow-up visit. Data was not provided for untreated and unknown treatment groups, and could not be calculated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treated | Percentage of Participants With De Novo Neoplasms | 0.07 percentage of participants |
Secondary
Percentage of Participants With Recurrent Neoplasms and Second Neoplasms in Childhood Cancer Survivors
Percentage of participants with recurrence/progression of primary neoplastic disease and/or development of secondary neoplasms in childhood cancer survivors.
Time frame: Baseline through Year 15
Population: All SME, treated participants with previous neoplastic disease and at least one follow-up visit. Data was not provided for untreated and unknown treatment groups, and could not be calculated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treated | Percentage of Participants With Recurrent Neoplasms and Second Neoplasms in Childhood Cancer Survivors | Recurrences | 6.81 percentage of participants |
| Treated | Percentage of Participants With Recurrent Neoplasms and Second Neoplasms in Childhood Cancer Survivors | Second Neoplasms | 4.98 percentage of participants |
Secondary
Predicted First Year Height Gain Versus Actual First Year Height Gain
The value for predicted and observed is of limited bearing, it is how each participant's predicted versus observed height gain compare and this is best estimated by the R-squared. An estimation parameter would not be a correct format for the R2 data. R2 can take value between 0 and 1 with values closer to 0 representing a poor fit while values closer to 1 representing a perfect fit
Time frame: Baseline through Year 15
Population: All participants with predicted and actual first year height gain available and TS or GHD diagnosis. Data was not provided for untreated and unknown treatment groups, and could not be calculated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treated | Predicted First Year Height Gain Versus Actual First Year Height Gain | TS | 0.261 R Squared |
| Treated | Predicted First Year Height Gain Versus Actual First Year Height Gain | GHD | 0.408 R Squared |