Disproportionality analysis of sex-stratified adverse event signals in growth impairment: Insights from the FDA adverse event reporting system.
Somatropin shows a stronger association with growth impairment in females than in males, highlighting the importance of sex-disaggregated pharmacovigilance in pediatric therapies.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study examined sex-disaggregated adverse event signals associated with growth impairment in pediatric patients, focusing on growth hormone and related agents. A disproportionality analysis was performed on 3281 reports from the FDA adverse event reporting system from 2004 Q1 to 2025 Q1. Significant disparities in safety signals were identified, particularly for somatropin, which showed a stronger association with growth impairment in females than in males.
Abstract
This study aimed to examine sex-disaggregated adverse event signals associated with growth impairment in pediatric patients, utilizing data from the FDA adverse event reporting system, with a particular focus on growth hormone and related therapeutic agents. A disproportionality analysis was performed on FDA adverse event reporting system data spanning 2004 Q1 to 2025 Q1. The analysis encompassed 3281 growth impairment-related reports, disaggregated by gender, employing Reporting Odds Ratios (ROR) and proportional reporting ratios for signal detection, with temporal patterns assessed via Weibull distribution modeling. Significant sex-disaggregated disparities in safety signals were identified. Somatropin exhibited a stronger association with growth impairment in females (ROR 76.85, 95% CI 65.52-90.15) than in males (ROR 37.31, 95% CI 32.99-42.20). Deflazacort showed a male-exclusive signal (ROR 58.25, 95% CI 41.27-82.21), while imatinib displayed a higher risk in females (ROR 15.55, 95% CI 11.29-21.42) compared to males (ROR 4.17, 95% CI 2.91-5.99). Temporal analysis revealed an early-failure pattern, with 50.6% of events occurring within 180 days. These findings generate the hypothesis that sex-disaggregated pharmacovigilance in pediatrics, particularly for growth-modulating therapies, may reveal differential reporting patterns. Should these signals be validated in controlled prospective studies, they could inform the development of customized monitoring frameworks and dosing strategies aimed at potentially mitigating risks in hypothesized high-risk subgroups.
Background
This paper addresses the safety signals associated with growth impairment in pediatric patients, particularly focusing on the effects of growth hormone therapies. Previous studies have indicated potential adverse effects of these therapies, but sex-disaggregated data have been limited. Understanding these signals is crucial for improving pharmacovigilance and patient safety in pediatric populations.
Methods
A disproportionality analysis was conducted using data from the FDA adverse event reporting system, covering reports from Q1 2004 to Q1 2025. The analysis included 3281 reports related to growth impairment, disaggregated by gender. Reporting Odds Ratios (ROR) and proportional reporting ratios were utilized for signal detection, with temporal patterns assessed using Weibull distribution modeling.
Results
The primary finding was that somatropin exhibited a stronger association with growth impairment in females (ROR 76.85, 95% CI 65.52-90.15) compared to males (ROR 37.31, 95% CI 32.99-42.20). Deflazacort showed a male-exclusive signal (ROR 58.25, 95% CI 41.27-82.21), while imatinib presented a higher risk in females (ROR 15.55, 95% CI 11.29-21.42) than in males (ROR 4.17, 95% CI 2.91-5.99). Additionally, 50.6% of adverse events occurred within 180 days.
Interpretation
These findings suggest significant sex-disaggregated differences in adverse event reporting for growth impairment associated with somatropin and other therapies. While the reported ROR values indicate statistical significance, the clinical relevance of these findings requires further investigation. The study's reliance on adverse event reports introduces potential confounding factors, including underreporting and bias, which may limit the conclusions drawn.
Key findings
- ROR 76.85, 95% CI 65.52-90.15 for females using somatropin.
- ROR 37.31, 95% CI 32.99-42.20 for males using somatropin.
- ROR 58.25, 95% CI 41.27-82.21 for deflazacort in males.
- ROR 15.55, 95% CI 11.29-21.42 for imatinib in females.
- ROR 4.17, 95% CI 2.91-5.99 for imatinib in males.
- 50.6% of events occurred within 180 days.
Limitations
- Observational study based on adverse event reporting data.
- Potential underreporting and bias in adverse event data.
- Findings require validation in controlled prospective studies.
- Single-source data may not represent broader population trends.