Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Georgia State University College of Law, Atlanta, Georgia, USA.
Pharmacoepidemiol Drug Saf. 2024 Oct;33(10):e70009. doi: 10.1002/pds.70009.
Research and regulatory approval for pediatric uses of prescription drugs often lag years after adult approvals, during which time substantial off-label use of medications in children can occur. We evaluated whether US Food and Drug Administration (FDA) regulatory actions affected the pediatric use of omalizumab, a biologic drug used to treat asthma.
In this serial cross-sectional study, we identified quarterly cohorts of children (0-18 years) with moderate-to-severe asthma within two large national claims databases of those with commercial insurance and Medicaid from 2003 to 2019. Using an interrupted time-series analysis, we fit segmented linear regression models to identify changes in the incidence of omalizumab use in 6-11-year-old children compared with 12-18-year-olds after two time points: (1) 2009Q3 when an FDA advisory committee voted against use for 6-11-year-old children and (2) 2016Q2 when FDA expanded omalizumab's labeling to include 6-11-year-old children.
We identified 9298 new pediatric omalizumab users (84% Medicaid). Among 6-11-year-old children, the incidence of omalizumab use did not change following the FDA's initial review of evidence in 2009 and increased after 2016 Q2 FDA approval for this age group in both Medicaid (58 per 100 000 children with asthma, 95% confidence interval [CI] 27-89, p < 0.001) and commercial insurance (57 per 100 000, 95% CI 21-94, p = 0.003) compared with 12-18-year-old children.
The use of omalizumab among asthmatic children aged 6-11 years remained steady after FDA advisory committee concerns in 2009 and increased after FDA expanded the indication to include this population in 2016. Additional market incentives may help to ensure the timely generation of evidence and regulatory approval of medications for children.
研究和监管机构对处方药物儿科用途的批准通常滞后于成人批准数年，在此期间，儿童大量使用未经批准的药物的情况时有发生。我们评估了美国食品和药物管理局（FDA）的监管行动是否影响了奥马珠单抗的儿科用途，奥马珠单抗是一种用于治疗哮喘的生物药物。
在这项连续的横断面研究中，我们在两个大型商业保险和医疗补助国家索赔数据库中，确定了 2003 年至 2019 年期间患有中度至重度哮喘的 0-18 岁儿童的季度队列。使用中断时间序列分析，我们拟合分段线性回归模型，以确定在两个时间点后，6-11 岁儿童奥马珠单抗使用率与 12-18 岁儿童相比的变化：（1）2009 年第三季度，FDA 顾问委员会投票反对 6-11 岁儿童使用奥马珠单抗，（2）2016 年第二季度，FDA 将奥马珠单抗的标签扩大到包括 6-11 岁儿童。
我们确定了 9298 名新的儿科奥马珠单抗使用者（84%为医疗补助）。在 6-11 岁儿童中，在 2009 年 FDA 首次审查证据后，奥马珠单抗的使用并未发生变化，并且在 2016 年第二季度 FDA 批准该年龄组使用后增加，在医疗补助（每 10 万哮喘儿童 58 例，95%置信区间[CI] 27-89，p<0.001）和商业保险（每 10 万 57 例，95%CI 21-94，p=0.003）中，6-11 岁儿童的使用量均高于 12-18 岁儿童。
在 2009 年 FDA 顾问委员会提出担忧后，奥马珠单抗在患有哮喘的 6-11 岁儿童中的使用保持稳定，并且在 2016 年 FDA 将适应症扩大到包括该人群后增加。更多的市场激励措施可能有助于确保及时生成证据并监管批准儿童用药。
