Marshfield Clinic Research Foundation, Epidemiology Research Center (ML2), 1000 North Oak Ave, Marshfield, WI 54449, USA.
Pediatr Infect Dis J. 2010 Jan;29(1):1-5. doi: 10.1097/INF.0b013e3181af8605.
A pentavalent, bovine-derived rotavirus vaccine (RotaTeq, Merck) was licensed in 2006 for use in infants. A previously licensed rotavirus vaccine was withdrawn due to elevated risk of intussusception. We prospectively evaluated the risk of intussusception and other pre-specified adverse events among RotaTeq recipients in the Vaccine Safety Datalink.
The exposed population included children from age 4 to 48 weeks who received RotaTeq between May 2006 and May 2008. Adverse events over the subsequent 30 days were ascertained from inpatient, outpatient, and emergency department files; cases of intussusception were validated by medical record review. An adaptation of sequential probability ratio testing was employed to compare the cumulative number of observed and expected adverse events on a weekly basis, and a "signal" was generated if the log-likelihood ratio reached a predetermined threshold. This allowed near real-time monitoring to detect selected adverse events. The expected number of cases of intussusception was determined from historical rates in the VSD population.
There were 207,621 doses of RotaTeq administered to the study population; 42% were first doses. Five children had computerized diagnosis codes for intussusception, and 6.75 cases were expected based on historical rates (relative risk = 0.74). No elevation in risk was identified for intussusception or any other adverse event. Two of five children with suspected intussusception based on diagnosis codes met the case criteria after medical record review.
This study illustrates the feasibility of rapid vaccine safety assessment and provides additional evidence that RotaTeq is not associated with an increased risk of intussusception.
一种五价、牛源轮状病毒疫苗（RotaTeq，默克公司）于 2006 年获得许可，用于婴儿。此前获得许可的轮状病毒疫苗因肠套叠风险增加而被撤回。我们前瞻性地评估了疫苗安全数据链中 RotaTeq 接种者肠套叠和其他预定不良事件的风险。
暴露人群包括 4 至 48 周龄的儿童，他们在 2006 年 5 月至 2008 年 5 月期间接受了 RotaTeq 治疗。通过住院、门诊和急诊档案确定了随后 30 天内的不良事件；肠套叠病例通过病历审查进行验证。采用序贯概率比检验的一种变体，每周比较观察到和预期的不良事件的累积数量，如果对数似然比达到预定阈值，则生成“信号”。这允许实时监测以检测选定的不良事件。肠套叠的预期病例数是根据 VSD 人群中的历史发生率确定的。
研究人群中有 207621 剂 RotaTeq 接种；42%为首次剂量。5 名儿童的计算机诊断代码为肠套叠，根据历史数据，预计有 6.75 例（相对风险=0.74）。未发现肠套叠或任何其他不良事件的风险增加。根据诊断代码怀疑患有肠套叠的 5 名儿童中有 2 名经病历审查后符合病例标准。
本研究说明了快速疫苗安全性评估的可行性，并提供了额外的证据表明 RotaTeq 与肠套叠风险增加无关。
