International Institute of Health Management Research, New Delhi, India.
Simpson University, Redding, CA, USA.
Int J Risk Saf Med. 2024;35(3):207-215. doi: 10.3233/JRS-230049.
The self-controlled case series (SCCS) is often used to monitor vaccine safety. The evaluation of intussusception after the rotavirus vaccine is complicated because the baseline rate varies with age. Time-varying baseline risk adjustments with data from unexposed cohorts are utilised. Self-controlled risk interval (SCRI), with a shorter observation period, can also mitigate the problem by studying a control period close to the risk period.
An Indian rotavirus vaccine has previously been studied using SCCS. The risk of intussusception in the high-risk windows (21 days after vaccination) was comparable to the background risk. The aim was to re-analyse data of an existing SCCS study using alternate statistical methods to examine vaccine safety.
We examined the mean age of intussusception in the vaccinated and the unvaccinated. We performed an SCRI analysis of the surveillance data from the SCCS study, limiting the observation period to 180 days. We analysed the time-to-intussusception from the last vaccination. Finally, we performed an SCCS analysis, excluding unvaccinated cases from the analysis.
We found that the mean age of intussusception was significantly lower in the vaccinated (205 days) compared to the unvaccinated (223 days) (p-value 0.0026). The Incident Risk Ratio (IRR) on SCRI analysis was 1.62 (95% CI 1.07-2.44). There were significantly more intussusceptions in the first 30 days after vaccination compared to the next 30-day window. (92 vs 63 p-value = 0.009). We found that excluding unvaccinated infants from the SCCS analysis demonstrated significantly increased risk for the risk period 1-21 days after the 3rd dose (IRR 2.47, 95% CI 1.70-3.59). The risks of intussusception were missed in traditional SCCS analysis using unvaccinated infants as controls.
Traditional risk adjustments using data from unexposed cohorts in SCCS may not be appropriate for investigating the risk of intussusception where vaccination lowers the mean age of intussusception.
自身对照病例系列（SCCS）常用于监测疫苗安全性。轮状病毒疫苗接种后监测肠套叠的情况较为复杂，因为基础发病率随年龄而变化。采用无暴露队列的数据进行时变基线风险调整。利用较短的观察期的自身对照风险间隔（SCRI），通过研究接近风险期的对照期也可以减轻这个问题。
之前已经使用 SCCS 对印度轮状病毒疫苗进行了研究。高风险窗口（接种后 21 天）内肠套叠的风险与背景风险相当。目的是使用替代统计方法重新分析现有 SCCS 研究的数据，以检查疫苗安全性。
我们检查了接种组和未接种组肠套叠的平均年龄。我们对 SCCS 研究的监测数据进行了 SCRI 分析，将观察期限制在 180 天内。我们分析了从最后一次接种到发生肠套叠的时间。最后，我们进行了 SCCS 分析，将未接种的病例排除在分析之外。
我们发现，接种组的肠套叠平均年龄明显低于未接种组（205 天比 223 天，p 值=0.0026）。SCRI 分析的发病率比值比（IRR）为 1.62（95%置信区间 1.07-2.44）。与下一个 30 天窗口相比，接种后 30 天内发生肠套叠的数量明显更多（92 例比 63 例，p 值=0.009）。我们发现，将未接种的婴儿从 SCCS 分析中排除后，第 3 剂后 1-21 天的风险期内的风险显著增加（IRR 2.47，95%置信区间 1.70-3.59）。传统的 SCCS 分析使用未接种的婴儿作为对照，可能会忽略肠套叠的风险。
在接种降低肠套叠平均年龄的情况下，SCCS 中使用无暴露队列的数据进行传统的风险调整可能不适合调查肠套叠的风险。
