Background Biannual azithromycin distribution to children 1–59 months old reduced all-cause mortality by 18% [incidence rate ratio (IRR) 0.82, 95% confidence interval (CI): 0.74, 0.90] in an intention-to-treat analysis of a randomized controlled trial in Niger. Estimation of the effect in compliance-related subgroups can support decision making around implementation of this intervention in programmatic settings. Methods The cluster-randomized, placebo-controlled design of the original trial enabled unbiased estimation of the effect of azithromycin on mortality rates in two subgroups: (i) treated children (complier average causal effect analysis); and (ii) untreated children (spillover effect analysis), using negative binomial regression. Results In Niger, 594 eligible communities were randomized to biannual azithromycin or placebo distribution and were followed from December 2014 to August 2017, with a mean treatment coverage of 90% [standard deviation (SD) 10%] in both arms. Subgroup analyses included 2581 deaths among treated children and 245 deaths among untreated children. Among treated children, the incidence rate ratio comparing mortality in azithromycin communities to placebo communities was 0.80 (95% CI: 0.72, 0.88), with mortality rates (deaths per 1000 person-years at risk) of 16.6 in azithromycin communities and 20.9 in placebo communities. Among untreated children, the incidence rate ratio was 0.91 (95% CI: 0.69, 1.21), with rates of 33.6 in azithromycin communities and 34.4 in placebo communities. Conclusions As expected, this analysis suggested similar efficacy among treated children compared with the intention-to-treat analysis. Though the results were consistent with a small spillover benefit to untreated children, this trial was underpowered to detect spillovers.

中文翻译：

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尼日尔依从性相关亚组的阿奇霉素分布和儿童死亡率：整群随机、安慰剂对照试验中的依从者平均因果效应和溢出效应

背景 一项对 1-59 个月大儿童的半年一次阿奇霉素分发使全因死亡率降低了 18% [发生率比 (IRR) 0.82，95% 置信区间 (CI)：0.74，0.90]在尼日尔进行的随机对照试验。对依从性相关亚组的影响的估计可以支持围绕在规划环境中实施该干预措施的决策。方法 原始试验的整群随机、安慰剂对照设计能够无偏估计阿奇霉素对两个亚组死亡率的影响：(ii) 未经治疗的儿童（溢出效应分析），使用负二项式回归。结果在尼日尔，594 个符合条件的社区被随机分配到一年两次的阿奇霉素或安慰剂分配组，并在 2014 年 12 月至 2017 年 8 月期间进行了随访，两组的平均治疗覆盖率为 90% [标准差 (SD) 10%]。亚组分析包括 2581 例治疗儿童死亡和 245 例未治疗儿童死亡。在接受治疗的儿童中，阿奇霉素社区与安慰剂社区死亡率的发生率比为 0.80（95% CI：0.72，0.88），阿奇霉素社区的死亡率（每 1000 人年风险死亡数）为 16.6，安慰剂组为 20.9社区。在未经治疗的儿童中，发病率比为 0.91（95% CI：0.69，1.21），阿奇霉素组为 33.6，安慰剂组为 34.4。结论正如预期的那样，该分析表明，与意向治疗分析相比，接受治疗的儿童的疗效相似。尽管结果与未治疗儿童的小溢出效应一致，但该试验不足以检测溢出效应。