Efficacy of phototherapy for newborns with hyperbilirubinemia: a cautionary example of an instrumental variable analysis.
Efficacy of phototherapy for newborns with hyperbilirubinemia: a cautionary example of an instrumental variable analysis.
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DOI：
10.1177/0272989x11416512
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
McCulloch CE
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文献类型：
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作者：
Newman TB;Vittinghoff E;McCulloch CE
在治疗的观察性研究中，使用工具变量作为控制适应症混淆的方法越来越受欢迎。以新生儿黄疸光疗的工具变量分析为例，说明未测量的仪器水平治疗替代如何扭曲效应量估计。回顾性队列研究。北方加州凯撒医疗机构医院。作者研究了20，731名出生于1995-2004年的≥2000 g且妊娠≥35周的新生儿，其“合格”血清总胆红素（TSB）水平在2004年美国儿科学会（AAP）光疗阈值的3 mg/dL范围内，且未进行阳性直接抗球蛋白试验。干预措施是在合格TSB后8小时内进行住院光疗。结果是TSB水平超过AAP换血阈值，距离合格TSB <48小时。工具变量是衡量新生儿出生医院光疗使用频率的指标。未测量的替代治疗是补充婴儿配方奶粉，通过对同一队列样本的图表审查进行评估。共有128名婴儿（0.62%）超过了换血阈值。Logistic和倾向性分析得出光疗疗效的粗比值比为0.5，对照适应症的混杂因素后下降至0.2。仪器变量分析表明，光疗的疗效要大得多（例如，比值比为0.02-0.05）。然而，图表审查显示，在使用更多光疗的医院中，婴儿配方奶粉的使用量更大（这也降低了胆红素水平）（r = 0.56; P = 0.02），但这种关联在个体水平上不存在（r = 0.13）。如果在工具水平上存在与治疗相关的共同干预或混杂因素，即使这些相关性在个体中可能不存在，工具变量分析也可能提供治疗疗效的偏倚估计。
Use of instrumental variables is gaining popularity as a method of controlling for confounding by indication in observational studies of treatments. To illustrate how unmeasured instrument-level treatment substitution can distort effect size estimates using as an example an instrumental variable analysis of phototherapy for neonatal jaundice. Retrospective cohort study. Northern California Kaiser Permanente Hospitals. The authors studied 20,731 newborns ≥2000 g and ≥35 weeks' gestation born 1995–2004 with a “qualifying” total serum bilirubin (TSB) level within 3 mg/dL of the 2004 American Academy of Pediatrics (AAP) phototherapy threshold who did not have a positive direct antiglobulin test. The intervention was inpatient phototherapy within 8 hours of the qualifying TSB. The outcome was a TSB level exceeding the AAP exchange transfusion threshold <48 hours from the qualifying TSB. The instrumental variable was a measure of the frequency of phototherapy use at the newborn's birth hospital. The unmeasured substituted treatment was supplementation with infant formula, assessed by chart review in a sample from the same cohort. In total, 128 infants (0.62%) exceeded the exchange transfusion threshold. Logistic and propensity analyses yielded crude odds ratios of ∼0.5 for phototherapy efficacy, decreasing to ∼0.2 with control for confounding by indication. Instrumental variable analyses suggested much greater phototherapy efficacy (e.g., odds ratios of 0.02–0.05). However, chart reviews revealed greater use of infant formula (which also lowers bilirubin levels) in hospitals that used more phototherapy (r = 0.56; P = 0.02), an association not present at the individual level (r = 0.13). Instrumental variable analyses may provide biased estimates of treatment efficacy if there are cointer-ventions or confounders associated with treatment at the level of the instrument, even when these associations may not exist in individuals.