Revealing and addressing length bias and heterogeneous effects in frequency case-crossover studies.
Revealing and addressing length bias and heterogeneous effects in frequency case-crossover studies.
复制标题
揭示和解决频率案例交叉研究中的长度偏差和异质效应。
DOI：
10.1093/aje/kwh078
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发表时间：
2004
影响因子：
5
通讯作者：
Frangakis,ConstantineE
中科院分区：
文献类型：
--
作者：
Varadhan,Ravi;Frangakis,ConstantineE
病例交叉设计可用于评估复发性暴露（例如，药物）触发事件（例如，心肌梗死），仅使用病例，当找到良好的对照是不切实际的。在基本频率设计中，将事件发生前一段时间内观察到的病例暴露几率与基于其过去暴露的通常频率的预期暴露几率进行比较。这相当于在无暴露-事件关系的零假设下，将观察到的事件与末次暴露之间的间隔时间与基于受试者暴露经验的预期间隔时间进行比较。这样的比较揭示了常频分析中的两个问题：1）即使在零假设下也存在长度偏差; 2）当暴露效应确实存在时，效率损失。第一个问题的出现是因为即使在零假设下，事件发生的时间也很可能比平均时间长，从而导致风险比率的系统性向下偏差。第二个问题是由于将病例分类为接触或未接触，以及没有充分利用事件与先前接触之间的间隔时间数据。提出了一种新的分析方法，它不受长度偏差的影响，并有效地利用了间隙时间数据。
The case-crossover design is useful for assessing whether a recurrent exposure (e.g., drug) triggers an event (e.g., myocardial infarction), using only cases, when finding good controls is impractical. In the basic frequency design, the observed exposure odds among cases, during a period immediately before the event, are compared with the expected exposure odds, based on their usual frequency of past exposures. This is equivalent to comparing observed gap times between the event and the last exposure with the expected gap times based on the subjects’ exposure experience under the null hypothesis of no exposure-event relation. Such a comparison reveals two problems in the usual-frequency analyses: 1) length bias that exists even under the null hypothesis; and 2) loss of efficiency when exposure effects do exist. The first problem arises because the event will more likely fall on a longer-than-average period between exposures, even under the null hypothesis, resulting in a systematic downward bias of risk ratios. The second problem arises from categorizing cases as exposed or unexposed and from not fully using the data on gap times between events and preceding exposures. A new method of analysis is presented that is free from length bias and that efficiently uses gap time data.