The case-crossover study design in pharmacoepidemiology
The case-crossover study design in pharmacoepidemiology
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DOI：
10.1177/0962280208092346
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发表时间：
2009-02-01
影响因子：
2.3
通讯作者：
Suissa, Samy
中科院分区：
文献类型：
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作者：
Delaney, Joseph A. 'Chris';Suissa, Samy
在研究短暂药物暴露与急性结局的关系时，病例交叉设计是病例对照方法的有效替代方法。该设计完全基于病例系列，使用药物暴露随时间变化的受试者内比较来估计与研究药物相关结局的率比。这种设计本质上消除了来自估计速率比的不可测量的、时不变的混杂因素的偏置效应，但对几个假设敏感。我们说明了病例交叉设计，并探讨了其敏感性使用的数据从4028例胃肠道出血的全科医学研究数据库在评估药物华法林的影响。我们比较了使用不同的时间窗长度来评估暴露，并考虑使用病例-时间-对照设计来解释暴露时间趋势。使用1个月的时间窗，病例交叉研究方法未发现华法林暴露有额外的出血风险[率比0.98; 95%置信区间（CI）：0.74-1.28]。当我们将分析限制在真正短暂药物暴露的受试者（定义为前一年的1至3次处方）时，率比为2. 59（95% CI：1. 42 - 4. 74）。为了考虑较长的1年暴露时间窗，使用病例-时间-对照方法，得出率比为1.72（95% CI：1.08-2.43）。结论：病例交叉设计是一种潜在的药物风险评估方法。然而，这种设计对药物使用的不稳定性和暴露时间窗的长度的假设高度敏感，如与华法林使用相关的出血的例子所证明的。
In the study of the association of transient drug exposures with acute outcomes, the case-crossover design is an efficient alternative to the case-control approach. This design based exclusively on the case series uses within-subject comparisons of drug exposures over time to estimate the rate ratio of the outcome associated with the drug under Study. This design inherently removes the biasing effects of unmeasured, time-invariant confounding factors from the estimated rate ratio, but IS Sensitive to several assumptions. We illustrated the case-crossover design and explored its sensitivity using data from 4028 cases of gastrointestinal bleeding from the General Practice Research Database in assessing the effects of the drug warfarin. We compared the use of different time window lengths to assess exposure and considered the use of a case-time-control design to account for exposure time trends. The case-crossovcr approach found no excess risk of bleeding with warfarin exposure [rate ratio 0.98; 95% confidence interval (CI): 0.74-1.28] using a 1-month time window. When we restricted the analysis to Subjects with truly, transient drug exposure, defined by I to 3 prescriptions in the previous year, the rate ratio was 2.59 (95% CI: 1.42-4.74). To consider the longer 1-year exposure time window, the case-time-control approach was used and resulted in a rate ratio of 1.72 (95% CI: 1.08-2.43). In Conclusion, the case-crossover design is potentially a powerful approach to assess the risk of drugs. This design is, however, highly sensitive to assumptions about intermittency of drug use and the length of the exposure time window, as demonstrated with the example of bleeding associated with warfarin use.