Imperiale T F, Horwitz R I
Department of Medicine, Yale University School of Medicine, New Haven, CT.
Biomed Pharmacother. 1989;43(3):187-96. doi: 10.1016/0753-3322(89)90214-x.
A new controversy has emerged over the results of a case-control study alleging a causal relationship between certain non-steroidal anti-inflammatory agents (NSAIAs) and the risks of agranulocytosis and aplastic anemia. After describing the methods and results of the International Agranulocytosis and Aplastic Anemia (IAAA) study, we review the distinctive methodologic challenges of this study and the requirements for avoiding bias, and then reconcile the study results with the principles of case-control design. As a result of our analysis, we believe that the IAAA study's most important and reliable finding is its documentation of the infrequent occurrences of aplastic anemia and agranulocytosis with analgesic use. In contrast, a causal association between NSAIAs and blood dyscrasias has not been suitably established, and may well have resulted from several distinctive sources of bias. These include the effects of diagnostic-suspicion bias in case determination, of exclusion bias in choosing controls, of recall bias in determining exposure, and of publicity bias in both case selection and ascertainment of exposure. These problems could have been avoided and a more valid result obtained with closer attention to the experimental paradigm for case-control research.
一项病例对照研究的结果引发了新的争议，该研究声称某些非甾体抗炎药（NSAIA）与粒细胞缺乏症和再生障碍性贫血风险之间存在因果关系。在描述了国际粒细胞缺乏症和再生障碍性贫血（IAAA）研究的方法和结果之后，我们回顾了该研究独特的方法学挑战以及避免偏差的要求，然后将研究结果与病例对照设计的原则进行协调。经过分析，我们认为IAAA研究最重要且可靠的发现是其记录了使用镇痛药后再生障碍性贫血和粒细胞缺乏症的罕见发生情况。相比之下，NSAIA与血液系统疾病之间的因果关联尚未得到充分确立，很可能是由几种独特的偏差来源导致的。这些偏差包括病例确定中的诊断怀疑偏差、选择对照时的排除偏差、确定暴露情况时的回忆偏差以及病例选择和暴露确定中的宣传偏差。如果更密切地关注病例对照研究的实验范式，这些问题本可以避免，并能获得更有效的结果。
