De´partement de Pharmacologie-Universite´ de Bordeaux, France.
Drug Saf. 2011 Oct 1;34(10):861-8. doi: 10.2165/11592140-000000000-00000.
The case-population approach or population-based case-cohort approach is derived from the case-control design and consists of comparing past exposure to a given risk factor in subjects presenting a given disease or symptom (cases) with the exposure rate to this factor in the whole cohort or in the source population of cases. In the same way as the case-control approach, the case-population approach measures the disproportionality of exposure between cases of a given disease and their source population expressed in the form of an odds ratio approximating the ratio of the risks in exposed and not-exposed populations (relative risk).
The aim of this study was to (i) present the case-population principle design in a way understandable for non-statisticians; (ii) propose the easiest way of using it for pharmacovigilance purposes (mainly alerting and hypothesis testing); (iii) propose simple formulae for computing an odds ratio and its confidence interval; (iv) apply the approach to several practical and published examples; and (v) discuss its pros and cons in the context of real life.
The approach used is derived from that comparing two rates expressed as person-time denominators. It allows easy computation of an odds ratio and its confidence interval under several hypotheses. Results obtained with the case-population approach were compared with those of case-control studies published in the literature.
Relevance and limits of the proposed approach are illustrated by examples taken from published pharmacoepidemiological studies. The odds ratio (OR) reported in a European case-control study on centrally acting appetite suppressants and primary pulmonary hypertension was 23.1 (95% CI 6.9, 77.7) versus 31 (95% CI 16.2, 59.2) using the case-population approach. In the European case-control studies SCAR (Severe Cutaneous Adverse Reactions) and EuroSCAR on the risk of toxic epidermal necrolysis associated with the use of medicines, the OR for cotrimoxazole was 160 and 102, respectively, versus 44.4 using the case-population approach. Similarly, these two case-control studies found ORs of 12 and 72 for carbamazepine versus 24.4 using the case-population approach, 8.7 and 16 for phenobarbital versus 21.9, 12 for piroxicam (analysed in the SCAR study only) versus 14.5, and 5.5 and 18 for allopurinol versus 3.4 using the case-population approach.
Being based on the estimate derived from sales statistics of the total exposure time in the source population of cases, the method can be used even when there is no information about the actual number of exposed subjects in this population. Although the case-population approach suffers from limitations stemming from its main advantage, i.e. impossibility to control possible confounders and to quantify the strength of associations due to the absence of an ad hoc control group, it is particularly useful to use in routine practice, mainly for purposes of signal generation and hypothesis testing in drug surveillance.
病例人群法或基于人群的病例-队列法源自病例对照设计，包括比较在出现特定疾病或症状的人群（病例）中过去对特定风险因素的暴露情况，以及在整个队列或病例来源人群中对该因素的暴露率。与病例对照方法一样，病例人群法通过计算比值比来衡量特定疾病病例与其来源人群之间暴露的不成比例性，该比值比近似于暴露和未暴露人群风险之比（相对风险）。
本研究旨在（i）以非统计学家易于理解的方式介绍病例人群原理设计；（ii）提出一种最简单的方法，用于药物警戒目的（主要是警报和假设检验）；（iii）提出计算比值比及其置信区间的简单公式；（iv）将该方法应用于几个实际的已发表示例；（v）在现实生活背景下讨论其优缺点。
所使用的方法源自比较两个以人时为分母表示的比率。它允许在几种假设下轻松计算比值比及其置信区间。用病例人群法得到的结果与文献中发表的病例对照研究的结果进行了比较。
通过取自已发表药物流行病学研究的示例说明了所提出方法的相关性和局限性。在欧洲一项关于中枢作用食欲抑制剂和原发性肺动脉高压的病例对照研究中，病例人群法报告的比值比（OR）为 23.1（95%置信区间 6.9，77.7），而病例对照研究报告的 OR 为 31（95%置信区间 16.2，59.2）。在欧洲病例对照研究 SCAR（严重皮肤不良反应）和 EuroSCAR 中，与使用药物相关的中毒性表皮坏死松解症风险，甲氧苄啶的 OR 分别为 160 和 102，而病例人群法报告的 OR 为 44.4。同样，这两项病例对照研究中卡马西平的 OR 分别为 12 和 72，病例人群法报告的 OR 为 24.4，苯巴比妥的 OR 为 8.7 和 16，病例人群法报告的 OR 为 21.9，吡罗昔康（仅在 SCAR 研究中分析）的 OR 为 12，病例人群法报告的 OR 为 14.5，别嘌醇的 OR 为 5.5 和 18，病例人群法报告的 OR 为 3.4。
由于基于病例来源人群中总暴露时间的销售统计数据估计，即使在没有该人群中实际暴露人数信息的情况下，也可以使用该方法。虽然病例人群法存在一些局限性，这些局限性源于其主要优势，即不可能控制可能的混杂因素，并且由于缺乏专门的对照组而无法量化关联的强度，但在常规实践中，特别是在药物监测中进行信号生成和假设检验方面，它特别有用。
