Sommer A, Zeger S L
Department of Ophthalmology, Johns Hopkins University, Baltimore, MD 21205.
Stat Med. 1991 Jan;10(1):45-52. doi: 10.1002/sim.4780100110.
We define 'biologic efficacy' as the effect of treatment for all persons who receive the therapeutic agent to which they were assigned. It measures the biologic action of treatment among compliant persons. In a randomized trial with one treatment and one placebo control, one can theoretically estimate efficacy by comparing persons who complete the treatment regimen with controls who similarly complete the control regimen. In practice, however, we make this comparison with reservation because a control protocol often presents a different challenge for compliance than does the treatment, so that the compliant subgroups are not comparable. Standard practice employs intent-to-treat comparisons in which one compares those randomized to treatment and control without reference to whether they actually received the treatment. Intent-to-treat comparisons estimate the 'programmatic effectiveness' of a treatment rather than its biologic efficacy. This paper introduces and derives the statistical properties of an alternative estimator of biologic efficacy that avoids the potential selection bias inherent in a comparison of compliant subgroups. The method applies to randomized trials with a dichotomous outcome measure, whether or not a placebo is given to the control group. The idea is to compare the compliers in the treatment group to an inferred control subgroup chosen to eliminate selection bias. The methodology was motivated by and is illustrated in the analysis of a randomized community trial of the impact of vitamin A supplementation on children's mortality.
我们将“生物学疗效”定义为接受所分配治疗药物的所有患者的治疗效果。它衡量的是依从性良好的患者中治疗的生物学作用。在一项有一个治疗组和一个安慰剂对照组的随机试验中，理论上可以通过比较完成治疗方案的患者与同样完成对照方案的对照组患者来估计疗效。然而，在实际操作中，我们对此比较有所保留，因为对照方案往往在依从性方面带来与治疗不同的挑战，所以依从性子组不可比。标准做法采用意向性分析比较，即比较随机分配到治疗组和对照组的患者，而不考虑他们是否实际接受了治疗。意向性分析比较估计的是治疗的“方案有效性”而非其生物学疗效。本文介绍并推导了一种生物学疗效替代估计量的统计特性，该估计量避免了依从性子组比较中固有的潜在选择偏倚。该方法适用于具有二分结局指标的随机试验，无论对照组是否给予安慰剂。其思路是将治疗组中的依从者与为消除选择偏倚而选择的推断对照组进行比较。该方法的灵感来源于一项关于维生素A补充剂对儿童死亡率影响的随机社区试验分析，并在该分析中得到了说明。
