ON ESTIMATING EFFICACY FROM CLINICAL-TRIALS
ON ESTIMATING EFFICACY FROM CLINICAL-TRIALS
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DOI：
10.1002/sim.4780100110
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发表时间：
1991-01-01
影响因子：
2
通讯作者：
ZEGER, SL
中科院分区：
文献类型：
--
作者：
SOMMER, A;ZEGER, SL
我们将“生物功效”定义为所有接受指定治疗剂的人的治疗效果。它衡量治疗在依从者中的生物作用。在一种治疗和一种安慰剂对照的随机试验中，理论上可以通过比较完成治疗方案的人和同样完成对照方案的对照组来估计疗效。然而，在实践中，我们进行这种比较是有保留的，因为控制协议对依从性的挑战通常与治疗方案不同，因此依从性的子组是不可比较的。标准做法采用治疗意向比较，将随机分组的患者与对照组患者进行比较，而不考虑他们是否实际接受了治疗。意向治疗比较估计的是治疗的“规划有效性”，而不是其生物学有效性。本文介绍并推导了一种替代性生物功效估计器的统计特性，该估计器避免了在比较依从性亚群时固有的潜在选择偏差。该方法适用于随机试验，无论是否给予对照组安慰剂，结果都是两分法。这个想法是将治疗组的编纂者与推断的控制亚组进行比较，以消除选择偏差。该方法是由一项关于补充维生素a对儿童死亡率影响的随机社区试验的分析所激发的，并在该试验中得到说明。
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.