TY - JOUR
T1 - On estimating efficacy from clinical trials
AU - Sommer, Alfred
AU - Zeger, Scott L.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1991/1
Y1 - 1991/1
N2 - 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.
AB - 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.
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U2 - 10.1002/sim.4780100110
DO - 10.1002/sim.4780100110
M3 - Article
C2 - 2006355
AN - SCOPUS:0025968778
SN - 0277-6715
VL - 10
SP - 45
EP - 52
JO - Statistics in Medicine
JF - Statistics in Medicine
IS - 1
ER -