Sensitivity analysis of causal inference in a clinical trial subject to crossover

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In many clinical trials it is possible for some subjects to cross over between treatment arms. One can evaluate the effect of crossover by modeling it as a missing-data problem, where for subjects who cross over, one treats the unobserved value of the outcome in the original randomization arm as the missing data. The as-treated analysis is invalid if the crossover is nonignorable, in the sense that the crossovers represent a nonrandom sample of the randomized subjects [1,2]. A recent area of general interest is the development of methods for measuring the sensitivity of inferences to nonignorability in the missing-data mechanism; one such approach is that of Troxel et al. [3]. In this paper we apply their method to the problem of measuring sensitivity to nonignorable crossover in randomized trials, extending it to the case where the crossover mechanism may differ between arms. Our method allows us to identify circumstances under which the as-treated analysis may be more or less sensitive to nonignorable crossover. We illustrate it with the example of a randomized clinical trial (RCT) in multiple sclerosis and a study of the effect of military service on income.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
JournalClinical Trials
Volume1
Issue number1
DOIs
StatePublished - Jan 1 2004

Fingerprint

Clinical Trials
Random Allocation
Multiple Sclerosis
Randomized Controlled Trials

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology

Cite this

Sensitivity analysis of causal inference in a clinical trial subject to crossover. / Xie, Hui; Heitjan, Daniel F.

In: Clinical Trials, Vol. 1, No. 1, 01.01.2004, p. 21-30.

Research output: Contribution to journalArticle

@article{8b186e10d75a4a1396e2635daeea19f2,
title = "Sensitivity analysis of causal inference in a clinical trial subject to crossover",
abstract = "In many clinical trials it is possible for some subjects to cross over between treatment arms. One can evaluate the effect of crossover by modeling it as a missing-data problem, where for subjects who cross over, one treats the unobserved value of the outcome in the original randomization arm as the missing data. The as-treated analysis is invalid if the crossover is nonignorable, in the sense that the crossovers represent a nonrandom sample of the randomized subjects [1,2]. A recent area of general interest is the development of methods for measuring the sensitivity of inferences to nonignorability in the missing-data mechanism; one such approach is that of Troxel et al. [3]. In this paper we apply their method to the problem of measuring sensitivity to nonignorable crossover in randomized trials, extending it to the case where the crossover mechanism may differ between arms. Our method allows us to identify circumstances under which the as-treated analysis may be more or less sensitive to nonignorable crossover. We illustrate it with the example of a randomized clinical trial (RCT) in multiple sclerosis and a study of the effect of military service on income.",
author = "Hui Xie and Heitjan, {Daniel F.}",
year = "2004",
month = "1",
day = "1",
doi = "10.1191/1740774504cn005oa",
language = "English (US)",
volume = "1",
pages = "21--30",
journal = "Clinical Trials",
issn = "1740-7745",
publisher = "SAGE Publications Ltd",
number = "1",

}

TY - JOUR

T1 - Sensitivity analysis of causal inference in a clinical trial subject to crossover

AU - Xie, Hui

AU - Heitjan, Daniel F.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - In many clinical trials it is possible for some subjects to cross over between treatment arms. One can evaluate the effect of crossover by modeling it as a missing-data problem, where for subjects who cross over, one treats the unobserved value of the outcome in the original randomization arm as the missing data. The as-treated analysis is invalid if the crossover is nonignorable, in the sense that the crossovers represent a nonrandom sample of the randomized subjects [1,2]. A recent area of general interest is the development of methods for measuring the sensitivity of inferences to nonignorability in the missing-data mechanism; one such approach is that of Troxel et al. [3]. In this paper we apply their method to the problem of measuring sensitivity to nonignorable crossover in randomized trials, extending it to the case where the crossover mechanism may differ between arms. Our method allows us to identify circumstances under which the as-treated analysis may be more or less sensitive to nonignorable crossover. We illustrate it with the example of a randomized clinical trial (RCT) in multiple sclerosis and a study of the effect of military service on income.

AB - In many clinical trials it is possible for some subjects to cross over between treatment arms. One can evaluate the effect of crossover by modeling it as a missing-data problem, where for subjects who cross over, one treats the unobserved value of the outcome in the original randomization arm as the missing data. The as-treated analysis is invalid if the crossover is nonignorable, in the sense that the crossovers represent a nonrandom sample of the randomized subjects [1,2]. A recent area of general interest is the development of methods for measuring the sensitivity of inferences to nonignorability in the missing-data mechanism; one such approach is that of Troxel et al. [3]. In this paper we apply their method to the problem of measuring sensitivity to nonignorable crossover in randomized trials, extending it to the case where the crossover mechanism may differ between arms. Our method allows us to identify circumstances under which the as-treated analysis may be more or less sensitive to nonignorable crossover. We illustrate it with the example of a randomized clinical trial (RCT) in multiple sclerosis and a study of the effect of military service on income.

UR - http://www.scopus.com/inward/record.url?scp=33644694384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644694384&partnerID=8YFLogxK

U2 - 10.1191/1740774504cn005oa

DO - 10.1191/1740774504cn005oa

M3 - Article

C2 - 16281459

AN - SCOPUS:33644694384

VL - 1

SP - 21

EP - 30

JO - Clinical Trials

JF - Clinical Trials

SN - 1740-7745

IS - 1

ER -