A likelihood-based, counterfactual approach to accounting for treatment failures in clinical trials

Michele L. Shaffer, Vernon Chinchilli

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Consider a two-armed, placebo-controlled trial in which subjects may experience treatment failure. For ethical reasons, it is necessary to administer emergency or rescue medications for such subjects. However, the emergency medications may bias the set of response measurements. When analyzing the data from clinical trials, the standard approach is to perform an intent-to-treat (ITT) analysis, wherein the data are analyzed according to treatment assignment. Secondary statistical analyses that supplement the ITT analysis can be performed to account for the impact of treatment failures and emergency medications. A likelihood-based, counterfactual approach to supplemental analyses uses the expectation maximization (EM) algorithm for parameter estimation and a likelihood ratio test to test the equality of the placebo and experimental treatment means for subjects who would not fail under either treatment assignment. A simulation study is performed to assess the operating characteristics of the likelihood ratio test. An example from the Asthma Clinical Research Network (ACRN) is used to draw comparisons between the standard ITT procedure and the developed supplemental analysis.

Original languageEnglish (US)
Pages (from-to)481-494
Number of pages14
JournalJournal of Biopharmaceutical Statistics
Volume13
Issue number3
DOIs
StatePublished - Aug 15 2003

Fingerprint

Treatment Failure
Clinical Trials
Likelihood
Emergencies
Emergency
Placebos
Likelihood Ratio Test
Assignment
Therapeutics
Asthma
Operating Characteristics
Expectation-maximization Algorithm
Parameter Estimation
Equality
Research
Simulation Study
Necessary
Standards

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

@article{1f05affc3db04b90b11bb5dd7a3fb4e9,
title = "A likelihood-based, counterfactual approach to accounting for treatment failures in clinical trials",
abstract = "Consider a two-armed, placebo-controlled trial in which subjects may experience treatment failure. For ethical reasons, it is necessary to administer emergency or rescue medications for such subjects. However, the emergency medications may bias the set of response measurements. When analyzing the data from clinical trials, the standard approach is to perform an intent-to-treat (ITT) analysis, wherein the data are analyzed according to treatment assignment. Secondary statistical analyses that supplement the ITT analysis can be performed to account for the impact of treatment failures and emergency medications. A likelihood-based, counterfactual approach to supplemental analyses uses the expectation maximization (EM) algorithm for parameter estimation and a likelihood ratio test to test the equality of the placebo and experimental treatment means for subjects who would not fail under either treatment assignment. A simulation study is performed to assess the operating characteristics of the likelihood ratio test. An example from the Asthma Clinical Research Network (ACRN) is used to draw comparisons between the standard ITT procedure and the developed supplemental analysis.",
author = "Shaffer, {Michele L.} and Vernon Chinchilli",
year = "2003",
month = "8",
day = "15",
doi = "10.1081/BIP-120022768",
language = "English (US)",
volume = "13",
pages = "481--494",
journal = "Journal of Biopharmaceutical Statistics",
issn = "1054-3406",
publisher = "Taylor and Francis Ltd.",
number = "3",

}

A likelihood-based, counterfactual approach to accounting for treatment failures in clinical trials. / Shaffer, Michele L.; Chinchilli, Vernon.

In: Journal of Biopharmaceutical Statistics, Vol. 13, No. 3, 15.08.2003, p. 481-494.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A likelihood-based, counterfactual approach to accounting for treatment failures in clinical trials

AU - Shaffer, Michele L.

AU - Chinchilli, Vernon

PY - 2003/8/15

Y1 - 2003/8/15

N2 - Consider a two-armed, placebo-controlled trial in which subjects may experience treatment failure. For ethical reasons, it is necessary to administer emergency or rescue medications for such subjects. However, the emergency medications may bias the set of response measurements. When analyzing the data from clinical trials, the standard approach is to perform an intent-to-treat (ITT) analysis, wherein the data are analyzed according to treatment assignment. Secondary statistical analyses that supplement the ITT analysis can be performed to account for the impact of treatment failures and emergency medications. A likelihood-based, counterfactual approach to supplemental analyses uses the expectation maximization (EM) algorithm for parameter estimation and a likelihood ratio test to test the equality of the placebo and experimental treatment means for subjects who would not fail under either treatment assignment. A simulation study is performed to assess the operating characteristics of the likelihood ratio test. An example from the Asthma Clinical Research Network (ACRN) is used to draw comparisons between the standard ITT procedure and the developed supplemental analysis.

AB - Consider a two-armed, placebo-controlled trial in which subjects may experience treatment failure. For ethical reasons, it is necessary to administer emergency or rescue medications for such subjects. However, the emergency medications may bias the set of response measurements. When analyzing the data from clinical trials, the standard approach is to perform an intent-to-treat (ITT) analysis, wherein the data are analyzed according to treatment assignment. Secondary statistical analyses that supplement the ITT analysis can be performed to account for the impact of treatment failures and emergency medications. A likelihood-based, counterfactual approach to supplemental analyses uses the expectation maximization (EM) algorithm for parameter estimation and a likelihood ratio test to test the equality of the placebo and experimental treatment means for subjects who would not fail under either treatment assignment. A simulation study is performed to assess the operating characteristics of the likelihood ratio test. An example from the Asthma Clinical Research Network (ACRN) is used to draw comparisons between the standard ITT procedure and the developed supplemental analysis.

UR - http://www.scopus.com/inward/record.url?scp=0041633644&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041633644&partnerID=8YFLogxK

U2 - 10.1081/BIP-120022768

DO - 10.1081/BIP-120022768

M3 - Article

VL - 13

SP - 481

EP - 494

JO - Journal of Biopharmaceutical Statistics

JF - Journal of Biopharmaceutical Statistics

SN - 1054-3406

IS - 3

ER -