Monitoring the rates of composite events with censored data in phase II clinical trials

Y. K. Cheung, P. F. Thall

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

In many phase II clinical trials, interim monitoring is based on the probability of a binary event, response, defined in terms of one or more time-to-event variables within a time period of fixed length. Such outcome-adaptive methods may require repeated interim suspension of accrual in order to follow each patient for the time period required to evaluate response. This may increase trial duration, and eligible patients arriving during such delays either must wait for accrual to reopen or be treated outside the trial. Alternatively, monitoring may be done continuously by ignoring censored data each time the stopping rule is applied, which wastes information. We propose an adaptive Bayesian method that eliminates these problems. At each patient's accrual time, an approximate posterior for the response probability based on all of the event-time data is used to compute an early stopping criterion. Application to a leukemia trial with a composite event shows that the method can reduce trial duration substantially while maintaining the reliability of interim decisions.

Original languageEnglish (US)
Pages (from-to)89-97
Number of pages9
JournalBiometrics
Volume58
Issue number1
DOIs
StatePublished - Jan 1 2002

Fingerprint

Phase II Clinical Trials
Censored Data
Clinical Trials
clinical trials
Composite
Monitoring
monitoring
Composite materials
Adaptive Method
Suspensions
duration
Bayesian theory
leukemia
Early Stopping
Stopping Criterion
Stopping Rule
Leukemia
Bayesian Methods
Bayes Theorem
Period of time

Keywords

  • Approximate posterior
  • Competing risks
  • Dependent censoring
  • Historical data
  • Interim analyses
  • Mixture of beta distributions

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Cite this

Monitoring the rates of composite events with censored data in phase II clinical trials. / Cheung, Y. K.; Thall, P. F.

In: Biometrics, Vol. 58, No. 1, 01.01.2002, p. 89-97.

Research output: Contribution to journalArticle

@article{61ada36a5f5f45eaa4f53d3b1909110a,
title = "Monitoring the rates of composite events with censored data in phase II clinical trials",
abstract = "In many phase II clinical trials, interim monitoring is based on the probability of a binary event, response, defined in terms of one or more time-to-event variables within a time period of fixed length. Such outcome-adaptive methods may require repeated interim suspension of accrual in order to follow each patient for the time period required to evaluate response. This may increase trial duration, and eligible patients arriving during such delays either must wait for accrual to reopen or be treated outside the trial. Alternatively, monitoring may be done continuously by ignoring censored data each time the stopping rule is applied, which wastes information. We propose an adaptive Bayesian method that eliminates these problems. At each patient's accrual time, an approximate posterior for the response probability based on all of the event-time data is used to compute an early stopping criterion. Application to a leukemia trial with a composite event shows that the method can reduce trial duration substantially while maintaining the reliability of interim decisions.",
keywords = "Approximate posterior, Competing risks, Dependent censoring, Historical data, Interim analyses, Mixture of beta distributions",
author = "Cheung, {Y. K.} and Thall, {P. F.}",
year = "2002",
month = "1",
day = "1",
doi = "10.1111/j.0006-341X.2002.00089.x",
language = "English (US)",
volume = "58",
pages = "89--97",
journal = "Biometrics",
issn = "0006-341X",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Monitoring the rates of composite events with censored data in phase II clinical trials

AU - Cheung, Y. K.

AU - Thall, P. F.

PY - 2002/1/1

Y1 - 2002/1/1

N2 - In many phase II clinical trials, interim monitoring is based on the probability of a binary event, response, defined in terms of one or more time-to-event variables within a time period of fixed length. Such outcome-adaptive methods may require repeated interim suspension of accrual in order to follow each patient for the time period required to evaluate response. This may increase trial duration, and eligible patients arriving during such delays either must wait for accrual to reopen or be treated outside the trial. Alternatively, monitoring may be done continuously by ignoring censored data each time the stopping rule is applied, which wastes information. We propose an adaptive Bayesian method that eliminates these problems. At each patient's accrual time, an approximate posterior for the response probability based on all of the event-time data is used to compute an early stopping criterion. Application to a leukemia trial with a composite event shows that the method can reduce trial duration substantially while maintaining the reliability of interim decisions.

AB - In many phase II clinical trials, interim monitoring is based on the probability of a binary event, response, defined in terms of one or more time-to-event variables within a time period of fixed length. Such outcome-adaptive methods may require repeated interim suspension of accrual in order to follow each patient for the time period required to evaluate response. This may increase trial duration, and eligible patients arriving during such delays either must wait for accrual to reopen or be treated outside the trial. Alternatively, monitoring may be done continuously by ignoring censored data each time the stopping rule is applied, which wastes information. We propose an adaptive Bayesian method that eliminates these problems. At each patient's accrual time, an approximate posterior for the response probability based on all of the event-time data is used to compute an early stopping criterion. Application to a leukemia trial with a composite event shows that the method can reduce trial duration substantially while maintaining the reliability of interim decisions.

KW - Approximate posterior

KW - Competing risks

KW - Dependent censoring

KW - Historical data

KW - Interim analyses

KW - Mixture of beta distributions

UR - http://www.scopus.com/inward/record.url?scp=0036186030&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036186030&partnerID=8YFLogxK

U2 - 10.1111/j.0006-341X.2002.00089.x

DO - 10.1111/j.0006-341X.2002.00089.x

M3 - Article

C2 - 11890331

AN - SCOPUS:0036186030

VL - 58

SP - 89

EP - 97

JO - Biometrics

JF - Biometrics

SN - 0006-341X

IS - 1

ER -