Keyboard: A novel Bayesian toxicity probability interval design for phase I clinical trials

Fangrong Yan, Sumithra J Mandrekar, Ying Yuan

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The primary objective of phase I oncology trials is to find the MTD. The 3 + 3 design is easy to implement but performs poorly in finding the MTD. A newer design, such as the modified toxicity probability interval (mTPI) design, provides better accuracy to identify the MTD but tends to overdose patients. We propose the keyboard design, an intuitive Bayesian design that conducts dose escalation and de-escalation based on whether the strongest key, defined as the dosing interval that most likely contains the current dose, is below or above the target dosing interval. The keyboard design can be implemented in a simple way, similar to the traditional 3 þ 3 design, but provides more flexibility for choosing the target toxicity rate and cohort size. Our simulation studies demonstrate that compared with the 3 + 3 design, the keyboard design has favorable operating characteristics in terms of identifying the MTD. Compared with the mTPI design, the keyboard design is safer, with a substantially lower risk of treating patients at overly toxic doses, and has the better precision to identify the MTD, thereby providing a useful upgrade to the mTPI design. Software freely available at http:// www.trialdesign.org facilitates the application of the keyboard design.

Original languageEnglish (US)
Pages (from-to)3994-4003
Number of pages10
JournalClinical Cancer Research
Volume23
Issue number15
DOIs
StatePublished - Aug 1 2017

Fingerprint

Clinical Trials, Phase I
Poisons
Software

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Keyboard : A novel Bayesian toxicity probability interval design for phase I clinical trials. / Yan, Fangrong; Mandrekar, Sumithra J; Yuan, Ying.

In: Clinical Cancer Research, Vol. 23, No. 15, 01.08.2017, p. 3994-4003.

Research output: Contribution to journalArticle

@article{b94864d6369344fab5f346e124ddcb55,
title = "Keyboard: A novel Bayesian toxicity probability interval design for phase I clinical trials",
abstract = "The primary objective of phase I oncology trials is to find the MTD. The 3 + 3 design is easy to implement but performs poorly in finding the MTD. A newer design, such as the modified toxicity probability interval (mTPI) design, provides better accuracy to identify the MTD but tends to overdose patients. We propose the keyboard design, an intuitive Bayesian design that conducts dose escalation and de-escalation based on whether the strongest key, defined as the dosing interval that most likely contains the current dose, is below or above the target dosing interval. The keyboard design can be implemented in a simple way, similar to the traditional 3 {\th} 3 design, but provides more flexibility for choosing the target toxicity rate and cohort size. Our simulation studies demonstrate that compared with the 3 + 3 design, the keyboard design has favorable operating characteristics in terms of identifying the MTD. Compared with the mTPI design, the keyboard design is safer, with a substantially lower risk of treating patients at overly toxic doses, and has the better precision to identify the MTD, thereby providing a useful upgrade to the mTPI design. Software freely available at http:// www.trialdesign.org facilitates the application of the keyboard design.",
author = "Fangrong Yan and Mandrekar, {Sumithra J} and Ying Yuan",
year = "2017",
month = "8",
day = "1",
doi = "10.1158/1078-0432.CCR-17-0220",
language = "English (US)",
volume = "23",
pages = "3994--4003",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "15",

}

TY - JOUR

T1 - Keyboard

T2 - A novel Bayesian toxicity probability interval design for phase I clinical trials

AU - Yan, Fangrong

AU - Mandrekar, Sumithra J

AU - Yuan, Ying

PY - 2017/8/1

Y1 - 2017/8/1

N2 - The primary objective of phase I oncology trials is to find the MTD. The 3 + 3 design is easy to implement but performs poorly in finding the MTD. A newer design, such as the modified toxicity probability interval (mTPI) design, provides better accuracy to identify the MTD but tends to overdose patients. We propose the keyboard design, an intuitive Bayesian design that conducts dose escalation and de-escalation based on whether the strongest key, defined as the dosing interval that most likely contains the current dose, is below or above the target dosing interval. The keyboard design can be implemented in a simple way, similar to the traditional 3 þ 3 design, but provides more flexibility for choosing the target toxicity rate and cohort size. Our simulation studies demonstrate that compared with the 3 + 3 design, the keyboard design has favorable operating characteristics in terms of identifying the MTD. Compared with the mTPI design, the keyboard design is safer, with a substantially lower risk of treating patients at overly toxic doses, and has the better precision to identify the MTD, thereby providing a useful upgrade to the mTPI design. Software freely available at http:// www.trialdesign.org facilitates the application of the keyboard design.

AB - The primary objective of phase I oncology trials is to find the MTD. The 3 + 3 design is easy to implement but performs poorly in finding the MTD. A newer design, such as the modified toxicity probability interval (mTPI) design, provides better accuracy to identify the MTD but tends to overdose patients. We propose the keyboard design, an intuitive Bayesian design that conducts dose escalation and de-escalation based on whether the strongest key, defined as the dosing interval that most likely contains the current dose, is below or above the target dosing interval. The keyboard design can be implemented in a simple way, similar to the traditional 3 þ 3 design, but provides more flexibility for choosing the target toxicity rate and cohort size. Our simulation studies demonstrate that compared with the 3 + 3 design, the keyboard design has favorable operating characteristics in terms of identifying the MTD. Compared with the mTPI design, the keyboard design is safer, with a substantially lower risk of treating patients at overly toxic doses, and has the better precision to identify the MTD, thereby providing a useful upgrade to the mTPI design. Software freely available at http:// www.trialdesign.org facilitates the application of the keyboard design.

UR - http://www.scopus.com/inward/record.url?scp=85027138844&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027138844&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-17-0220

DO - 10.1158/1078-0432.CCR-17-0220

M3 - Article

C2 - 28546227

AN - SCOPUS:85027138844

VL - 23

SP - 3994

EP - 4003

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 15

ER -