Optimising the design of phase II oncology trials

The importance of randomisation

Mark J. Ratain, Daniel J. Sargent

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Oncology trial end-points continue to receive considerable attention, as illustrated by the development and revisions to the RECIST criteria. In this article, we focus the reader away from the issue of end-points for phase II trials and towards what we believe to be an even more important issue, the fundamental need for randomisation in phase II oncology trials, ideally with blinding and dose-ranging. We present arguments to support the proposition that randomisation will enable greater clarity in the interpretation of the phase II trial results, as well as allowing for more precise estimates of the effect size and sample size requirements for definitive phase III trials. Randomisation will also reduce potential bias resulting from inter-trial variability, which inflates both type I and II errors if historical controls are utilised. In the context of a randomised blinded trial, the exact choice of end-point is less critical, although we favour end-points such as the change in tumour size or progression status at a fixed early time point (i.e. 8-12 weeks after randomisation). Although end-points based on RECIST criteria can and should be utilised in randomised phase II trials, we do not believe that revision of the RECIST criteria will result in a fundamental improvement in drug development decisions in the absence of randomised clinical trials at the phase II stage of drug development.

Original languageEnglish (US)
Pages (from-to)275-280
Number of pages6
JournalEuropean Journal of Cancer
Volume45
Issue number2
DOIs
StatePublished - Jan 2009

Fingerprint

Random Allocation
Pharmaceutical Preparations
Sample Size
Randomized Controlled Trials
Response Evaluation Criteria in Solid Tumors
Neoplasms

Keywords

  • Clinical trial design
  • Phase II
  • Randomization

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Optimising the design of phase II oncology trials : The importance of randomisation. / Ratain, Mark J.; Sargent, Daniel J.

In: European Journal of Cancer, Vol. 45, No. 2, 01.2009, p. 275-280.

Research output: Contribution to journalArticle

Ratain, Mark J. ; Sargent, Daniel J. / Optimising the design of phase II oncology trials : The importance of randomisation. In: European Journal of Cancer. 2009 ; Vol. 45, No. 2. pp. 275-280.
@article{6c0aa4d7cefe479c8fd17f36202155d0,
title = "Optimising the design of phase II oncology trials: The importance of randomisation",
abstract = "Oncology trial end-points continue to receive considerable attention, as illustrated by the development and revisions to the RECIST criteria. In this article, we focus the reader away from the issue of end-points for phase II trials and towards what we believe to be an even more important issue, the fundamental need for randomisation in phase II oncology trials, ideally with blinding and dose-ranging. We present arguments to support the proposition that randomisation will enable greater clarity in the interpretation of the phase II trial results, as well as allowing for more precise estimates of the effect size and sample size requirements for definitive phase III trials. Randomisation will also reduce potential bias resulting from inter-trial variability, which inflates both type I and II errors if historical controls are utilised. In the context of a randomised blinded trial, the exact choice of end-point is less critical, although we favour end-points such as the change in tumour size or progression status at a fixed early time point (i.e. 8-12 weeks after randomisation). Although end-points based on RECIST criteria can and should be utilised in randomised phase II trials, we do not believe that revision of the RECIST criteria will result in a fundamental improvement in drug development decisions in the absence of randomised clinical trials at the phase II stage of drug development.",
keywords = "Clinical trial design, Phase II, Randomization",
author = "Ratain, {Mark J.} and Sargent, {Daniel J.}",
year = "2009",
month = "1",
doi = "10.1016/j.ejca.2008.10.029",
language = "English (US)",
volume = "45",
pages = "275--280",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
number = "2",

}

TY - JOUR

T1 - Optimising the design of phase II oncology trials

T2 - The importance of randomisation

AU - Ratain, Mark J.

AU - Sargent, Daniel J.

PY - 2009/1

Y1 - 2009/1

N2 - Oncology trial end-points continue to receive considerable attention, as illustrated by the development and revisions to the RECIST criteria. In this article, we focus the reader away from the issue of end-points for phase II trials and towards what we believe to be an even more important issue, the fundamental need for randomisation in phase II oncology trials, ideally with blinding and dose-ranging. We present arguments to support the proposition that randomisation will enable greater clarity in the interpretation of the phase II trial results, as well as allowing for more precise estimates of the effect size and sample size requirements for definitive phase III trials. Randomisation will also reduce potential bias resulting from inter-trial variability, which inflates both type I and II errors if historical controls are utilised. In the context of a randomised blinded trial, the exact choice of end-point is less critical, although we favour end-points such as the change in tumour size or progression status at a fixed early time point (i.e. 8-12 weeks after randomisation). Although end-points based on RECIST criteria can and should be utilised in randomised phase II trials, we do not believe that revision of the RECIST criteria will result in a fundamental improvement in drug development decisions in the absence of randomised clinical trials at the phase II stage of drug development.

AB - Oncology trial end-points continue to receive considerable attention, as illustrated by the development and revisions to the RECIST criteria. In this article, we focus the reader away from the issue of end-points for phase II trials and towards what we believe to be an even more important issue, the fundamental need for randomisation in phase II oncology trials, ideally with blinding and dose-ranging. We present arguments to support the proposition that randomisation will enable greater clarity in the interpretation of the phase II trial results, as well as allowing for more precise estimates of the effect size and sample size requirements for definitive phase III trials. Randomisation will also reduce potential bias resulting from inter-trial variability, which inflates both type I and II errors if historical controls are utilised. In the context of a randomised blinded trial, the exact choice of end-point is less critical, although we favour end-points such as the change in tumour size or progression status at a fixed early time point (i.e. 8-12 weeks after randomisation). Although end-points based on RECIST criteria can and should be utilised in randomised phase II trials, we do not believe that revision of the RECIST criteria will result in a fundamental improvement in drug development decisions in the absence of randomised clinical trials at the phase II stage of drug development.

KW - Clinical trial design

KW - Phase II

KW - Randomization

UR - http://www.scopus.com/inward/record.url?scp=57849154374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57849154374&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2008.10.029

DO - 10.1016/j.ejca.2008.10.029

M3 - Article

VL - 45

SP - 275

EP - 280

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 2

ER -