The choice of test in phase II cancer trials assessing continuous tumour shrinkage when complete responses are expected

Traditionally, phase II cancer trials test a binary endpoint formed from a dichotomisation of the continuous change in tumour size. Directly testing the continuous endpoint provides considerable gains in power, although also results in several statistical issues. One such issue is when complete resp...

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Main Authors:	Wason, James MS, Mander, Adrian P
Format:	Online
Language:	English
Published:	SAGE Publications 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668774/

id	pubmed-4668774
recordtype	oai_dc
spelling	pubmed-46687742015-12-10 The choice of test in phase II cancer trials assessing continuous tumour shrinkage when complete responses are expected Wason, James MS Mander, Adrian P Articles Traditionally, phase II cancer trials test a binary endpoint formed from a dichotomisation of the continuous change in tumour size. Directly testing the continuous endpoint provides considerable gains in power, although also results in several statistical issues. One such issue is when complete responses, i.e. complete tumour removal, are observed in multiple patients; this is a problem when normality is assumed. Using simulated data and a recently published phase II trial, we investigate how the choice of test affects the operating characteristics of the trial. We propose using parametric tests based on the censored normal distribution, comparing them to the t-test and Wilcoxon non-parametric test. The censored normal distribution fits the real dataset well, but simulations indicate its type-I error rate is inflated, and its power is only slightly higher than the t-test. The Wilcoxon test has deflated type I error. For two-arm designs, the differences are much smaller. We conclude that the t-test is suitable for use when complete responses are present, although positively skewed data can result in the non-parametric test having higher power. SAGE Publications 2015-12 /pmc/articles/PMC4668774/ /pubmed/22179821 http://dx.doi.org/10.1177/0962280211432192 Text en © The Author(s) 2011 http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page(https://us.sagepub.com/en-us/nam/open-access-at-sage).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wason, James MS Mander, Adrian P
spellingShingle	Wason, James MS Mander, Adrian P The choice of test in phase II cancer trials assessing continuous tumour shrinkage when complete responses are expected
author_facet	Wason, James MS Mander, Adrian P
author_sort	Wason, James MS
title	The choice of test in phase II cancer trials assessing continuous tumour shrinkage when complete responses are expected
title_short	The choice of test in phase II cancer trials assessing continuous tumour shrinkage when complete responses are expected
title_full	The choice of test in phase II cancer trials assessing continuous tumour shrinkage when complete responses are expected
title_fullStr	The choice of test in phase II cancer trials assessing continuous tumour shrinkage when complete responses are expected
title_full_unstemmed	The choice of test in phase II cancer trials assessing continuous tumour shrinkage when complete responses are expected
title_sort	choice of test in phase ii cancer trials assessing continuous tumour shrinkage when complete responses are expected
description	Traditionally, phase II cancer trials test a binary endpoint formed from a dichotomisation of the continuous change in tumour size. Directly testing the continuous endpoint provides considerable gains in power, although also results in several statistical issues. One such issue is when complete responses, i.e. complete tumour removal, are observed in multiple patients; this is a problem when normality is assumed. Using simulated data and a recently published phase II trial, we investigate how the choice of test affects the operating characteristics of the trial. We propose using parametric tests based on the censored normal distribution, comparing them to the t-test and Wilcoxon non-parametric test. The censored normal distribution fits the real dataset well, but simulations indicate its type-I error rate is inflated, and its power is only slightly higher than the t-test. The Wilcoxon test has deflated type I error. For two-arm designs, the differences are much smaller. We conclude that the t-test is suitable for use when complete responses are present, although positively skewed data can result in the non-parametric test having higher power.
publisher	SAGE Publications
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668774/
_version_	1613509258012262400

The choice of test in phase II cancer trials assessing continuous tumour shrinkage when complete responses are expected

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