Cargando…

Statistical inference for extended or shortened phase II studies based on Simon’s two-stage designs

BACKGROUND: Simon’s two-stage designs are popular choices for conducting phase II clinical trials, especially in the oncology trials to reduce the number of patients placed on ineffective experimental therapies. Recently Koyama and Chen (2008) discussed how to conduct proper inference for such studi...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Junjun, Yu, Menggang, Feng, Xi-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4535394/
https://www.ncbi.nlm.nih.gov/pubmed/26048655
http://dx.doi.org/10.1186/s12874-015-0039-5
_version_ 1782385600467304448
author Zhao, Junjun
Yu, Menggang
Feng, Xi-Ping
author_facet Zhao, Junjun
Yu, Menggang
Feng, Xi-Ping
author_sort Zhao, Junjun
collection PubMed
description BACKGROUND: Simon’s two-stage designs are popular choices for conducting phase II clinical trials, especially in the oncology trials to reduce the number of patients placed on ineffective experimental therapies. Recently Koyama and Chen (2008) discussed how to conduct proper inference for such studies because they found that inference procedures used with Simon’s designs almost always ignore the actual sampling plan used. In particular, they proposed an inference method for studies when the actual second stage sample sizes differ from planned ones. METHODS: We consider an alternative inference method based on likelihood ratio. In particular, we order permissible sample paths under Simon’s two-stage designs using their corresponding conditional likelihood. In this way, we can calculate p-values using the common definition: the probability of obtaining a test statistic value at least as extreme as that observed under the null hypothesis. RESULTS: In addition to providing inference for a couple of scenarios where Koyama and Chen’s method can be difficult to apply, the resulting estimate based on our method appears to have certain advantage in terms of inference properties in many numerical simulations. It generally led to smaller biases and narrower confidence intervals while maintaining similar coverages. We also illustrated the two methods in a real data setting. CONCLUSIONS: Inference procedures used with Simon’s designs almost always ignore the actual sampling plan. Reported P-values, point estimates and confidence intervals for the response rate are not usually adjusted for the design’s adaptiveness. Proper statistical inference procedures should be used.
format Online
Article
Text
id pubmed-4535394
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-45353942015-08-14 Statistical inference for extended or shortened phase II studies based on Simon’s two-stage designs Zhao, Junjun Yu, Menggang Feng, Xi-Ping BMC Med Res Methodol Research Article BACKGROUND: Simon’s two-stage designs are popular choices for conducting phase II clinical trials, especially in the oncology trials to reduce the number of patients placed on ineffective experimental therapies. Recently Koyama and Chen (2008) discussed how to conduct proper inference for such studies because they found that inference procedures used with Simon’s designs almost always ignore the actual sampling plan used. In particular, they proposed an inference method for studies when the actual second stage sample sizes differ from planned ones. METHODS: We consider an alternative inference method based on likelihood ratio. In particular, we order permissible sample paths under Simon’s two-stage designs using their corresponding conditional likelihood. In this way, we can calculate p-values using the common definition: the probability of obtaining a test statistic value at least as extreme as that observed under the null hypothesis. RESULTS: In addition to providing inference for a couple of scenarios where Koyama and Chen’s method can be difficult to apply, the resulting estimate based on our method appears to have certain advantage in terms of inference properties in many numerical simulations. It generally led to smaller biases and narrower confidence intervals while maintaining similar coverages. We also illustrated the two methods in a real data setting. CONCLUSIONS: Inference procedures used with Simon’s designs almost always ignore the actual sampling plan. Reported P-values, point estimates and confidence intervals for the response rate are not usually adjusted for the design’s adaptiveness. Proper statistical inference procedures should be used. BioMed Central 2015-06-07 /pmc/articles/PMC4535394/ /pubmed/26048655 http://dx.doi.org/10.1186/s12874-015-0039-5 Text en © Zhao et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhao, Junjun
Yu, Menggang
Feng, Xi-Ping
Statistical inference for extended or shortened phase II studies based on Simon’s two-stage designs
title Statistical inference for extended or shortened phase II studies based on Simon’s two-stage designs
title_full Statistical inference for extended or shortened phase II studies based on Simon’s two-stage designs
title_fullStr Statistical inference for extended or shortened phase II studies based on Simon’s two-stage designs
title_full_unstemmed Statistical inference for extended or shortened phase II studies based on Simon’s two-stage designs
title_short Statistical inference for extended or shortened phase II studies based on Simon’s two-stage designs
title_sort statistical inference for extended or shortened phase ii studies based on simon’s two-stage designs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4535394/
https://www.ncbi.nlm.nih.gov/pubmed/26048655
http://dx.doi.org/10.1186/s12874-015-0039-5
work_keys_str_mv AT zhaojunjun statisticalinferenceforextendedorshortenedphaseiistudiesbasedonsimonstwostagedesigns
AT yumenggang statisticalinferenceforextendedorshortenedphaseiistudiesbasedonsimonstwostagedesigns
AT fengxiping statisticalinferenceforextendedorshortenedphaseiistudiesbasedonsimonstwostagedesigns