Cargando…

Sequential boundaries approach in clinical trials with unequal allocation ratios

BACKGROUND: In clinical trials, both unequal randomization design and sequential analyses have ethical and economic advantages. In the single-stage-design (SSD), however, if the sample size is not adjusted based on unequal randomization, the power of the trial will decrease, whereas with sequential...

Descripción completa

Detalles Bibliográficos
Autores principales: Jafari, Peyman, Ayatollahi, Seyyed Mohammad Taghi, Behboodian, Javad
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1382245/
https://www.ncbi.nlm.nih.gov/pubmed/16412232
http://dx.doi.org/10.1186/1471-2288-6-1
_version_ 1782126853631246336
author Jafari, Peyman
Ayatollahi, Seyyed Mohammad Taghi
Behboodian, Javad
author_facet Jafari, Peyman
Ayatollahi, Seyyed Mohammad Taghi
Behboodian, Javad
author_sort Jafari, Peyman
collection PubMed
description BACKGROUND: In clinical trials, both unequal randomization design and sequential analyses have ethical and economic advantages. In the single-stage-design (SSD), however, if the sample size is not adjusted based on unequal randomization, the power of the trial will decrease, whereas with sequential analysis the power will always remain constant. Our aim was to compare sequential boundaries approach with the SSD when the allocation ratio (R) was not equal. METHODS: We evaluated the influence of R, the ratio of the patients in experimental group to the standard group, on the statistical properties of two-sided tests, including the two-sided single triangular test (TT), double triangular test (DTT) and SSD by multiple simulations. The average sample size numbers (ASNs) and power (1-β) were evaluated for all tests. RESULTS: Our simulation study showed that choosing R = 2 instead of R = 1 increases the sample size of SSD by 12% and the ASN of the TT and DTT by the same proportion. Moreover, when R = 2, compared to the adjusted SSD, using the TT or DTT allows to retrieve the well known reductions of ASN observed when R = 1, compared to SSD. In addition, when R = 2, compared to SSD, using the TT and DTT allows to obtain smaller reductions of ASN than when R = 1, but maintains the power of the test to its planned value. CONCLUSION: This study indicates that when the allocation ratio is not equal among the treatment groups, sequential analysis could indeed serve as a compromise between ethicists, economists and statisticians.
format Text
id pubmed-1382245
institution National Center for Biotechnology Information
language English
publishDate 2006
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-13822452006-02-28 Sequential boundaries approach in clinical trials with unequal allocation ratios Jafari, Peyman Ayatollahi, Seyyed Mohammad Taghi Behboodian, Javad BMC Med Res Methodol Research Article BACKGROUND: In clinical trials, both unequal randomization design and sequential analyses have ethical and economic advantages. In the single-stage-design (SSD), however, if the sample size is not adjusted based on unequal randomization, the power of the trial will decrease, whereas with sequential analysis the power will always remain constant. Our aim was to compare sequential boundaries approach with the SSD when the allocation ratio (R) was not equal. METHODS: We evaluated the influence of R, the ratio of the patients in experimental group to the standard group, on the statistical properties of two-sided tests, including the two-sided single triangular test (TT), double triangular test (DTT) and SSD by multiple simulations. The average sample size numbers (ASNs) and power (1-β) were evaluated for all tests. RESULTS: Our simulation study showed that choosing R = 2 instead of R = 1 increases the sample size of SSD by 12% and the ASN of the TT and DTT by the same proportion. Moreover, when R = 2, compared to the adjusted SSD, using the TT or DTT allows to retrieve the well known reductions of ASN observed when R = 1, compared to SSD. In addition, when R = 2, compared to SSD, using the TT and DTT allows to obtain smaller reductions of ASN than when R = 1, but maintains the power of the test to its planned value. CONCLUSION: This study indicates that when the allocation ratio is not equal among the treatment groups, sequential analysis could indeed serve as a compromise between ethicists, economists and statisticians. BioMed Central 2006-01-13 /pmc/articles/PMC1382245/ /pubmed/16412232 http://dx.doi.org/10.1186/1471-2288-6-1 Text en Copyright © 2006 Jafari et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Jafari, Peyman
Ayatollahi, Seyyed Mohammad Taghi
Behboodian, Javad
Sequential boundaries approach in clinical trials with unequal allocation ratios
title Sequential boundaries approach in clinical trials with unequal allocation ratios
title_full Sequential boundaries approach in clinical trials with unequal allocation ratios
title_fullStr Sequential boundaries approach in clinical trials with unequal allocation ratios
title_full_unstemmed Sequential boundaries approach in clinical trials with unequal allocation ratios
title_short Sequential boundaries approach in clinical trials with unequal allocation ratios
title_sort sequential boundaries approach in clinical trials with unequal allocation ratios
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1382245/
https://www.ncbi.nlm.nih.gov/pubmed/16412232
http://dx.doi.org/10.1186/1471-2288-6-1
work_keys_str_mv AT jafaripeyman sequentialboundariesapproachinclinicaltrialswithunequalallocationratios
AT ayatollahiseyyedmohammadtaghi sequentialboundariesapproachinclinicaltrialswithunequalallocationratios
AT behboodianjavad sequentialboundariesapproachinclinicaltrialswithunequalallocationratios