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Published in: Trials 1/2009

Open Access 01-12-2009 | Methodology

How do multi-stage, multi-arm trials compare to the traditional two-arm parallel group design – a reanalysis of 4 trials

Authors: FM-S Barthel, MKB Parmar, P Royston

Published in: Trials | Issue 1/2009

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Abstract

Background

To speed up the evaluation of new therapies, the multi-arm, multi-stage trial design was suggested previously by the authors.

Methods

In this paper, we evaluate the performance of the two-stage, multi-arm design using four cancer trials conducted at the MRC CTU. The performance of the design at fictitious interim analyses is assessed using a conditional bootstrap approach.

Results

Two main aims are addressed: the error rate of correctly carrying on/stopping the trial at an interim analysis as well as quantifying the gains in terms of resources by employing this design. Furthermore, we make suggestions for the best timing of this interim analysis.

Conclusion

Multi-arm, multi-stage trials are an effective way of speeding up the therapy evaluation process. The design performs well in terms of the type I and II error rates.
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Literature
1.
go back to reference Royston P, Parmar MKB, Qian W: Novel designs for multi-arm clinical trials with survival outcomes, with an application in ovarian cancer. Statistics in Medicine. 2003, 22 (14): 2239-2256. 10.1002/sim.1430.CrossRefPubMed Royston P, Parmar MKB, Qian W: Novel designs for multi-arm clinical trials with survival outcomes, with an application in ovarian cancer. Statistics in Medicine. 2003, 22 (14): 2239-2256. 10.1002/sim.1430.CrossRefPubMed
2.
go back to reference Goldman B, LeBlanc M, Crowley J: Interim futility analysis with intermediate endpoints. Clinical Trials. 2008, 5: 14-22. 10.1177/1740774507086648.CrossRefPubMed Goldman B, LeBlanc M, Crowley J: Interim futility analysis with intermediate endpoints. Clinical Trials. 2008, 5: 14-22. 10.1177/1740774507086648.CrossRefPubMed
3.
go back to reference Lan K, DeMets D: Discrete sequential boundaries for clinical trials. Biometrika. 1983, 70: 659-663. 10.2307/2336502.CrossRef Lan K, DeMets D: Discrete sequential boundaries for clinical trials. Biometrika. 1983, 70: 659-663. 10.2307/2336502.CrossRef
4.
go back to reference Pampallona S, Tsiatis A, Kim KM: Interim monitoring of group sequential trials using spending functions for the type i and ii error probabilities. Drug Information Journal. 2001, 35: 1113-1121.CrossRef Pampallona S, Tsiatis A, Kim KM: Interim monitoring of group sequential trials using spending functions for the type i and ii error probabilities. Drug Information Journal. 2001, 35: 1113-1121.CrossRef
5.
go back to reference Good P: Resampling Methods: a practical guide to data analysis. Birkhaeuser. 2001CrossRef Good P: Resampling Methods: a practical guide to data analysis. Birkhaeuser. 2001CrossRef
6.
go back to reference MRC Renal Cancer Collaborators: Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised trial. Lancet. 1999, 353: 14-17. 10.1016/S0140-6736(98)03544-2.CrossRef MRC Renal Cancer Collaborators: Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised trial. Lancet. 1999, 353: 14-17. 10.1016/S0140-6736(98)03544-2.CrossRef
7.
go back to reference The International Collaborative Ovarian Neoplasm (ICON) Group: Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002, 360: 505-515. 10.1016/S0140-6736(02)09738-6.CrossRef The International Collaborative Ovarian Neoplasm (ICON) Group: Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002, 360: 505-515. 10.1016/S0140-6736(02)09738-6.CrossRef
8.
go back to reference The ICON and AGO Collaborators: Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-2.2trial. Lancet. 2003, 361: 2099-2106. 10.1016/S0140-6736(03)13718-X.CrossRef The ICON and AGO Collaborators: Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-2.2trial. Lancet. 2003, 361: 2099-2106. 10.1016/S0140-6736(03)13718-X.CrossRef
9.
go back to reference Seymour M, Maughan T, Ledermann J, Topham C, James R, Gwyther S, Smith D, Shepherd S, Maraveyas A, Ferry D, Meade A, Thompson L, Griffiths G, Parmar M, Stephens R: Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007, 370: 143-52. 10.1016/S0140-6736(07)61087-3.CrossRefPubMed Seymour M, Maughan T, Ledermann J, Topham C, James R, Gwyther S, Smith D, Shepherd S, Maraveyas A, Ferry D, Meade A, Thompson L, Griffiths G, Parmar M, Stephens R: Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007, 370: 143-52. 10.1016/S0140-6736(07)61087-3.CrossRefPubMed
10.
go back to reference Barthel F, Royston P, Parmar M: A menu-driven facility for sample size calculation in novel multi-arm, multi-stage randomised controlled trials with a survival-time outcome. Stata Journal. 2009, Barthel F, Royston P, Parmar M: A menu-driven facility for sample size calculation in novel multi-arm, multi-stage randomised controlled trials with a survival-time outcome. Stata Journal. 2009,
11.
go back to reference Machin D, Cheung YB, Parmar MKB: Survival Analysis – A Practical Approach. 2006, John Wiley and Sons, England, 2CrossRef Machin D, Cheung YB, Parmar MKB: Survival Analysis – A Practical Approach. 2006, John Wiley and Sons, England, 2CrossRef
12.
go back to reference US Food and Drug Administration: Innovation or stagnation: Challenge and opportunity on the critical path to new medical products. US Dept of Health and Human Services. 2004 US Food and Drug Administration: Innovation or stagnation: Challenge and opportunity on the critical path to new medical products. US Dept of Health and Human Services. 2004
Metadata
Title
How do multi-stage, multi-arm trials compare to the traditional two-arm parallel group design – a reanalysis of 4 trials
Authors
FM-S Barthel
MKB Parmar
P Royston
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Trials / Issue 1/2009
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-10-21

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