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Publisher: Taylor & Francis Inc.
Languages: English
Types: Article
Subjects: QA, R1
In an adaptive seamless phase II/III clinical trial interim\ud analysis data are used for treatment selection, enabling resources to be focussed on comparison of more effective treatment(s) with a control. In this paper we compare two methods recently proposed to enable use of short-term endpoint data for decision-making at the interim analysis. The comparison focusses on the power and the probability of correctly identifying the most promising treatment. We show that the choice of method depends on how well short-term data predict the best treatment, which may be measured by the correlation between treatment effects on short-term and long-term endpoints.
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    • Barnes, P., Pocock, S., Magnussen, H., Iqbal, A., Kramer, B., Higgins, M., Lawrence, D. (2010). Integrating indacaterol dose selection in a clinical study in COPD using an adaptive seamless design. Pulmonary Pharmacology and Therapeutics 23:165-171.
    • Bauer, P., Kieser, M. (1999). Combining different phases in the development of medical treatments within a single trial. Statistics in Medicine 18:1833-1848.
    • Brannath, W., Posch, M., Bauer, P. (2002). Recursive combination tests. Journal of the American Statistical Association 97:236-244.
    • Bretz, F., Koenig, F., Brannath, W., Glimm, E., Posch, M. (2009). Tutorial in biostatistics: Adaptive designs for confirmatory clinical trials. Statistics in Medicine 28:1181-1217.
    • Bretz, F., Schmidli, H., König, F., Racine, A., Maurer, W. (2006). Confirmatory seamless phase II/III clinical trials with hypotheses selection at interim: General concepts. Biometrical Journal 48:623-634.
    • Chataway, J., Nicholas, R., Todd, S., Miller, D., Parsons, N., Valdés-Márquez, E., Stallard, N., Friede, T. (2011). A novel adaptive design strategy increases the efficiency of clinical trials in secondary progressive multiple sclerosis. Multiple Sclerosis 17:81-88.
    • Chow, S.-C., Chang, M., Pong, A. (2005). Statistical consideration of adaptive methods in clinical development. Journal of Biopharmaceutical Statistics 15:575-591.
    • Cook, R., Farewell, V. (1996). Incorporating surrogate endpoints into group sequential trials. Biometrical Journal 38:119-130.
    • Dragalin, V. (2011). An introduction to adaptive designs and adaptation in CNS trials. European Neuropsychopharmacology 21(2):153-158.
    • Dunnett, C. W. (1955). A multiple comparison procedure for comparing several treatments with a control. Journal of the American Statistical Association 50:1096-1121.
    • Engel, B., Walstra, P. (1991). Increasing precision or reducing expense in regression experiments by using information from a concomitant variable. Biometrics 47(1):13-20.
    • European Medicines Agency (EMEA) - Committee for Medicinal Products for Human Use (CHMP) (2007). CHMP reflection paper on methodological issues in confirmatory clinical trials planned with an adaptive design. http://www.emea.europa.eu/docs/en_GB/document_library/ Scientific_guideline/2009/09/WC500003616.pdf (accessed July 13, 2012).
    • Food and Drug Administration (FDA) (2010). Guidance for industry - adaptive design clinical trials for drugs and biologics. http://www.fda.gov/downloads/Drugs/Guidance ComplianceRegulatoryInformation/Guidances/ucm201790.pdf (accessed July 13, 2012).
    • Friede, T., Parsons, N., Stallard, N., Todd, S., Valdés-Márquez, E., Chataway, J., Nicholas, R. (2011). Designing a seamless phase II/III clinical trial using early outcomes for treatment selection: an application in multiple sclerosis. Statistics in Medicine 30:1528-1540.
    • Friede, T., Stallard, N. (2008). A comparison of methods for adaptive treatment selection. Biometrical Journal 50:767-781.
    • Galbraith, S., Marschner, I. (2003). Interim analysis of continuous long-term endpoints in clinical trials with longitudinal outcomes. Statistics in Medicine 22:1787-1805.
    • Gallo, P., Chuang-Stein, C., Dragalin, V., Gaydos, B., Krams, M., Pinheiro, J. (2006). Adaptive designs in clinical drug development - an executive summary of the pharma working group. Journal of Biopharmaceutical Statistics 16:275-283.
    • Genz, A., Bretz, F., Miwa, T., Mi, X., Leisch, F., Scheipl, F., Bornkamp, B., Hothorn, T. (2012). Package 'mvtnorm'. URL http://CRAN.R-project.org, R package version 0.9-9992.
    • Hampson, L. V., Jennison, C. (2013). Group sequential tests for delayed responses. Journal of the Royal Statistical Society: Series B (Statistical Methodology) 75:1-37.
    • Jennison, C., Turnbull, B. (1993). Group sequential tests for bivariate response: Interim analyses of clinical trials with both efficacy and safety endpoints. Biometrics 49:741-752.
    • Julious, S. A., Mullee, M. A. (2008). Issues with using baseline in last observation carried forward analysis. Pharmaceutical Statistics 7:142-146.
    • Kelly, P. J., Stallard, N., Todd, S. (2005). An adaptive group sequential design for phase II/III clinical trials that select a single treatment from several. Journal of Biopharmaceutical Statistics 15:641-658.
    • Kimani, P. K., Stallard, N., Hutton, J. L. (2009). Dose selection in seamless phase ii/iii clinical trials based on efficacy and safety. Statistics in Medicine 28:917-936.
    • Koenig, F., Brannath, W., Bretz, F., Posch, M. (2008). Adaptive dunnett tests for treatment selection. Statistics in Medicine 27:1612-1625.
    • Lee, S. J., Kim, K., Tsiatis, A. A. (1996). Repeated significance testing in longitudinal clinical trials. Biometrika 83:779-789.
    • Lehmacher, W., Wassmer, G. (1999). Adaptive sample size calculations in group sequential trials. Biometrics 55(4):1286-1290.
    • Marcus, R., Peritz, E., Gabriel, K. R. (1976). On closed testing procedures with special reference to ordered analysis of variance. Biometrika 63(3):655-660.
    • Marschner, I., Becker, S. (2001). Interim monitoring of clinical trials based on long-term binary endpoints. Statistics in Medicine 20:177-192.
    • Posch, M., König, F., Branson, M., Brannath, W., Dunger-Baldauf, C., Bauer, P. (2005). Testing and estimation in flexible group sequential designs with adaptive treatment selection. Statistics in Medicine 24:3697-3714.
    • Schmoll, H., Cunnighmam, D., A., S., Krapetis, C., Rougier, P., Koski, S., P., B., Mookerjee, B., Robertson, J., van Cutsem, E. (2010). mFOLFOX6 + cediranib vs mFOLFOX6 + bevacizumab in previously untreated metastatic colorectal cancer (mcrc): A randomised, doubleblind, phase II/III study (HORIZON III). Ann. Oncol. 21(Supplement 8): vii189-vii224.
    • Sooriyarachchi, M., Whitehead, J., Whitehead, A., Bolland, K. (2006). The sequential analysis of repeated binary responses: A score test for the case of three time points. Statistics in Medicine 25:2196-2214.
    • Spiessens, B., Lesaffre, E., Verbeke, G., Kim, K., DeMets, D. L. (2000). An overview of group sequential methods in longitudinal clinical trials. Statistical Methods in Medical Research 19:497-515.
    • Stallard, N. (2010). A confirmatory seamless phase II/III clinical trial design incorporating short-term endpoint information. Statistics in Medicine 29:959-971.
    • Stallard, N., Todd, S. (2003). Sequential designs for phase III clinical trials incorporating treatment selection. Statistics in Medicine 22:689-703.
    • Stallard, N., Todd, S. (2011). Seamless phase II/III designs. Statistical Methods in Medical Research 20:623-634.
    • Todd, S., Stallard, N. (2005). A new clinical trial design combining phases II and III: Sequential designs with treatment selection and a change of endpoint. Drug Information Journal 39:109-118.
    • Westfall, P. H., Tobias, R. D., Wolfinger, R. D. (2011). Multiple Comparisons and Multiple Tests Using SAS. Cary, NC: SAS Institute Inc.
    • Whitehead, A., Sooriyarachchi, M., Whitehead, J., Bolland, K. (2008). Incorporating intermediate binary responses into interim analyses of clinical trials: A comparison of four methods. Statistics in Medicine 27:1646-1666.
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