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A response-adaptive randomization procedure for multi-armed clinical trials with normally distributed outcomes. (English) Zbl 1451.62147

Summary: We propose a novel response-adaptive randomization procedure for multi-armed trials with continuous outcomes that are assumed to be normally distributed. Our proposed rule is non-myopic, and oriented toward a patient benefit objective, yet maintains computational feasibility. We derive our response-adaptive algorithm based on the Gittins index for the multi-armed bandit problem, as a modification of the method first introduced in [S. S. Villar et al., Biometrics 71, No. 4, 969–978 (2015; Zbl 1419.62465)]. The resulting procedure can be implemented under the assumption of both known or unknown variance. We illustrate the proposed procedure by simulations in the context of phase II cancer trials. Our results show that, in a multi-armed setting, there are efficiency and patient benefit gains of using a response-adaptive allocation procedure with a continuous endpoint instead of a binary one. These gains persist even if an anticipated low rate of missing data due to deaths, dropouts, or complete responses is imputed online through a procedure first introduced in this paper. Additionally, we discuss how there are response-adaptive designs that outperform the traditional equal randomized design both in terms of efficiency and patient benefit measures in the multi-armed trial context.

MSC:

62P10 Applications of statistics to biology and medical sciences; meta analysis
62L05 Sequential statistical design
62K20 Response surface designs
62D10 Missing data
62D05 Sampling theory, sample surveys

Citations:

Zbl 1419.62465

References:

[1] Atkinson, A.C. and Biswas, A. (2013) Randomised Response‐Adaptive Designs in Clinical Trials. Boca Raton, FL: CRC Press. · Zbl 1284.62005
[2] Berry, D.A. (2011) Adaptive clinical trials: the promise and the caution. Journal of Clinical Oncology, 29(6), 606-609.
[3] Berry, D.A. and Fristedt, B. (1985) Bandit Problems: Sequential Allocation of Experiments, Monographs on Statistics and Applied Probability. London: Chapman & Hall. · Zbl 0659.62086
[4] Biswas, A. and Bhattacharya, R. (2009) Optimal response‐adaptive designs for normal responses. Biometrical Journal, 51(1), 193-202. · Zbl 1442.62269
[5] Biswas, A. and Bhattacharya, R. (2016) Response‐adaptive designs for continuous treatment responses in phase III clinical trials: a review. Statistical Methods in Medical Research, 25(1), 81-100.
[6] Coad, D.S. (1991a) Sequential estimation with data‐dependent allocation and time trends. Sequential Analysis, 10(1‐2), 91-97.
[7] Coad, D.S. (1991b) Sequential tests for an unstable response variable. Biometrika, 78(1), 113-121. · Zbl 0744.62110
[8] Coad, D.S. (1994) Estimation following sequential tests involving data‐dependent treatment allocation. Statistica Sinica, 4, 693-700. · Zbl 0824.60088
[9] Eisenhauer, E.A., Therasse, P., Bogaerts, J., Schwartz, L.H., Sargent, D., Ford, R.et al. (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European Journal of Cancer, 45(2), 228-247.
[10] Gittins, J., Glazebrook, K. and Weber, R. (2011) Multi‐armed Bandit Allocation Indices, 2nd edition. Chichester, UK: John Wiley & Sons Ltd. · Zbl 1401.90257
[11] Gwise, T.E., Zhou, J. and Hu, F. (2011) An optimal response adaptive biased coin design with \(k\) heteroscedastic treatments. Journal of Statistical Planning and Inference, 141(1), 235-242. · Zbl 1198.62072
[12] Hu, F. and Rosenberger, W.F. (2006) The Theory of Response‐Adaptive Randomization in Clinical Trials. Hoboken, NJ: John Wiley & Sons. · Zbl 1111.62107
[13] Hu, F. and Zhang, L.‐X. (2004) Asymptotic properties of doubly adaptive biased coin designs for multitreatment clinical trials. The Annals of Statistics, 32(1), 268-301. · Zbl 1105.62381
[14] Jaki, T., André, V., Su, T. and Whitehead, J. (2013) Designing exploratory cancer trials using change in tumour size as primary endpoint. Statistics in Medicine, 32(15), 2544-2554.
[15] Jones, D. (1975) Search procedures for industrial chemical research. PhD Thesis, University of Cambridge, Cambridge, UK. (accessed: March, 2018).
[16] Karrison, T.G., Maitland, M.L., Stadler, W.M. and Ratain, M.J. (2007) Design of phase II cancer trials using a continuous endpoint of change in tumor size: application to a study of sorafenib and erlotinib in non‐small‐cell lung cancer. Journal of the National Cancer Institute, 99(19), 1455-1461.
[17] Lavin, P.T. (1981) An alternative model for the evaluation of antitumor activity. Cancer Clinical Trials, 4(4), 451-457.
[18] Rosenberger, W.F. and Lachin, J.M. (2015) Randomization in Clinical Trials: Theory and Practice. Hoboken, NJ: John Wiley & Sons. · Zbl 1007.62091
[19] Royston, P., Altman, D.G. and Sauerbrei, W. (2006) Dichotomizing continuous predictors in multiple regression: a bad idea. Statistics in Medicine, 25(1), 127-141.
[20] Smith, A.L. and Villar, S.S. (2018) Bayesian adaptive bandit‐based designs using the Gittins index for multi‐armed trials with normally distributed endpoints. Journal of Applied Statistics, 45(6), 1052-1076. · Zbl 1516.62607
[21] Thall, P.F. and Wathen, J.K. (2007) Practical Bayesian adaptive randomisation in clinical trials. European Journal of Cancer, 43(5), 859-866.
[22] Thompson, W.R. (1933) On the likelihood that one unknown probability exceeds another in view of the evidence of two samples. Biometrika, 25(3/4), 285-294. · JFM 59.1159.03
[23] Trippa, L., Lee, E.Q., Wen, P.Y., Batchelor, T.T., Cloughesy, T., Parmigiani, G.et al. (2012) Bayesian adaptive randomized trial design for patients with recurrent glioblastoma. Journal of Clinical Oncology, 30(26), 3258.
[24] Villar, S.S., Bowden, J. and Wason, J. (2015a) Multi‐armed bandit models for the optimal design of clinical trials: benefits and challenges. Statistical Science, 30(2), 199-215. · Zbl 1332.62267
[25] Villar, S.S. and Rosenberger, W.F. (2018) Covariate‐adjusted response‐adaptive randomization for multi‐arm clinical trials using a modified forward looking Gittins index rule. Biometrics, 74(1), 49-57. · Zbl 1415.62141
[26] Villar, S.S., Wason, J. and Bowden, J. (2015b) Response‐adaptive randomization for multi‐arm clinical trials using the forward looking Gittins index rule. Biometrics, 71(4), 969-978. · Zbl 1419.62465
[27] Wang, Y.‐G. (1991a) Gittins indices and constrained allocation in clinical trials. Biometrika, 78(1), 101-111. · Zbl 0744.62109
[28] Wang, Y.‐G. (1991b) Sequential allocation in clinical trials. Communications in Statistics, 20(3), 791-805. · Zbl 0724.62077
[29] Wason, J.M and Trippa, L. (2014) A comparison of Bayesian adaptive randomization and multi‐stage designs for multi‐arm clinical trials. Statistics in Medicine, 33(13), 2206-2221.
[30] Wason, J.M. and Jaki, T. (2016) A review of statistical designs for improving the efficiency of phase II studies in oncology. Statistical Methods in Medical Research, 25(3), 1010-1021.
[31] Wason, J.M., Mander, A.P. and Eisen, T.G. (2011) Reducing sample sizes in two‐stage phase II cancer trials by using continuous tumour shrinkage end‐points. European Journal of Cancer, 47(7), 983-989.
[32] Williamson, S.F., Jacko, P., Villar, S.S. and Jaki, T. (2017) A Bayesian adaptive design for clinical trials in rare diseases. Computational Statistics and Data Analysis, 113, 136-153. · Zbl 1464.62183
[33] Zhang, L. and Rosenberger, W.F. (2006) Response‐adaptive randomization for clinical trials with continuous outcomes. Biometrics, 62(2), 562-569. · Zbl 1097.62139
[34] Zhang, L.‐X., Hu, F., Cheung, S.H. and Chan, W.S. (2011) Immigrated urn models—theoretical properties and applications. The Annals of Statistics, 39(1), 643-671. · Zbl 1226.60012
[35] Zhu, H. and Hu, F. (2009) Implementing optimal allocation for sequential continuous responses with multiple treatments. Journal of Statistical Planning and Inference, 139(7), 2420-2430. · Zbl 1160.62057
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