Application of adaptive randomization in clinical trials_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Yuning , XU Chang , ZOU Kang , LI Ling , DENG Ke ,  SUN Xin

Chinese Evidence-Based Medicine Center and CREAT Group, West China Hospital, Sichuan University, Chengdu 610041, P.R.China;

Corresponding author：

SUN Xin, Email: sunx79@hotmail.com

Keywords：

Adaptive randomization; Clinical trial; Restricted randomization; Response-adaptive randomization; Covariate-adaptive randomization

DOI：

10.7507/1672-2531.201910104

Video：

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Randomized controlled trial has been the "gold standard" for clinical trials, in which randomization serves as a fundamental principle of clinical trials and plays an important role in balancing covariates. The allocation probability in traditional design is fixed, while that in adaptive randomization can alter during the experiment according to the specified plan to achieve the purposes of balancing the sample size, maximizing the benefit of patient, or balancing covariates etc. In this study, the adaptive randomization methods applied in clinical trials are discussed to explore their advantages and disadvantages for providing reference for the randomization of clinical trials.

Citation： WANG Yuning, XU Chang, ZOU Kang, LI Ling, DENG Ke, SUN Xin. Application of adaptive randomization in clinical trials. Chinese Journal of Evidence-Based Medicine, 2020, 20(5): 616-620. doi: 10.7507/1672-2531.201910104 Copy

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2.	Sim J. Outcome-adaptive randomization in clinical trials: issues of participant welfare and autonomy. Theor Med Bioeth, 2019, 40(2): 83-101.
3.	Saville BR, Berry SM. Balanced covariates with response adaptive randomization. Pharm Stat, 2017, 16(3): 210-217.
4.	Lin J, Bunn V. Comparison of multi-arm multi-stage design and adaptive randomization in platform clinical trials. Contemp Clin Trials, 2017, 54: 48-59.
5.	Higham R, Tharmanathan P, Birks Y. Use and reporting of restricted randomization: a review. J Eval Clin Pract, 2015, 21(6): 1205-1211.
6.	Rosenberger WF, Sverdlov O, Hu F. Adaptive randomization for clinical trials. J Biopharm Stat, 2012, 22(4): 719-736.
7.	Vickers AJ. How to randomize. J Soc Integr Oncol, 2006, 4(4): 194-198.
8.	Kernan WN, Viscoli CM, Makuch RW, et al. Stratified randomization for clinical trials. J Clin Epidemiol, 1999, 52(1): 19-26.
9.	Antognini AB, Zagoraiou M. Balance and randomness in sequential clinical trials: the dominant biased coin design. Pharm Stat, 2014, 13(2): 119-127.
10.	Efron B. Forcing a sequential experiment to be balanced. Biometrika, 1971, 58(3): 403-417.
11.	Soares JF, Wu CFJ. Some Restricted randomization rules in sequential designs. Commun Stat Theory Methods, 1983, 12(17): 2017-2034.
12.	Yung-Pin C. Biased coin design with imbalance tolerance. Commun Biol, 1999, 15(5): 953-975.
13.	Smith R. Sequential treatment allocation using biased coin designs. J R Stat Soc Series B Stat Methodol, 1984, 46(3): 519-543.
14.	Wei LJ. The adaptive biased coin design for sequential experiments. Ann Statist, 1978, 6(1): 92-100.
15.	Atkinson AC. Optimum biased coin designs for sequential clinical trials with prognostic factors. Biometrika, 1982, 69(1): 61-67.
16.	Hu F, Rosenberger WF. The theory of response‐adaptive randomization in clinical trials. Hoboken: John Wiley & Sons, Inc., 2006.
17.	Lee JJ, Xuemin Gu, Suyu Liu. Bayesian adaptive randomization designs for targeted agent development. Clin Trials, 2010, 7(5): 584-596.
18.	Zelen M. Play the winner rule and the controlled clinical trial. J Am Stat Assoc, 1969, 64(325): 131-146.
19.	Wei LJ, Durham S. The randomized play-the-winner rule in medical trials. J Am Stat Assoc, 1978, 73(364): 840-843.
20.	Ivanova A. A play-the-winner-type urn design with reduced variability. Metrika, 2003, 58(1): 1-13.
21.	Melfi VF, Page C, Geraldes M. An adaptive randomized design with application to estimation. Can J Statist, 2001, 29(1): 107-116.
22.	FDA. Adaptive design clinical trials for drugs and biologics guidance for industry. Avaivale from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry.
23.	Thall PF, Wathen JK. Practical Bayesian adaptive randomisation in clinical trials. Eur J Cancer, 2007, 43(5): 859-866.
24.	Wathen JK, Thall PF. A simulation study of outcome adaptive randomization in multi-arm clinical trials. Clin Trials, 2017, 14(5): 432-440.
25.	Murphy P, Moline M, Mayleben D, et al. Lemborexant, a dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: Results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med, 2017, 13(11): 1289-1299.
26.	Maki RG, Wathen JK, Patel SR, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002[corrected]. J Clin Oncol, 2007, 25(19): 2755-2763.
27.	Du Y, Wang X, Jack Lee J. Simulation study for evaluating the performance of response-adaptive randomization. Contemp Clin Trials, 2015, 40: 15-25.
28.	Liu Z, Hu F, Zhang LX. Nonparametric response-adaptive randomization for continuous responses. Pharm Stat, 2018, 17(6): 781-796.
29.	Yin G, Chen N, Lee JJ. Phase II trial design with Bayesian adaptive randomization and predictive probability. J R Stat Soc Ser C Appl Stat, 2012, 61(2): 219-235.
30.	Antognini AB, Vagheggini A, Zagoraiou M. Is the classical Wald test always suitable under response-adaptive randomization? Stat Methods Med Res, 2016, 27(8): 2294-2311.
31.	Rosenberger WF, Sverdlov O. Handling covariates in the design of clinical trials. Statist Sci, 2008, 23(3): 404-419.
32.	Zagoraiou M. Choosing a covariate-adaptive randomization procedure in practice. J Biopharm Stat, 2017, 27(5): 845-857.
33.	Simon R. Patient subsets and variation in therapeutic efficacy. Br J Clin Pharmacol, 1982, 14(4): 473-482.
34.	Taves DR. Minimization: a new method of assigning patients to treatment and control groups. Clin Pharmacol Ther, 1974, 15(5): 443-453.
35.	Lin Y, Zhu M, Su Z. The pursuit of balance: An overview of covariate-adaptive randomization techniques in clinical trials. Contemp Clin Trials, 2015, 45(Pt A): 21-25.
36.	Altman DG, Schulz KF, Moher D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med, 2001, 134(8): 663-694.
37.	Aftab RA, Khan AH, Adnan AS, et al. Safety and efficacy of Losartan 50 mg in reducing blood pressure among patients with post-dialysis euvolemic hypertension: a randomized control trial. Sci Rep, 2017, 7(1): 17741.
38.	Ciolino J, Zhao W, Martin R, et al. Quantifying the cost in power of ignoring continuous covariate imbalances in clinical trial randomization. Contemp Clin Trials, 2011, 32(2): 250-259.
39.	Hu J, Zhu H, Hu F. A unified family of covariate-adjusted response-adaptive designs based on efficiency and ethics. J Am Stat Assoc, 2015, 110(509): 357-367.
40.	Bandyopadhyay U, Bhattacharya R. A covariate-adjusted response-adaptive allocation in clinical trials for a general class of responses. Stat Med, 2013, 32(29): 5053-5061.
41.	Biswas A, Bhattacharya R, Park E. On a class of optimal covariate-adjusted response adaptive designs for survival outcomes. Stat Methods Med Res, 2016, 25(6): 2444-2456.
42.	Atkinson AC, Biswas A. Adaptive biased-coin designs for skewing the allocation proportion in clinical trials with normal responses. Stat Med, 2005, 24(16): 2477-2492.
43.	Rosenberger WF, Vidyashankar AN, Agarwal DK. Covariate-adjusted response-adaptive designs for binary response. J Biopharm Stat, 2001, 11(4): 227-236.
44.	Zhu H, Hu F. Implementing optimal allocation for sequential continuous responses with multiple treatments. J Stat Plan Inference, 2009, 139(7): 2420-2430.
45.	Zhang LX, Hu F, Cheung SH, et al. Immigrated urn models - asymptotic properties and applications. Ann Stat, 2008, 39(1): 643-671.
46.	Bugni FA, Canay IA, Shaikh AM. Inference under covariate-adaptive randomization. J Am Stat Assoc, 2018, 113(524): 1784-1796.

1. Moher D, Hopewell S, Schulz KF, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ, 2010, 340: c869.
2. Sim J. Outcome-adaptive randomization in clinical trials: issues of participant welfare and autonomy. Theor Med Bioeth, 2019, 40(2): 83-101.
3. Saville BR, Berry SM. Balanced covariates with response adaptive randomization. Pharm Stat, 2017, 16(3): 210-217.
4. Lin J, Bunn V. Comparison of multi-arm multi-stage design and adaptive randomization in platform clinical trials. Contemp Clin Trials, 2017, 54: 48-59.
5. Higham R, Tharmanathan P, Birks Y. Use and reporting of restricted randomization: a review. J Eval Clin Pract, 2015, 21(6): 1205-1211.
6. Rosenberger WF, Sverdlov O, Hu F. Adaptive randomization for clinical trials. J Biopharm Stat, 2012, 22(4): 719-736.
7. Vickers AJ. How to randomize. J Soc Integr Oncol, 2006, 4(4): 194-198.
8. Kernan WN, Viscoli CM, Makuch RW, et al. Stratified randomization for clinical trials. J Clin Epidemiol, 1999, 52(1): 19-26.
9. Antognini AB, Zagoraiou M. Balance and randomness in sequential clinical trials: the dominant biased coin design. Pharm Stat, 2014, 13(2): 119-127.
10. Efron B. Forcing a sequential experiment to be balanced. Biometrika, 1971, 58(3): 403-417.
11. Soares JF, Wu CFJ. Some Restricted randomization rules in sequential designs. Commun Stat Theory Methods, 1983, 12(17): 2017-2034.
12. Yung-Pin C. Biased coin design with imbalance tolerance. Commun Biol, 1999, 15(5): 953-975.
13. Smith R. Sequential treatment allocation using biased coin designs. J R Stat Soc Series B Stat Methodol, 1984, 46(3): 519-543.
14. Wei LJ. The adaptive biased coin design for sequential experiments. Ann Statist, 1978, 6(1): 92-100.
15. Atkinson AC. Optimum biased coin designs for sequential clinical trials with prognostic factors. Biometrika, 1982, 69(1): 61-67.
16. Hu F, Rosenberger WF. The theory of response‐adaptive randomization in clinical trials. Hoboken: John Wiley & Sons, Inc., 2006.
17. Lee JJ, Xuemin Gu, Suyu Liu. Bayesian adaptive randomization designs for targeted agent development. Clin Trials, 2010, 7(5): 584-596.
18. Zelen M. Play the winner rule and the controlled clinical trial. J Am Stat Assoc, 1969, 64(325): 131-146.
19. Wei LJ, Durham S. The randomized play-the-winner rule in medical trials. J Am Stat Assoc, 1978, 73(364): 840-843.
20. Ivanova A. A play-the-winner-type urn design with reduced variability. Metrika, 2003, 58(1): 1-13.
21. Melfi VF, Page C, Geraldes M. An adaptive randomized design with application to estimation. Can J Statist, 2001, 29(1): 107-116.
22. FDA. Adaptive design clinical trials for drugs and biologics guidance for industry. Avaivale from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry.
23. Thall PF, Wathen JK. Practical Bayesian adaptive randomisation in clinical trials. Eur J Cancer, 2007, 43(5): 859-866.
24. Wathen JK, Thall PF. A simulation study of outcome adaptive randomization in multi-arm clinical trials. Clin Trials, 2017, 14(5): 432-440.
25. Murphy P, Moline M, Mayleben D, et al. Lemborexant, a dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: Results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med, 2017, 13(11): 1289-1299.
26. Maki RG, Wathen JK, Patel SR, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002[corrected]. J Clin Oncol, 2007, 25(19): 2755-2763.
27. Du Y, Wang X, Jack Lee J. Simulation study for evaluating the performance of response-adaptive randomization. Contemp Clin Trials, 2015, 40: 15-25.
28. Liu Z, Hu F, Zhang LX. Nonparametric response-adaptive randomization for continuous responses. Pharm Stat, 2018, 17(6): 781-796.
29. Yin G, Chen N, Lee JJ. Phase II trial design with Bayesian adaptive randomization and predictive probability. J R Stat Soc Ser C Appl Stat, 2012, 61(2): 219-235.
30. Antognini AB, Vagheggini A, Zagoraiou M. Is the classical Wald test always suitable under response-adaptive randomization? Stat Methods Med Res, 2016, 27(8): 2294-2311.
31. Rosenberger WF, Sverdlov O. Handling covariates in the design of clinical trials. Statist Sci, 2008, 23(3): 404-419.
32. Zagoraiou M. Choosing a covariate-adaptive randomization procedure in practice. J Biopharm Stat, 2017, 27(5): 845-857.
33. Simon R. Patient subsets and variation in therapeutic efficacy. Br J Clin Pharmacol, 1982, 14(4): 473-482.
34. Taves DR. Minimization: a new method of assigning patients to treatment and control groups. Clin Pharmacol Ther, 1974, 15(5): 443-453.
35. Lin Y, Zhu M, Su Z. The pursuit of balance: An overview of covariate-adaptive randomization techniques in clinical trials. Contemp Clin Trials, 2015, 45(Pt A): 21-25.
36. Altman DG, Schulz KF, Moher D, et al. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med, 2001, 134(8): 663-694.
37. Aftab RA, Khan AH, Adnan AS, et al. Safety and efficacy of Losartan 50 mg in reducing blood pressure among patients with post-dialysis euvolemic hypertension: a randomized control trial. Sci Rep, 2017, 7(1): 17741.
38. Ciolino J, Zhao W, Martin R, et al. Quantifying the cost in power of ignoring continuous covariate imbalances in clinical trial randomization. Contemp Clin Trials, 2011, 32(2): 250-259.
39. Hu J, Zhu H, Hu F. A unified family of covariate-adjusted response-adaptive designs based on efficiency and ethics. J Am Stat Assoc, 2015, 110(509): 357-367.
40. Bandyopadhyay U, Bhattacharya R. A covariate-adjusted response-adaptive allocation in clinical trials for a general class of responses. Stat Med, 2013, 32(29): 5053-5061.
41. Biswas A, Bhattacharya R, Park E. On a class of optimal covariate-adjusted response adaptive designs for survival outcomes. Stat Methods Med Res, 2016, 25(6): 2444-2456.
42. Atkinson AC, Biswas A. Adaptive biased-coin designs for skewing the allocation proportion in clinical trials with normal responses. Stat Med, 2005, 24(16): 2477-2492.
43. Rosenberger WF, Vidyashankar AN, Agarwal DK. Covariate-adjusted response-adaptive designs for binary response. J Biopharm Stat, 2001, 11(4): 227-236.
44. Zhu H, Hu F. Implementing optimal allocation for sequential continuous responses with multiple treatments. J Stat Plan Inference, 2009, 139(7): 2420-2430.
45. Zhang LX, Hu F, Cheung SH, et al. Immigrated urn models - asymptotic properties and applications. Ann Stat, 2008, 39(1): 643-671.
46. Bugni FA, Canay IA, Shaikh AM. Inference under covariate-adaptive randomization. J Am Stat Assoc, 2018, 113(524): 1784-1796.

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