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

Authors：

WANG Yuning , XU Chang , DENG Ke , LI Ling ,  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 design; Clinical trial; Adaptive randomization; Group sequential design

DOI：

10.7507/1672-2531.201910103

Video：

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Due to the competition of new drug research and clinical requirement, speeding up drug development and marketing requires faster and more flexible clinical trial design that meets the ethical requirements. Different adaptive designs have emerged in clinical trials of different stages and purposes, for trial efficiency improvement. Adaptive design is more widely used in the field of oncology. Compared with traditional design, adaptive design is more complicated and requires higher level of methodology from researchers. Therefore, implementing adaptive design requires careful consideration and adequate preparation. This paper aims to summarize the design of adaptive methods used in different trial stages so as to provide reference for clinical research designers and implementers.

Citation： WANG Yuning, XU Chang, DENG Ke, LI Ling, SUN Xin. Application of adaptive design in clinical trials. Chinese Journal of Evidence-Based Medicine, 2020, 20(4): 487-491. doi: 10.7507/1672-2531.201910103 Copy

1.	Food and Drug Administration. Adaptive design clinical trials for drugs and biologics guidance for industry. 2019. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry.
2.	Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst, 2009, 101(10): 708-720.
3.	Marchenko O, Fedorov V, Lee JJ, et al. Adaptive clinical trials: overview of early-phase designs and challenges. Ther Innov Regul Sci, 2014, 48(1): 20-30.
4.	Sato A, Shimura M, Gosho M. Practical characteristics of adaptive design in phase 2 and 3 clinical trials. J Clin Pharm Ther, 2018, 43(2): 170-180.
5.	Korn EL, Freidlin B. Adaptive clinical trials: advantages and disadvantages of various adaptive design elements. J Natl Cancer Inst, 2017, 109(6): djx013.
6.	Maca J, Dragalin V, Gallo P. Adaptive clinical trials: overview of phase III designs and challenges. Ther Innov Regul Sci, 2014, 48(1): 31-40.
7.	Simon N, Simon R. Adaptive enrichment designs for clinical trials. Biostatistics, 2013, 14(4): 613-625.
8.	Wheeler GM, Mander AP, Bedding A, et al. How to design a dose-finding study using the continual reassessment method. BMC Med Res Methodol, 2019, 19(1): 18.
9.	Mason AJ, Gonzalez-Maffe J, Quinn K, et al. Developing a bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment. Stat Med, 2017, 36(5): 754-771.
10.	Yuan Y, Hess KR, Hilsenbeck SG, et al. Bayesian optimal interval design: a simple and well-performing design for phase I oncology trials. Clin Cancer Res, 2016, 22(17): 4291-4301.
11.	Paoletti X, Ezzalfani M, Le Tourneau C. Statistical controversies in clinical research: requiem for the 3+3 design for phase I trials. Ann Oncol, 2015, 26(9): 1808-1812.
12.	Storer BE. An evaluation of phase I clinical trial designs in the continuous dose-response setting. Stat Med, 2001, 20(16): 2399-2408.
13.	Love SB, Brown S, Weir CJ, et al. Embracing model-based designs for dose-finding trials. Br J Cancer, 2017, 117(3): 332-339.
14.	van Brummelen EM, Huitema AD, van Werkhoven E, et al. The performance of model-based versus rule-based phase I clinical trials in oncology : A quantitative comparison of the performance of model-based versus rule-based phase I trials with molecularly targeted anticancer drugs over the last 2 years. J Pharmacokinet Pharmacodyn, 2016, 43(3): 235-242.
15.	Liu H, Lin X, Huang X. An oncology clinical trial design with randomization adaptive to both short- and long-term responses. Stat Methods Med Res, 2019, 28(7): 2015-2031.
16.	Wathen JK, Thall PF. A simulation study of outcome adaptive randomization in multi-arm clinical trials. Clin Trials, 2017, 14(5): 432-440.
17.	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.
18.	Yin G, Chen N, Lee JJ. Bayesian adaptive randomization and trial monitoring with predictive probability for time-to-event endpoint. Stat Biosci, 2018, 10(2): 420-438.
19.	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.
20.	Mütze T, Glimm E, Schmidli H, et al. Group sequential designs with robust semiparametric recurrent event models. Stat Methods Med Res, 2019, 28(8): 2385-2403.
21.	Neumann K, Grittner U, Piper SK, et al. Increasing efficiency of preclinical research by group sequential designs. PLoS Biol, 2017, 15(3): e2001307.
22.	Dupuis L, Dengler R, Heneka MT, et al. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLoS One, 2012, 7(6): e37885.
23.	Urach S, Posch M. Multi-arm group sequential designs with a simultaneous stopping rule. Stat Med, 2016, 35(30): 5536-5550.
24.	Trippa L, Alexander BM. Bayesian baskets: a novel design for biomarker-based clinical trials. J Clin Oncol, 2017, 35(6): 681-687.
25.	Zang Y, Guo B. Optimal two-stage enrichment design correcting for biomarker misclassification. Stat Methods Med Res, 2018, 27(1): 35-47.
26.	Barker AD, Sigman CC, Kelloff GJ, et al. I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther, 2009, 86(1): 97-100.
27.	Kim ES, Herbst RS, Wistuba II, et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov, 2011, 1(1): 44-53.
28.	Antoniou M, Jorgensen AL, Kolamunnage-Dona R. Biomarker-guided adaptive trial designs in Phase II and Phase III: a methodological review. PLoS One, 2016, 11(2): e0149803.
29.	Freidlin B, Korn EL. Biomarker enrichment strategies: matching trial design to biomarker credentials. Nat Rev Clin Oncol, 2014, 11(2): 81-90.
30.	Bretz F, Schmidli H, König F, et al. Confirmatory seamless phase II/III clinical trials with hypotheses selection at interim: general concepts. Biom J, 2006, 48(4): 623-634.
31.	Cerqueira FP, Jesus AMC, Cotrim MD. Adaptive design: a review of the technical, statistical, and regulatory aspects of implementation in a clinical trial. Ther Innov Regul Sci, 2019.
32.	Lai TL, Lavori PW, Tsang KW. Adaptive design of confirmatory trials: Advances and challenges. Contemp Clin Trials, 2015, 45(Pt A): 93-102.
33.	Geiger MJ, Skrivanek Z, Gaydos B, et al. An adaptive, dose-finding, seamless phase 2/3 study of a long-acting glucagon-like peptide-1 analog (dulaglutide): trial design and baseline characteristics. J Diabetes Sci Technol, 2012, 6(6): 1319-1327.
34.	Pan H, Huang P, Wang Z, et al. A novel Bayesian seamless phase I/II design. PLoS One, 2013, 8(9): e73060.
35.	Yan D, Wages NA, Dressler EV. Improved adaptive randomization strategies for a seamless Phase I/II dose-finding design. J Biopharm Stat, 2019, 29(2): 333-347.
36.	Yuan J, Pang H, Tong T, et al. Seamless Phase IIa/IIb and enhanced dose-finding adaptive design. J Biopharm Stat, 2016, 26(5): 912-923.
37.	Thall PF. A review of phase 2-3 clinical trial designs. Lifetime Data Anal, 2008, 14(1): 37-53.
38.	Cui L, Zhang L, Yang B. Optimal adaptive group sequential design with flexible timing of sample size determination. Contemp Clin Trials, 2017, 63: 8-12.
39.	Mütze T, Schmidli H, Friede T. Sample size re-estimation incorporating prior information on a nuisance parameter. Pharm Stat, 2018, 17(2): 126-143.
40.	Chung JW, Kim SJ, Hwang J, et al. Comparison of Clopidogrel and Ticlopidine/Ginkgo Biloba in patients with Clopidogrel resistance and carotid stenting. Front Neurol, 2019, 10: 44.
41.	Ando Y, Hirakawa A, Uyama Y. Adaptive clinical trials for new drug applications in Japan. Eur Neuropsychopharmacol, 2011, 21(2): 175-179.
42.	Berry DA. Adaptive clinical trials: the promise and the caution. J Clin Oncol, 2011, 29(6): 606-609.
43.	Zang Y, Lee JJ. Adaptive clinical trial designs in oncology. Chin Clin Oncol, 2014, 3(4): 49.

1. Food and Drug Administration. Adaptive design clinical trials for drugs and biologics guidance for industry. 2019. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry.
2. Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst, 2009, 101(10): 708-720.
3. Marchenko O, Fedorov V, Lee JJ, et al. Adaptive clinical trials: overview of early-phase designs and challenges. Ther Innov Regul Sci, 2014, 48(1): 20-30.
4. Sato A, Shimura M, Gosho M. Practical characteristics of adaptive design in phase 2 and 3 clinical trials. J Clin Pharm Ther, 2018, 43(2): 170-180.
5. Korn EL, Freidlin B. Adaptive clinical trials: advantages and disadvantages of various adaptive design elements. J Natl Cancer Inst, 2017, 109(6): djx013.
6. Maca J, Dragalin V, Gallo P. Adaptive clinical trials: overview of phase III designs and challenges. Ther Innov Regul Sci, 2014, 48(1): 31-40.
7. Simon N, Simon R. Adaptive enrichment designs for clinical trials. Biostatistics, 2013, 14(4): 613-625.
8. Wheeler GM, Mander AP, Bedding A, et al. How to design a dose-finding study using the continual reassessment method. BMC Med Res Methodol, 2019, 19(1): 18.
9. Mason AJ, Gonzalez-Maffe J, Quinn K, et al. Developing a bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment. Stat Med, 2017, 36(5): 754-771.
10. Yuan Y, Hess KR, Hilsenbeck SG, et al. Bayesian optimal interval design: a simple and well-performing design for phase I oncology trials. Clin Cancer Res, 2016, 22(17): 4291-4301.
11. Paoletti X, Ezzalfani M, Le Tourneau C. Statistical controversies in clinical research: requiem for the 3+3 design for phase I trials. Ann Oncol, 2015, 26(9): 1808-1812.
12. Storer BE. An evaluation of phase I clinical trial designs in the continuous dose-response setting. Stat Med, 2001, 20(16): 2399-2408.
13. Love SB, Brown S, Weir CJ, et al. Embracing model-based designs for dose-finding trials. Br J Cancer, 2017, 117(3): 332-339.
14. van Brummelen EM, Huitema AD, van Werkhoven E, et al. The performance of model-based versus rule-based phase I clinical trials in oncology : A quantitative comparison of the performance of model-based versus rule-based phase I trials with molecularly targeted anticancer drugs over the last 2 years. J Pharmacokinet Pharmacodyn, 2016, 43(3): 235-242.
15. Liu H, Lin X, Huang X. An oncology clinical trial design with randomization adaptive to both short- and long-term responses. Stat Methods Med Res, 2019, 28(7): 2015-2031.
16. Wathen JK, Thall PF. A simulation study of outcome adaptive randomization in multi-arm clinical trials. Clin Trials, 2017, 14(5): 432-440.
17. 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.
18. Yin G, Chen N, Lee JJ. Bayesian adaptive randomization and trial monitoring with predictive probability for time-to-event endpoint. Stat Biosci, 2018, 10(2): 420-438.
19. 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.
20. Mütze T, Glimm E, Schmidli H, et al. Group sequential designs with robust semiparametric recurrent event models. Stat Methods Med Res, 2019, 28(8): 2385-2403.
21. Neumann K, Grittner U, Piper SK, et al. Increasing efficiency of preclinical research by group sequential designs. PLoS Biol, 2017, 15(3): e2001307.
22. Dupuis L, Dengler R, Heneka MT, et al. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLoS One, 2012, 7(6): e37885.
23. Urach S, Posch M. Multi-arm group sequential designs with a simultaneous stopping rule. Stat Med, 2016, 35(30): 5536-5550.
24. Trippa L, Alexander BM. Bayesian baskets: a novel design for biomarker-based clinical trials. J Clin Oncol, 2017, 35(6): 681-687.
25. Zang Y, Guo B. Optimal two-stage enrichment design correcting for biomarker misclassification. Stat Methods Med Res, 2018, 27(1): 35-47.
26. Barker AD, Sigman CC, Kelloff GJ, et al. I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther, 2009, 86(1): 97-100.
27. Kim ES, Herbst RS, Wistuba II, et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov, 2011, 1(1): 44-53.
28. Antoniou M, Jorgensen AL, Kolamunnage-Dona R. Biomarker-guided adaptive trial designs in Phase II and Phase III: a methodological review. PLoS One, 2016, 11(2): e0149803.
29. Freidlin B, Korn EL. Biomarker enrichment strategies: matching trial design to biomarker credentials. Nat Rev Clin Oncol, 2014, 11(2): 81-90.
30. Bretz F, Schmidli H, König F, et al. Confirmatory seamless phase II/III clinical trials with hypotheses selection at interim: general concepts. Biom J, 2006, 48(4): 623-634.
31. Cerqueira FP, Jesus AMC, Cotrim MD. Adaptive design: a review of the technical, statistical, and regulatory aspects of implementation in a clinical trial. Ther Innov Regul Sci, 2019.
32. Lai TL, Lavori PW, Tsang KW. Adaptive design of confirmatory trials: Advances and challenges. Contemp Clin Trials, 2015, 45(Pt A): 93-102.
33. Geiger MJ, Skrivanek Z, Gaydos B, et al. An adaptive, dose-finding, seamless phase 2/3 study of a long-acting glucagon-like peptide-1 analog (dulaglutide): trial design and baseline characteristics. J Diabetes Sci Technol, 2012, 6(6): 1319-1327.
34. Pan H, Huang P, Wang Z, et al. A novel Bayesian seamless phase I/II design. PLoS One, 2013, 8(9): e73060.
35. Yan D, Wages NA, Dressler EV. Improved adaptive randomization strategies for a seamless Phase I/II dose-finding design. J Biopharm Stat, 2019, 29(2): 333-347.
36. Yuan J, Pang H, Tong T, et al. Seamless Phase IIa/IIb and enhanced dose-finding adaptive design. J Biopharm Stat, 2016, 26(5): 912-923.
37. Thall PF. A review of phase 2-3 clinical trial designs. Lifetime Data Anal, 2008, 14(1): 37-53.
38. Cui L, Zhang L, Yang B. Optimal adaptive group sequential design with flexible timing of sample size determination. Contemp Clin Trials, 2017, 63: 8-12.
39. Mütze T, Schmidli H, Friede T. Sample size re-estimation incorporating prior information on a nuisance parameter. Pharm Stat, 2018, 17(2): 126-143.
40. Chung JW, Kim SJ, Hwang J, et al. Comparison of Clopidogrel and Ticlopidine/Ginkgo Biloba in patients with Clopidogrel resistance and carotid stenting. Front Neurol, 2019, 10: 44.
41. Ando Y, Hirakawa A, Uyama Y. Adaptive clinical trials for new drug applications in Japan. Eur Neuropsychopharmacol, 2011, 21(2): 175-179.
42. Berry DA. Adaptive clinical trials: the promise and the caution. J Clin Oncol, 2011, 29(6): 606-609.
43. Zang Y, Lee JJ. Adaptive clinical trial designs in oncology. Chin Clin Oncol, 2014, 3(4): 49.

Chinese Journal of Evidence-Based Medicine

Application of adaptive design in clinical trials

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