Application of research methods of master protocol in precision medicine_Chinese Journal of Evidence-Based Medicine

Authors：

SUN Yuan ^1,2 ,  ZHANG Ling ^1,2

1. Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing 100069, P. R. China;
2. Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing 100069, P. R. China;

Corresponding author：

ZHANG Ling, Email: zlilyepi@ccmu.edu.cn

Keywords：

Precision medicine; Master protocol; Basket trial; Umbrella trial; Platform trial

DOI：

10.7507/1672-2531.202212111

Video：

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Precision medicine is an individualized clinical research model established according to gene, environment, lifestyle and other information. As an innovative method of clinical trials, the main scheme design breaks the barriers of traditional randomized controlled trials to the evaluation of targeted therapies in precision medicine and improves the efficiency of clinical research. This paper will systematically introduce the types, concepts and principles of the main scheme design of the new method of precision medicine clinical trial design, and summarize the advantages and limitations of the main scheme design combined with classic cases, aiming at providing scientific and rigorous methodological guidance and clinical practice experience for precision medicine scientific research design.

Citation： SUN Yuan, ZHANG Ling. Application of research methods of master protocol in precision medicine. Chinese Journal of Evidence-Based Medicine, 2023, 23(4): 465-470. doi: 10.7507/1672-2531.202212111 Copy

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7.	毛元铭, 詹瑨祺, 王榕榕, 等. 临床医学试验主方案概述及其应用. 中国新药杂志, 2021, 30(22): 2083-2090.
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9.	Hirakawa A, Asano J, Sato H, et al. Master protocol trials in oncology: review and new trial designs. Contemp Clin Trials Commun, 2018, 12: 1-8.
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29.	Li BT, Shen R, Buonocore D, et al. Ado-trastuzumab emtansine for patients with her2-mutant lung cancers: results from a phase ii basket trial. J Clin Oncol, 2018, 36(24): 2532-2537.
30.	高珺, 苏丽文, 袁鹰, 等. 抗肿瘤药物主方案试验设计进展及统计考量. 中国卫生统计, 2021, 38(6): 950-955.
31.	Menis J, Hasan B, Besse B. New clinical research strategies in thoracic oncology: clinical trial design, adaptive, basket and umbrella trials, new end-points and new evaluations of response. Eur Respir Rev, 2014, 23(133): 367-378.
32.	Eu Clinical Trials Register. Phase II study of PHA-739358 administered by a 24-hour IV infusion every 14 days in advanced/metastatic breast, ovarian, colorectal, pancreatic, small cell lung and non small cell lung cancers.
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34.	Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med, 2010, 363(9): 809-819.
35.	Pardanani A, Tefferi A. BRAF mutations in hairy-cell leukemia. N Engl J Med, 2011, 365(10): 961.
36.	Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature, 2012, 483(7387): 100-103.
37.	于亚南, 杜培艳, 刘骏, 等. 精准医学创新性临床试验设计"主方案"研究的概念、设计与案例. 中国新药杂志, 2020, 29(23): 2712-2717.
38.	钱真真, 周莎, 于亚南, 等. 适应性随机化及其在临床试验中的应用操作要点. 中国循证医学杂志, 2022, 22(8): 971-977.
39.	衡明莉, 王北琪, 王骏. 对美国FDA适应性设计指导原则的介绍. 中国临床药理学杂志, 2019, 35(12): 1316-1320.
40.	The I-SPY 2 trials.
41.	Pusztai L, Yau C, Wolf DM, et al. Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. Cancer Cell, 2021, 39(7): 989-998.
42.	Tang R, Shen J, Yuan Y. ComPAS: a Bayesian drug combination platform trial design with adaptive shrinkage. Stat Med, 2019, 38(7): 1120-1134.
43.	Clinicaltrials. Gov. Randomized, embedded, multifactorial adaptive platform trial for community- acquired pneumonia (REMAP-CAP).
44.	Bateman RJ, Benzinger TL, Berry S, et al. The DIAN-TU next generation alzheimer's prevention trial: adaptive design and disease progression model. Alzheimers Dement, 2017, 13(1): 8-19.
45.	Davey RT, Jr. , Dodd L, Proschan MA, et al. A randomized, controlled trial of zmapp for ebola virus infection. N Engl J Med, 2016, 375(15): 1448-1456.
46.	郭晓慧, 黄仟, 谢雁鸣, 等. 伞式设计与篮式设计在中医药循证评价中的应用. 中国中药杂志, 2021, 46(8): 2010-2015.
47.	张雯雯, 陈润生院士. 从新冠病毒、精准医学到核酸药物. 高科技与产业化, 2020, 10: 28-31.

1. 赵晓宇, 刁天喜, 高云华, 等. 美国“精准医学计划”解读与思考. 军事医学, 2015, (4): 241-244.
2. White house. President Obama's state of the union address-remarks as prepared for delivery.
3. White house. Fact sheet: president Obama's precision medicine initiative.
4. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med, 2015, 372(9): 793-795.
5. 吴家睿. 精确医学5年历程的回顾与思考(上). 医学与哲学, 2021, 42(20): 1-4,10.
6. 关之玥, 刘岩, 张晶晶, 等. 母方案平台试验设计方法及其在相关领域中的应用. 中国循证医学杂志, 2021, 21(8): 986-992.
7. 毛元铭, 詹瑨祺, 王榕榕, 等. 临床医学试验主方案概述及其应用. 中国新药杂志, 2021, 30(22): 2083-2090.
8. Redman MW, Allegra CJ. The master protocol concept. Semin Oncol, 2015, 42(5): 724-730.
9. Hirakawa A, Asano J, Sato H, et al. Master protocol trials in oncology: review and new trial designs. Contemp Clin Trials Commun, 2018, 12: 1-8.
10. Woodcock J, LaVange LM. Master protocols to study multiple therapies, multiple diseases, or both. N Engl J Med, 2017, 377(1): 62-70.
11. U. S. Food and Drug Administration. Master protocols: efficient clinical trial design strategies to expedite development of oncology drugs and biologics guidance for industry.
12. U. S. Food and Drug Administration. Adaptive designs for medical device clinical studies guidance for industry and food and drug administration staff.
13. 国家药品监督管理局药品审评中心. 药物临床试验适应性设计指导原则(试行).
14. 国家药品监督管理局药品审评中心. 抗肿瘤药物临床试验统计学设计指导原则(试行).
15. Park JJH, Siden E, Zoratti MJ, et al. Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols. Trials, 2019, 20(1): 572.
16. Heinrich MC, Joensuu H, Demetri GD, et al. Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases. Clin Cancer Res, 2008, 14(9): 2717-2725.
17. Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med, 2015, 373(8): 726-736.
18. Clinicaltrials. Gov. Phase 2 study assessing efficacy and safety of crizotinib in patients harboring an alteration on ALK, MET or ROS1 (AcSe´).
19. Hainsworth JD, Meric-Bernstam F, Swanton C, et al. Targeted therapy for advanced solid tumors on the basis of molecular profiles: results from mypathway, an open-label, phase iia multiple basket study. J Clin Oncol, 2018, 36(6): 536-542.
20. Javle M, Borad MJ, Azad NS, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol, 2021, 22(9): 1290-1300.
21. Kim ES, Herbst RS, Wistuba II, et al. The BATTLE trial: personalizing therapy for lung cancer. Cancer Discov, 2011, 1(1): 44-53.
22. Redman MW, Papadimitrakopoulou VA, Minichiello K, et al. Biomarker-driven therapies for previously treated squamous non-small-cell lung cancer (Lung-MAP SWOG S1400): a biomarker-driven master protocol. Lancet Oncol, 2020, 21(12): 1589-1601.
23. Alden RS, Mandrekar SJ, Oxnard GR. Designing a definitive trial for adjuvant targeted therapy in genotype defined lung cancer: the ALCHEMIST trials. Chin Clin Oncol, 2015, 4(3): 37.
24. 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.
25. Berry SM, Connor JT, Lewis RJ. The platform trial: an efficient strategy for evaluating multiple treatments. JAMA, 2015, 313(16): 1619-1620.
26. RECOVERY Central Coordinating Office. RECOVERY protocol V1.0.
27. Park JJH, Hsu G, Siden EG, et al. An overview of precision oncology basket and umbrella trials for clinicians. CA Cancer J Clin, 2020, 70(2): 125-137.
28. Redig AJ, Jänne PA. Basket trials and the evolution of clinical trial design in an era of genomic medicine. J Clin Oncol, 2015, 33(9): 975-977.
29. Li BT, Shen R, Buonocore D, et al. Ado-trastuzumab emtansine for patients with her2-mutant lung cancers: results from a phase ii basket trial. J Clin Oncol, 2018, 36(24): 2532-2537.
30. 高珺, 苏丽文, 袁鹰, 等. 抗肿瘤药物主方案试验设计进展及统计考量. 中国卫生统计, 2021, 38(6): 950-955.
31. Menis J, Hasan B, Besse B. New clinical research strategies in thoracic oncology: clinical trial design, adaptive, basket and umbrella trials, new end-points and new evaluations of response. Eur Respir Rev, 2014, 23(133): 367-378.
32. Eu Clinical Trials Register. Phase II study of PHA-739358 administered by a 24-hour IV infusion every 14 days in advanced/metastatic breast, ovarian, colorectal, pancreatic, small cell lung and non small cell lung cancers.
33. Clinicaltrials. Gov. CREATE: cross-tumoral phase 2 with crizotinib.
34. Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med, 2010, 363(9): 809-819.
35. Pardanani A, Tefferi A. BRAF mutations in hairy-cell leukemia. N Engl J Med, 2011, 365(10): 961.
36. Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature, 2012, 483(7387): 100-103.
37. 于亚南, 杜培艳, 刘骏, 等. 精准医学创新性临床试验设计"主方案"研究的概念、设计与案例. 中国新药杂志, 2020, 29(23): 2712-2717.
38. 钱真真, 周莎, 于亚南, 等. 适应性随机化及其在临床试验中的应用操作要点. 中国循证医学杂志, 2022, 22(8): 971-977.
39. 衡明莉, 王北琪, 王骏. 对美国FDA适应性设计指导原则的介绍. 中国临床药理学杂志, 2019, 35(12): 1316-1320.
40. The I-SPY 2 trials.
41. Pusztai L, Yau C, Wolf DM, et al. Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. Cancer Cell, 2021, 39(7): 989-998.
42. Tang R, Shen J, Yuan Y. ComPAS: a Bayesian drug combination platform trial design with adaptive shrinkage. Stat Med, 2019, 38(7): 1120-1134.
43. Clinicaltrials. Gov. Randomized, embedded, multifactorial adaptive platform trial for community- acquired pneumonia (REMAP-CAP).
44. Bateman RJ, Benzinger TL, Berry S, et al. The DIAN-TU next generation alzheimer's prevention trial: adaptive design and disease progression model. Alzheimers Dement, 2017, 13(1): 8-19.
45. Davey RT, Jr. , Dodd L, Proschan MA, et al. A randomized, controlled trial of zmapp for ebola virus infection. N Engl J Med, 2016, 375(15): 1448-1456.
46. 郭晓慧, 黄仟, 谢雁鸣, 等. 伞式设计与篮式设计在中医药循证评价中的应用. 中国中药杂志, 2021, 46(8): 2010-2015.
47. 张雯雯, 陈润生院士. 从新冠病毒、精准医学到核酸药物. 高科技与产业化, 2020, 10: 28-31.

Chinese Journal of Evidence-Based Medicine

Application of research methods of master protocol in precision medicine

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