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：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

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

1.	趙曉宇, 刁天喜, 高云華, 等. 美國“精準醫學計劃”解讀與思考. 軍事醫學, 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.	吳家睿. 精確醫學5年歷程的回顧與思考(上). 醫學與哲學, 2021, 42(20): 1-4,10.
6.	關之玥, 劉巖, 張晶晶, 等. 母方案平臺試驗設計方法及其在相關領域中的應用. 中國循證醫學雜志, 2021, 21(8): 986-992.
7.	毛元銘, 詹瑨祺, 王榕榕, 等. 臨床醫學試驗主方案概述及其應用. 中國新藥雜志, 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.	國家藥品監督管理局藥品審評中心. 藥物臨床試驗適應性設計指導原則(試行).
14.	國家藥品監督管理局藥品審評中心. 抗腫瘤藥物臨床試驗統計學設計指導原則(試行).
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, J?nne 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, 蘇麗文, 袁鷹, 等. 抗腫瘤藥物主方案試驗設計進展及統計考量. 中國衛生統計, 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.	于亞南, 杜培艷, 劉駿, 等. 精準醫學創新性臨床試驗設計"主方案"研究的概念、設計與案例. 中國新藥雜志, 2020, 29(23): 2712-2717.
38.	錢真真, 周莎, 于亞南, 等. 適應性隨機化及其在臨床試驗中的應用操作要點. 中國循證醫學雜志, 2022, 22(8): 971-977.
39.	衡明莉, 王北琪, 王駿. 對美國FDA適應性設計指導原則的介紹. 中國臨床藥理學雜志, 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.	郭曉慧, 黃仟, 謝雁鳴, 等. 傘式設計與籃式設計在中醫藥循證評價中的應用. 中國中藥雜志, 2021, 46(8): 2010-2015.
47.	張雯雯, 陳潤生院士. 從新冠病毒、精準醫學到核酸藥物. 高科技與產業化, 2020, 10: 28-31.

1. 趙曉宇, 刁天喜, 高云華, 等. 美國“精準醫學計劃”解讀與思考. 軍事醫學, 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. 吳家睿. 精確醫學5年歷程的回顧與思考(上). 醫學與哲學, 2021, 42(20): 1-4,10.
6. 關之玥, 劉巖, 張晶晶, 等. 母方案平臺試驗設計方法及其在相關領域中的應用. 中國循證醫學雜志, 2021, 21(8): 986-992.
7. 毛元銘, 詹瑨祺, 王榕榕, 等. 臨床醫學試驗主方案概述及其應用. 中國新藥雜志, 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. 國家藥品監督管理局藥品審評中心. 藥物臨床試驗適應性設計指導原則(試行).
14. 國家藥品監督管理局藥品審評中心. 抗腫瘤藥物臨床試驗統計學設計指導原則(試行).
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, J?nne 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, 蘇麗文, 袁鷹, 等. 抗腫瘤藥物主方案試驗設計進展及統計考量. 中國衛生統計, 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. 于亞南, 杜培艷, 劉駿, 等. 精準醫學創新性臨床試驗設計"主方案"研究的概念、設計與案例. 中國新藥雜志, 2020, 29(23): 2712-2717.
38. 錢真真, 周莎, 于亞南, 等. 適應性隨機化及其在臨床試驗中的應用操作要點. 中國循證醫學雜志, 2022, 22(8): 971-977.
39. 衡明莉, 王北琪, 王駿. 對美國FDA適應性設計指導原則的介紹. 中國臨床藥理學雜志, 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. 郭曉慧, 黃仟, 謝雁鳴, 等. 傘式設計與籃式設計在中醫藥循證評價中的應用. 中國中藥雜志, 2021, 46(8): 2010-2015.
47. 張雯雯, 陳潤生院士. 從新冠病毒、精準醫學到核酸藥物. 高科技與產業化, 2020, 10: 28-31.

Chinese Journal of Evidence-Based Medicine

Application of research methods of master protocol in precision medicine

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content