Adaptive Design Randomized Controlled Clinical Trials

doi:10.3969/j.issn.1673-5765.2022.10.019

Abstract

Abstract: In recent years, adaptive design has been widely used in clinical trials due to its flexibility and efficiency. In practice, adaptive design can give researchers a second chance to adjust the trial design during the study. This article briefly introduced historical origins, basic concepts, design types, design characteristics, case analysis, statistical methods, and reporting standards of adaptive design.

Key words: Adaptive design; Clinical trial; Group sequential trial; Randomized controlled trial

摘要： 近年来，适应性设计因其灵活性和高效率而在临床试验中得到了广泛的应用。在实践中，适应性设计可以为研究者提供第二次机会，在研究进行中调整试验设计。本文将重点从历史渊源、基本概念、设计类型、设计特点、案例解读、统计分析及报告规范等方面对适应性设计进行简要介绍。

关键词: 适应性设计; 临床试验; 成组序贯试验; 随机对照

YANG Kaixuan, ZHOU Qi, JIANG Yingyu, GU Hongqiu. Adaptive Design Randomized Controlled Clinical Trials [J]. Chinese Journal of Stroke, 2022, 17(10): 1152-1158.

杨凯璇, 周齐, 姜英玉, 谷鸿秋. 适应性设计随机对照临床试验[J]. 中国卒中杂志, 2022, 17(10): 1152-1158.

References

1] PALLMANN P，BEDDING A W，CHOODARI-OSKOOEI B，et al. Adaptive designs in clinical trials：why use them，and how to run and report them[J]. BMC Med，2018，16（1）：29.
[2] BHATT D L，MEHTA C. Adaptive designs for clinical trials[J]. N Engl J Med，2016，375（1）：65-74.
[3] Food and Drug Administration. Challenge and opportunity on the critical path to new medical products[EB/OL].（2018-01-25）[2022-08-10]. http://wayback.archive-it.org/7993/20180125035500/https://www. fda. gov/downloads/ScienceResearch/SpecialTopics/CriticalPathInitiative/CriticalPathOpportunitiesReports/UCM113411. pdf.
[4] COLLIGNON O，KOENIG F，KOCH A，et al. Adaptive designs in clinical trials：from scientific advice to marketing authorisation to the European medicine agency[J]. Trials，2018，19（1）：642.
[5] Food and Drug Administration. Draft guidance for industry-adaptive design clinical trials for drugs and biologics[EB/OL].（2010-02-26）[2022-08-10]. https://www.federalregister.gov/documents/2010/02/26/2010-3980/draft-guidance-for-industry-on-adaptive-design-clinical-trials-for-drugs-and-biologics-availability#:~:text=FDA%20is%20announcing%20the%20availability%20of%20a%20draft,design%20trials%20when%20used%20in%20drug%20development%20programs.
[6] Food and Drug Administration. Adaptive designs for clinical trials of drugs and biologics guidance for industry[EB/OL].（2019-11-29）[2022-08-10]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry.
[7] Food and Drug Administration. Adaptive designs for medical device clinical studies[EB/OL].（2018-10-01）[2022-08-10]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-designs-medical-device-clinical-studies.
[8] 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）[EB/OL].（2021-01-29）[2022-08-10]. https://www.cde.org.cn/zdyz/domesticinfopage?zdyzIdCODE=4409e51a403a911757af6caf3ecef129.
[9] CHOW S C，CHANG M，PONG A. Statistical consideration of adaptive methods in clinical development[J]. J Biopharm Stat，2005，15（4）：575-591.
[10] GALLO P，CHUANG-STEIN C，DRAGALIN V，et al. Adaptive designs in clinical drug development--an executive summary of the PhRMA working group[J]. J Biopharm Stat，2006，16（3）：275-283.
[11] CHOW S C. Adaptive clinical trial design[J/OL]. Annu Rev Med，2014，65：405-415[2022-08-10]. https://doi.org/10.1146/annurev-med-092012-112310.
[12] 陈峰，夏结来. 临床试验统计学[M]. 北京：人民卫生出版社，2018.
[13] WANG S J，HUNG H M，O'NEILL R. Paradigms for adaptive statistical information designs：practical experiences and strategies[J]. Stat Med，2012，31（25）：3011-3023.
[14] LAI T L，LAVORI P W，TSANG K W. Adaptive design of confirmatory trials：advances and challenges[J/OL]. Contemp Clin Trials，2015，45（Pt A）：93-102[2022-08-10]. https://doi.org/10.1016/j. cct.2015.06.007.
[15] LAI T L，LAVORI P W，SHIH M C. Adaptive trial designs[J/OL]. Annu Rev Pharmacol Toxicol，2012，52：101-110[2022-08-10]. https://doi.org/10.1146/annurev-pharmtox-010611-134504.
[16] BURNETT T，MOZGUNOV P，PALLMANN P，et al. Adding flexibility to clinical trial designs：an example-based guide to the practical use of adaptive designs[J]. BMC Med，2020，18（1）：352.
[17] KOJIMA M. Adaptive design for identifying maximum tolerated dose early to accelerate dose-finding trial[J]. BMC Med Res Methodol，2022，22（1）：97.
[18] LYU J，CURRAN E，JI Y. Bayesian adaptive design for finding the maximum tolerated sequence of doses in multicycle dose-finding clinical trials[J/OL]. JCO Precis Oncol，2018，2：1-19[2022-08-10]. https://doi. org/10.1200/PO.18.00020.
[19] ORON A P，SOUTER M J，FLOURNOY N. Understanding research methods：up-and-down designs for dose-finding[J]. Anesthesiology，2022，137（2）：137-150.
[20] ALMASRI S，ZENATI M，HAMMAD A，et al. Adaptive dynamic therapy and survivorship for operable pancreatic cancer[J/OL]. JAMA Netw Open，2022，5（6）：e2218355[2022-08-10]. https://doi. org/10.1001/jamanetworkopen.2022.18355.
[21] CERQUEIRA F P，JESUS A M C，COTRIM M D. Adaptive design：a review of the technical，statistical，and regulatory aspects of implementation in a clinical trial[J]. Ther Innov Regul Sci，2020，54（1）：246-258.
[22] KAIRALLA J A，COFFEY C S，THOMANN M A，et al. Adaptive trial designs：a review of barriers and opportunities[J/OL]. Trials，2012，13：145[2022-08-10]. https://doi.org/10.1186/1745-6215-13-145.
[23] CHOW S C，CHANG M. Adaptive design methods in clinical trials-a review[J/OL]. Orphanet J Rare Dis，2008，3：11[2022-08-10]. https://doi.org/10. 1186/1750-1172-3-11.
[24] HILL M D，GOYAL M，MENON B K，et al. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke（ESCAPE-NA1）：a multicentre，double-blind，randomised controlled trial[J]. Lancet，2020，395（10227）：878-887.
[25] SWANSON C J，ZHANG Y，DHADDA S，et al. A randomized，double-blind，phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab，an anti-Aβ protofibril antibody[J]. Alzheimers Res Ther，2021，13（1）：80.
[26] JONES A E，PUSKARICH M A，SHAPIRO N I，et al. Effect of levocarnitine vs placebo as an adjunctive treatment for septic shock：the rapid administration of carnitine in sepsis（RACE）randomized clinical trial[J/OL]. JAMA Netw Open，2018，1（8）：e186076[2022-08-10]. https://doi.org/10.1001/jamanetworkopen.2018.6076.
[27] JOHNSTON S C，AMARENCO P，ALBERS G W，et al. Ticagrelor versus aspirin in acute stroke or transient ischemic attack[J]. N Engl J Med，2016，375（1）：35-43.
[28] JOHNSTON S C，AMARENCO P，DENISON H，et al. Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA[J]. N Engl J Med，2020，383（3）：207-217.
[29] THORLUND K，HAGGSTROM J，PARK J J，et al. Key design considerations for adaptive clinical trials：a primer for clinicians[J/OL]. BMJ，2018，360：k698[2022-08-10]. https://doi.org/10.1136/bmj.k698.
[30] GRAYLING M J，WHEELER G M. A review of available software for adaptive clinical trial design[J]. Clinical Trials，2020，17（3）：323-331.
[31] DIMAIRO M，PALLMANN P，WASON J，et al. The adaptive designs CONSORT extension（ACE）statement：a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design[J/OL]. BMJ，2020，369：m115[2022-08-10]. https://doi.org/10.1136/bmj.m115.

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[9]	XIE Li-Hua;HOU Jing-Tian;HOU Yu-Li.. Urinary Kallid Therapy for Acute Cerebral Infarction: A Meta Analysis [J]. , 2011, 6(04): 287-296.