Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).
Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3).
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DOI：
10.1177/17407745211049829
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Lundgren JD
中科院分区：
文献类型：
--
作者：
Murray DD;Babiker AG;Baker JV;Barkauskas CE;Brown SM;Chang CC;Davey VJ;Gelijns AC;Ginde AA;Grund B;Higgs E;Hudson F;Kan VL;Lane HC;Murray TA;Paredes R;Parmar MK;Pett S;Phillips AN;Polizzotto MN;Reilly C;Sandkovsky U;Sharma S;Teitelbaum M;Thompson BT;Young BE;Neaton JD;Lundgren JD
迫切需要安全有效的COVID-19疗法。为了满足这一需求，加速COVID-19治疗干预和疫苗公私合作伙伴关系发起了COVID-19住院患者治疗（TICO）。TICO是一个多组、多阶段的平台主方案，有助于快速评估新型候选抗病毒治疗药物对因COVID-19住院的成人的安全性和疗效。到目前为止，已有五名特工加入了议定书，其中三名特工已经得到了快速答复。预计2021年全年将有其他药剂进入方案。该协议包含了一些关键的设计和实现功能，沿着的协议团队所面临的挑战，提出和讨论。三个临床试验网络，包括一个全球临床研究中心网络，参与了方案的制定和实施。TICO采用多组、多阶段设计，在入组的300例患者中采用灵活和稳健的方法进行无效性和安全性评价，如果药物显示出可接受的安全性特征和有效性证据，则随后扩展至全样本量和扩展的目标人群。通过共享安慰剂、将药物特异性信息限制在方案附录和模块化同意书中，可以快速招募多种药物。与美国食品药品监督管理局合作，制定了全面的安全性数据收集和DSMB时间表，用于研究在COVID-19住院患者中具有有限人体数据的潜在治疗药物。截至2021年8月8日，已有5种药物进入TICO主方案，共有1909名受试者被随机分配至其中一种药物或匹配的安慰剂。研究团队面临着许多挑战，需要克服这些挑战才能在全球研究中心网络中成功实施TICO。其中包括确保药物供应和可靠的招募，允许在全球研究中心网络中改变感染率，需要在不给临床工作人员带来过重负担的情况下平衡数据和样本的收集，以及在全球研究中心网络中获得监管批准。通过强大的多网络合作伙伴关系，TICO协议已成功用于全球研究中心网络，用于快速生成多种新型抗病毒药物的疗效数据。该协议中使用的协议设计和实现功能以及应对挑战的方法将具有更广泛的适用性。需要建立机制，促进各国监管机构之间更好的沟通和协调，以充分发挥这一方法在应对全球疫情方面的潜力。
Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public-private partnership initiated the Therapeutics for Inpatients with COVID-19 (TICO). TICO is a multi-arm, multi-stage platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate antiviral therapeutic agents for adults hospitalized with COVID-19. Five agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed. Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. TICO utilizes a multi-arm, multi-stage design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full sample size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo, the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and DSMB schedule was developed for the study of potential therapeutic agents with limited in-human data in hospitalized patients with COVID-19. As of August 08th 2021, five agents have entered the TICO master protocol and a total of 1909 participants have been randomized to one of these agents or matching placebo. There were a number of challenges faced by the study team that needed to be overcome in order to successfully implement TICO across a global network of sites. These included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and samples without overburdening clinical staff and obtaining regulatory approvals across a global network of sites. Through a robust multi-network partnership, the TICO protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required to achieve the full potential of this approach in dealing with a global outbreak.
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影响因子：
2
作者：
Royston, P;Parmar, MKB;Qian, W
通讯作者：
Qian, W
影响因子：
33.9
作者：
Chow, Nancy;Fleming-Dutra, Katherine;Ussery, Emily
通讯作者：
Ussery, Emily
影响因子：
158.5
作者：
Beigel, John H.;Tomashek, Kay M.;Lane, H. Clifford
通讯作者：
Lane, H. Clifford
DOI：
10.1177/1740774520939938
发表时间：
2020-10
期刊：
Clinical trials (London, England)
影响因子：
--
作者：
Dodd LE;Follmann D;Wang J;Koenig F;Korn LL;Schoergenhofer C;Proschan M;Hunsberger S;Bonnett T;Makowski M;Belhadi D;Wang Y;Cao B;Mentre F;Jaki T
通讯作者：
Jaki T
影响因子：
13.2
作者：
Leung TYM;Chan AYL;Chan EW;Chan VKY;Chui CSL;Cowling BJ;Gao L;Ge MQ;Hung IFN;Ip MSM;Ip P;Lau KK;Lau CS;Lau LKW;Leung WK;Li X;Luo H;Man KKC;Ng VWS;Siu CW;Wan EYF;Wing YK;Wong CSM;Wong KHT;Wong ICK
通讯作者：
Wong ICK