The Landscape of COVID-19 Research in the United States: a Cross-sectional Study of Randomized Trials Registered on ClinicalTrials.Gov.
The Landscape of COVID-19 Research in the United States: a Cross-sectional Study of Randomized Trials Registered on ClinicalTrials.Gov.
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DOI：
10.1007/s11606-021-07167-9
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发表时间：
2022-01
影响因子：
5.7
通讯作者：
Fralick M
中科院分区：
文献类型：
--
作者：
Sacks CA;North CM;Wolf M;Dougan M;Campbell KR;Moggridge J;Fralick M
SARS-CoV-2已感染全球2亿多人，导致400多万人死亡。随机对照试验是确定针对这种新型病原体的有效治疗方法的最佳工具。描述美国在疫情爆发前9个月开展的COVID-19治疗随机对照试验的特征。设计、设置和参与者我们对截至2020年8月10日在www.clinicaltrials.gov上注册的所有已完成或正在积极招募的治疗COVID-19的随机、干预性临床试验进行了一项横断面研究。我们排除了旨在预防COVID-19的疫苗和其他干预措施的试验。主要结果和测量我们使用描述性统计来描述临床试验和现有研究的统计功效。对于后期试验（即，3期和2/3期研究），我们将临床试验的地理分布与诊断出患有COVID-19的人的地理分布进行了比较。我们确定了200项关于COVID-19患者治疗的随机对照试验。在所有试验中，87项（43.5%）为单中心试验，64项（32.0%）为揭盲试验，80项（40.0%）由行业申办。最常见的治疗包括单克隆抗体（N=46项试验）、小分子免疫调节剂（N=28）、抗病毒药物（N=24项试验）和羟氯喹（N=20项试验）。截至2020年8月完成的9项试验中，中位样本量为450（IQR 67-1113）; 191项正在进行的试验中，中位计划样本量为150（IQR 60-400）。在晚期试验（N=54）中，最常见的主要结局是严重程度量表（N=23，42.6%），其次是死亡和通气的复合终点（N=10，18.5%）和单独死亡（N=6，11.1%）。在这些后期试验中，所有抗病毒药物、单克隆抗体或氯喹/羟氯喹的试验检测死亡率相对风险降低20%的能力均低于25%。如果针对某一特定治疗类别的单独试验形成单一试验，则检测到相同死亡率降低的功效将大于98%。在获得试验方面存在很大的差异，东北部的人均试验次数最多，中西部最少。在疫情初期开展了大量随机试验，以评估COVID-19的治疗方法。然而，许多试验在重要临床终点方面的效力不足，并且观察到了巨大的地理差异，这突出了改善国家临床试验基础设施的重要性。在线版本包含补充材料，可通过10.1007/s11606-021-07167-9获得。
SARS-CoV-2 has infected over 200 million people worldwide, resulting in more than 4 million deaths. Randomized controlled trials are the single best tool to identify effective treatments against this novel pathogen. To describe the characteristics of randomized controlled trials of treatments for COVID-19 in the United States launched in the first 9 months of the pandemic. Design, Setting, and Participants We conducted a cross-sectional study of all completed or actively enrolling randomized, interventional, clinical trials for the treatment of COVID-19 in the United States registered on www.clinicaltrials.gov as of August 10, 2020. We excluded trials of vaccines and other interventions intended to prevent COVID-19. Main Outcomes and Measures We used descriptive statistics to characterize the clinical trials and the statistical power for the available studies. For the late-phase trials (i.e., phase 3 and 2/3 studies), we compared the geographic distribution of the clinical trials with the geographic distribution of people diagnosed with COVID-19. We identified 200 randomized controlled trials of treatments for people with COVID-19. Across all trials, 87 (43.5%) were single-center, 64 (32.0%) were unblinded, and 80 (40.0%) were sponsored by industry. The most common treatments included monoclonal antibodies (N=46 trials), small molecule immunomodulators (N=28), antiviral medications (N=24 trials), and hydroxychloroquine (N=20 trials). Of the 9 trials completed by August 2020, the median sample size was 450 (IQR 67–1113); of the 191 ongoing trials, the median planned sample size was 150 (IQR 60–400). Of the late-phase trials (N=54), the most common primary outcome was a severity scale (N=23, 42.6%), followed by a composite of mortality and ventilation (N=10, 18.5%), and mortality alone (N=6, 11.1%). Among these late-phase trials, all trials of antivirals, monoclonal antibodies, or chloroquine/hydroxychloroquine had a power of less than 25% to detect a 20% relative risk reduction in mortality. Had the individual trials for a given class of treatments instead formed a single trial, the power to detect that same reduction in mortality would have been greater than 98%. There was large variability in access to trials with the highest number of trials per capita in the Northeast and the lowest in the Midwest. A large number of randomized trials were launched early in the pandemic to evaluate treatments for COVID-19. However, many trials were underpowered for important clinical endpoints and substantial geographic disparities were observed, highlighting the importance of improving national clinical trial infrastructure. The online version contains supplementary material available at 10.1007/s11606-021-07167-9.
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DOI：
10.3390/life10120350
发表时间：
2020-12-15
期刊：
Life (Basel, Switzerland)
影响因子：
--
作者：
Mathioudakis AG;Fally M;Hashad R;Kouta A;Hadi AS;Knight SB;Bakerly ND;Singh D;Williamson PR;Felton T;Vestbo J
通讯作者：
Vestbo J
DOI：
10.1177/17407745211049829
发表时间：
2022-03
期刊：
Clinical trials (London, England)
影响因子：
--
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
通讯作者：
Lundgren JD
影响因子：
3.2
作者：
Blehar, Mary C.;Spong, Catherine;Clayton, Janine A.
通讯作者：
Clayton, Janine A.
影响因子：
120.7
作者：
Sterne, Jonathan A. C.;Murthy, Srinivas;Marshall, John C.
通讯作者：
Marshall, John C.
影响因子：
158.5
作者：
Beigel, John H.;Tomashek, Kay M.;Lane, H. Clifford
通讯作者：
Lane, H. Clifford