Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Clinical Epidemiology and Regenerative Medicine Programs, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.
Transfus Med Rev. 2020 Jul;34(3):165-171. doi: 10.1016/j.tmrv.2020.06.001. Epub 2020 Jun 27.
The urgent need for safe and effective treatments for COVID-19 has fueled the launch of many parallel complex studies of cellular therapies with small to modest enrolment projections. By pooling data from multiple studies that are similar, we can increase the ability to achieve sufficient power to determine effectiveness more quickly through meta-analysis. A scoping review of registered clinical trials using cell-based interventions for COVID-19 was conducted to identify candidate studies for meta-analysis that could support an accelerated regulatory review. ClinicalTrials.gov and WHO International Clinical Trials Registry Platform were searched April 23, 2020. Trials were included if they utilized cell or cell-derived products to treat or prevent COVID-19. Fifty-four registered cellular therapy trials were identified and included for analysis. Studies of mesenchymal stromal cells (MSCs; 41 studies; 1129 subjects projected to receive cells) and natural killer (NK) cells (5 studies; 135 projected to received cells) were observed most commonly. A subset of studies are controlled (34 studies, or 63%), including 27 studies of MSCs and 3 of NK cells. While heterogeneity in study design exists, the cumulative projected enrolment of patients from similar studies appears sufficient to allow the detection of meaningful differences in clinically important outcomes such as mortality, admission to intensive care and need for mechanical ventilation by September 2020-sooner than any individual study could determine effectiveness. MSCs are the predominant cell type in registered trials for severe or critical COVID-19 and represent the most promising candidates for future meta-analysis. Sufficient pooled sample size to detect clinically important reductions in multiple outcomes, including mortality, is anticipated by September 2020, but may require accessing supplementary data to align outcome reporting. Regulatory approval, funding and implementation by cell manufacturing partners will be accelerated by our framework for rapid meta-analysis.
迫切需要安全有效的 COVID-19 治疗方法，这促使许多细胞疗法的平行复杂研究迅速开展，这些研究的入组人数预计较少或适中。通过汇总多个类似研究的数据，我们可以通过荟萃分析提高快速确定疗效的能力。我们对基于细胞的 COVID-19 干预措施的注册临床试验进行了范围界定综述，以确定有资格进行荟萃分析的候选研究，这些研究可以支持加速监管审查。于 2020 年 4 月 23 日在 ClinicalTrials.gov 和世界卫生组织国际临床试验注册平台上进行了检索。如果试验使用细胞或细胞衍生产品来治疗或预防 COVID-19，则将其纳入。确定并纳入了 54 项注册的细胞治疗试验进行分析。观察到最常见的是间充质基质细胞（MSCs；41 项研究；预计有 1129 名受试者接受细胞治疗）和自然杀伤（NK）细胞（5 项研究；预计有 135 名受试者接受细胞治疗）的研究。一部分研究是对照研究（34 项研究，占 63%），包括 27 项 MSCs 研究和 3 项 NK 细胞研究。尽管研究设计存在异质性，但来自类似研究的累积预计入组患者人数足以允许在临床上重要的结局（如死亡率、入住重症监护病房和需要机械通气）方面检测到有意义的差异，这比任何单个研究都能确定疗效的时间要早。在严重或危急 COVID-19 的注册试验中，MSCs 是最主要的细胞类型，是未来荟萃分析最有前途的候选者。预计到 2020 年 9 月，将有足够的汇总样本量来检测多个结局（包括死亡率）的临床显著降低，但可能需要访问补充数据以对齐结局报告。通过我们的快速荟萃分析框架，细胞制造合作伙伴的监管批准、资金和实施将得到加速。
