Katayama Miyuki, Shikano Mayumi
Graduate School of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan.
Front Med (Lausanne). 2025 Apr 15;12:1482035. doi: 10.3389/fmed.2025.1482035. eCollection 2025.
The clinical development of therapeutics for COVID-19 proceeded at an extraordinary pace. Given the lack of studies evaluating this experience systematically, we analyzed the clinical development methods for COVID-19 therapeutics to determine strategies for shortening the clinical development period in preparation for future pandemics.
We confirmed the US-FDA review documents for fourteen products that underwent Emergency Use Authorization (EUA) in the US during the COVID-19 pandemic to examine the time required for clinical development and regulatory review and the submitted data for EUA.
Six of the fourteen products with clinical study data for other indications were evaluated in fewer studies than new molecular entities. The application data for each product included the stipulated content, and placebo-controlled comparative studies were included for all products. Clinical development measures were adopted, including adaptive protocol design, nonsequential phase development, and clinical dose adaptation based on non-clinical study results.
Products with clinical study data for other indications are advantageous for early approval. However, early approval of new molecular entities is also important because they may not be sufficiently effective against new infectious diseases. It would be effective to approve a product promptly for a limited target population at first and then gradually expand it as data becomes more abundant. To prepare for future pandemics, we recommend establishing a framework for identifying candidates from existing products, managing and disseminating information in emergencies at various levels, and clarifying the conditions for applying regulatory flexibility to encourage pharmaceutical companies to make early decisions regarding clinical development.
用于治疗新型冠状病毒肺炎（COVID-19）的疗法临床研发进展异常迅速。鉴于缺乏系统性评估这一历程的研究，我们分析了COVID-19疗法的临床研发方法，以确定缩短临床研发周期的策略，为未来大流行做准备。
我们确认了美国食品药品监督管理局（US-FDA）对14种在COVID-19大流行期间于美国获得紧急使用授权（EUA）的产品的审评文件，以审查临床研发和监管审评所需时间以及提交的EUA数据。
14种具有其他适应症临床研究数据的产品中，有6种产品所开展的研究少于新分子实体。每种产品的申报数据均包含规定内容，且所有产品均纳入了安慰剂对照比较研究。采取了临床研发措施，包括适应性方案设计、非序贯阶段研发以及基于非临床研究结果进行临床剂量调整。
具有其他适应症临床研究数据的产品有利于早期获批。然而，新分子实体的早期获批也很重要，因为它们可能对新发传染病的疗效欠佳。首先针对有限的目标人群迅速批准产品，然后随着数据增多逐步扩大适用人群，这将是有效的做法。为应对未来大流行，我们建议建立一个框架，用于从现有产品中识别候选产品、在各级紧急情况下管理和传播信息，以及明确应用监管灵活性的条件，以鼓励制药公司就临床研发尽早做出决策。
