Coalition for Epidemic Preparedness Innovations (CEPI), Oslo, Norway.
Clin Trials. 2021 Jun;18(3):286-294. doi: 10.1177/1740774520977283. Epub 2021 Mar 2.
Vaccines are potent tools to prevent outbreaks of emerging infectious diseases from becoming epidemics and need to be developed at an accelerated pace to have any impact on the course of an ongoing epidemic. The aim of this study was to describe time use in the execution of vaccine trials, to identify steps that could be accelerated to improve preparedness and planning for future emerging infectious diseases vaccine trials.
We used a mixed-methods approach to map time use and process steps that could be accelerated during vaccine trials. Trials for vaccines against infectious diseases registered in three global trial databases reported in the period 2011-2017 were eligible to join the survey. We invited sponsors to contribute data through a predefined structured questionnaire for clinical trial process metrics. Data were stratified by trial phase, disease type (i.e. emerging infectious diseases or not emerging infectious diseases), sponsor type, and continent. Qualitative interviews were conducted with purposively selected sponsors, and thematic analysis of the interview transcripts was performed.
Based on data from 155 vaccine trials including 29,071 subjects, 52% were phase I, 23% phase II, and 25% phase III. We found that the regulatory approval, subject enrollment, study execution, and study close-out accounted for most of the cycle time of the vaccine trial process. Cycle times for the regulatory and ethical approvals, contract agreement, site initiation, and study execution were shorter in trials conducted during outbreaks. Qualitative interviews indicated that early engagement of the regulatory and independent ethical committee authorities in planning the vaccine trials was critical for saving time in trial approval. Furthermore, adapting the trial implementation to the reality of the study sites and active involvement of the local investigators during the planning of the trial and protocol writing were stated to be of paramount importance to successful completion of trials at an accelerated pace.
The regulatory approval, subject recruitment, study execution, and close-out cycle times accounted for most of the vaccine trial time use and are activities that could be accelerated during a vaccine trial planning and implementation. We encourage tracking of key cycle time metrics and facilitating sharing of knowledge across industry and academia, as this may serve to reduce the time from index case detection to access of a vaccine during emerging infectious diseases epidemics.
疫苗是预防新发传染病爆发成为流行病的有力工具，需要加快速度开发，才能对正在进行的流行病的进程产生影响。本研究的目的是描述疫苗试验执行过程中的时间利用情况，确定可以加快的步骤，以提高对未来新发传染病疫苗试验的准备和规划。
我们采用混合方法来绘制时间利用图，并确定在疫苗试验中可以加快的步骤。符合条件的试验包括在 2011 年至 2017 年期间在三个全球试验数据库中注册的针对传染病的疫苗试验。我们邀请赞助商通过预先确定的临床试验过程指标结构化问卷提供数据。根据试验阶段、疾病类型（即新发传染病或非新发传染病）、赞助商类型和大陆，对数据进行分层。对有目的地选择的赞助商进行了定性访谈，并对访谈记录进行了主题分析。
基于包括 29071 名受试者在内的 155 项疫苗试验的数据，52%为 I 期，23%为 II 期，25%为 III 期。我们发现，监管批准、受试者招募、研究执行和研究结束占疫苗试验过程周期时间的大部分。在暴发期间进行的试验中，监管和伦理批准、合同协议、地点启动和研究执行的周期时间更短。定性访谈表明，在规划疫苗试验时，尽早让监管和独立伦理委员会当局参与，可以节省试验批准的时间。此外，在试验规划和方案撰写过程中，根据研究地点的实际情况调整试验实施，并积极参与当地研究人员的工作，被认为对加速完成试验至关重要。
监管批准、受试者招募、研究执行和关闭周期时间占疫苗试验时间利用的大部分，是在疫苗试验规划和实施过程中可以加快的活动。我们鼓励跟踪关键周期时间指标，并促进工业界和学术界之间的知识共享，因为这可能有助于减少从发现首例病例到获得新发传染病疫苗的时间。
