The past few years have seen an increasing number of initiatives aimed at integrating information generated outside of confirmatory randomised clinical trials (RCTs) into drug development. However, data generated non-concurrently and through observational studies can provide results that are difficult to compare with randomised trial data. Moreover, the scientific questions these data can serve to answer often remain vague. Our starting point is to use clearly defined objectives for evidence generation, which are formulated towards early discussion with health technology assessment (HTA) bodies and are additional to regulatory requirements for authorisation of a new treatment. We propose FACTIVE (Flexible Augmented Clinical Trial for Improved eVidencE generation), a new class of study designs enabling flexible augmentation of confirmatory randomised controlled trials with concurrent and close-to-real-world elements. These enabling designs facilitate estimation of certain treatment effects in the confirmatory part and other, complementary treatment effects in a concurrent real-world part. Each stakeholder should use the evidence that is relevant within their own decision-making framework. High quality data are generated under one single protocol and the use of randomisation ensures rigorous statistical inference and interpretation within and between the different parts of the experiment. Evidence for the decision-making of HTA bodies could be available earlier than is currently the case.

翻译：过去几年中,越来越多的举措旨在将确认性随机临床试验之外产生的信息纳入药物开发;然而,目前和通过观察研究产生的非现成数据能够提供难以与随机试验数据进行比较的结果;此外,这些数据可以回答的科学问题往往仍然模糊不清;我们的出发点是利用明确界定的生成证据目标,即与卫生技术评估机构进行早期讨论,并将其作为批准新治疗的监管要求的补充;我们提议了 " 实用性 " (改进电子VidencE一代的灵活强化临床试验),这是一种新的研究设计,能够灵活地扩大与同时和接近现实的随机控制试验的确认性随机试验,这些设计有助于估计确认性试验部分的某些治疗效果,以及同时在现实世界部分的其他补充治疗效果;每个利益攸关方应使用与其自身决策框架相关的证据;根据一项单一议定书生成高质量数据,使用随机化确保严格的统计数据推断和解释,目前不同机构内和之间的试验阶段是证据。