Abstract：
The randomized controlled trial (RCT) forms the basis for drug approval by regulatory agencies. Observational studies using existing data from healthcare databases now also provide real-world evidence (RWE) in regulatory decision-making. Several initiatives are assessing the value of RWE by conducting observational studies that emulate published RCTs. While many RCTs are straightforward to emulate, others are challenging. We describe three RCT design aspects that pose challenges for observational studies. First are trials that enrol already treated subjects who must discontinue these treatments at the time of randomization, which can distort the comparison with observational studies. Second is the inclusion of a run-in phase, especially to exclude non-compliant subjects from the trial. Third are trials that evaluate the effect of weaning off treatment. In conclusion, future randomized trials that aim to be emulated by observational studies could consider study designs that allow emulation and thus provide valid and complementary RWE.
摘要：
随机对照试验（RCT）是监管机构批准药物的基础。使用医疗保健数据库中现有数据的观察性研究现在也为监管决策提供了现实世界的证据(RWE)。一些举措正在通过进行模拟已发表的RCT的观察性研究来评估RWE的价值。虽然许多RCT很容易模仿，其他人具有挑战性。我们描述了对观察性研究提出挑战的三个RCT设计方面。首先是注册已经接受治疗的受试者的试验，这些受试者必须在随机化时停止这些治疗，这可能会扭曲与观察性研究的比较。二是纳入磨合阶段,特别是将不合规的受试者排除在试验之外。第三是评估断奶治疗效果的试验。总之,未来旨在通过观察性研究进行模拟的随机试验可以考虑允许模拟的研究设计,从而提供有效和互补的RWE.
