Target trial emulation has improved comparative effectiveness research by making the causal question, assumptions, and analysis plan explicit. However, target trial protocols are usually developed iteratively. After examining the data, investigators revise the protocol to reflect which target trials the observational data can realistically support. While this iterative procedure is part of normal scientific practice, it raises concerns about selective choices and invalid statistical inference. A simple procedure can address these concerns. This procedure is based on sample splitting. In the initial split, investigators explore the data to define a target trial protocol. When these choices are made, the target trial protocol is implemented on the second split. Although the investigators made data-informed choices to select the target trial protocol, the inference has the usual coverage guarantees. The procedure is created to mirror how trialists move from pilot studies to a phase 3 trial. First, they use data from pilots and early-phase trials to learn and decide on a final protocol. Then they implement this protocol and analyze a new set of data in a phase 3 trial.

翻译：靶向试验模拟通过明确因果问题、假设和分析方案，改善了比较效果研究。然而，靶向试验方案通常经过反复迭代开发。研究者在检查数据后，会修订方案以反映观察性数据实际能够支持的靶向试验类型。尽管这种迭代过程属于常规科学实践的一部分，但它引发了关于选择性选择与无效统计推断的担忧。一个简单的程序可以解决这些问题。该程序基于样本分割。在初始分割中，研究者探索数据以定义靶向试验方案。当这些选择确定后，该靶向试验方案将在第二次分割中实施。尽管研究者基于数据信息选择了靶向试验方案，但推断仍具有通常的覆盖保证。该程序的设计旨在模拟试验者如何从预试验过渡到III期试验：首先，他们利用预试验和早期试验的数据进行学习并确定最终方案；随后，在III期试验中实施该方案并分析新数据集。