Department of Economics and National Bureau of Economic Research, Massachusetts Institute of Technology, Cambridge, MA 02142.
Department of Economics and National Bureau of Economic Research, Brown University, Providence, RI 02912.
Proc Natl Acad Sci U S A. 2023 Dec 19;120(51):e2311556120. doi: 10.1073/pnas.2311556120. Epub 2023 Dec 15.
Pragmatic cancer screening trials mimic real-world scenarios in which patients and doctors are the ultimate arbiters of treatment. Intention-to-screen (ITS) analyses of such trials maintain randomization-based apples-to-apples comparisons, but differential adherence (the failure of subjects assigned to screening to get screened) makes ITS effects hard to compare across trials and sites. We show how instrumental variables (IV) methods address the nonadherence challenge in a comparison of estimates from 17 sites in five randomized trials measuring screening effects on colorectal cancer incidence. While adherence rates and ITS estimates vary widely across and within trials, IV estimates of per-protocol screening effects are remarkably consistent. An application of simple IV tools, including graphical analysis and formal statistical tests, shows how differential adherence explains variation in ITS impact. Screening compliers are also shown to have demographic characteristics similar to those of the full trial study sample. These findings argue for the clinical relevance of IV estimates of cancer screening effects.
实用癌症筛查试验模拟了实际情况下患者和医生是治疗的最终决策者的场景。对这些试验进行的意向性筛查（ITS）分析保留了基于随机分组的苹果对苹果的比较，但由于存在差异的依从性（被分配到筛查组的受试者未能接受筛查），使得 ITS 效果难以在不同试验和地点之间进行比较。我们展示了如何在比较五个随机试验中 17 个地点的估计值时，使用工具变量（IV）方法来解决非依从性挑战，这些试验测量了筛查对结直肠癌发病率的影响。虽然依从率和 ITS 估计值在试验之间和内部差异很大，但基于方案的筛查效果的 IV 估计值非常一致。简单 IV 工具的应用，包括图形分析和正式的统计检验，表明了差异的依从性如何解释 ITS 影响的变化。还表明，筛查顺从者具有与整个试验研究样本相似的人口统计学特征。这些发现证明了癌症筛查效果的 IV 估计值的临床相关性。
