论文标题
疾病发病率登记册的试验仿真和生存分析:关于先前肾脏移植的因果效应的案例研究
Trial emulation and survival analysis for disease incidence registers: a case study on the causal effect of pre-emptive kidney transplantation
论文作者
论文摘要
许多教程和研究论文重点介绍了生存分析或因果推断中的方法,在医学研究中的常见并发症未经应对。实际上,必须共同处理问题,而不会忽略数据结构的基本特征的奢侈。在本文中,我们遵循终末期肾脏疾病的事件病例,并检查对以移植,所谓的预先避免的肾脏移植和透析的方式开始治疗的全因死亡率。这个问题相对简单:预计哪种治疗开始将为目标人群带来最佳生存?为了解决这个问题,我们模仿了有关瑞典肾脏注册中心的目标试验,以估计对生存曲线的因果影响。意识到重要的挑战,我们看到了以前的研究如何根据发生后治疗开始的事件选择患者进入治疗组。我们的研究揭示了导致不变的时间偏见和长期入射疾病登记处的其他典型特征的巨大影响,包括:在登记册的(早期)阶段(早期)阶段(早期)阶段缺失或不匹配的协变量,在这几年中,患者在日历时间内进入治疗组的风险变化和风险的变化会改善多年的护理。随着病例和版本的特征随着时间的流逝而发展,未经调整的Kaplan-Meier曲线中引入了信息审查,其IPW版本也不再有效。在这里,我们讨论了处理这些功能的可行方法,并回答了不同的研究问题,以依赖于未衡量的基线混杂因素的假设。
Numerous tutorials and research papers focus on methods in either survival analysis or causal inference, leaving common complications in medical studies unaddressed. In practice one must handle problems jointly, without the luxury of ignoring essential features of the data structure. In this paper, we follow incident cases of end-stage renal disease and examine the effect on all-cause mortality of starting treatment with transplant, so-called pre-emptive kidney transplantation, versus dialysis. The question is relatively simple: which treatment start is expected to bring the best survival for a target population? To address the question, we emulate a target trial drawing on the Swedish Renal Registry to estimate a causal effect on survival curves. Aware of important challenges, we see how previous studies have selected patients into treatment groups based on events occurring post treatment initiation. Our study reveals the dramatic impact of resulting immortal time bias and other typical features of long term incident disease registries, including: missing or mismeasured covariates during (the early) phases of the register, varying risk profile of patients entering treatment groups over calendar time and changes in risk as care improves over the years. With characteristics of cases and versions of treatment evolving over time, informative censoring is introduced in unadjusted Kaplan-Meier curves and also their IPW version is no longer valid. Here we discuss feasible ways of handling these features and answer different research questions relying on the no unmeasured baseline confounders assumption.