Health Services Research Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO), Valencia, Spain.
Department of Statistics and Operations Research. Universitat de València, Valencia, Spain.
BMC Med Res Methodol. 2023 Feb 14;23(1):40. doi: 10.1186/s12874-023-01859-y.
Multi-state models are complex stochastic models which focus on pathways defined by the temporal and sequential occurrence of numerous events of interest. In particular, the so-called illness-death models are especially useful for studying probabilities associated to diseases whose occurrence competes with other possible diseases, health conditions or death. They can be seen as a generalization of the competing risks models, which are widely used to estimate disease-incidences among populations with a high risk of death, such as elderly or cancer patients. The main advantage of the aforementioned illness-death models is that they allow the treatment of scenarios with non-terminal competing events that may occur sequentially, which competing risks models fail to do.
We propose an illness-death model using Cox proportional hazards models with Weibull baseline hazard functions, and applied the model to a study of recurrent hip fracture. Data came from the PREV2FO cohort and included 34491 patients aged 65 years and older who were discharged alive after a hospitalization due to an osteoporotic hip fracture between 2008-2015. We used a Bayesian approach to approximate the posterior distribution of each parameter of the model, and thus cumulative incidences and transition probabilities. We also compared these results with a competing risks specification.
Posterior transition probabilities showed higher probabilities of death for men and increasing with age. Women were more likely to refracture as well as less likely to die after it. Free-event time was shown to reduce the probability of death. Estimations from the illness-death and the competing risks models were identical for those common transitions although the illness-death model provided additional information from the transition from refracture to death.
We illustrated how multi-state models, in particular illness-death models, may be especially useful when dealing with survival scenarios which include multiple events, with competing diseases or when death is an unavoidable event to consider. Illness-death models via transition probabilities provide additional information of transitions from non-terminal health conditions to absorbing states such as death, what implies a deeper understanding of the real-world problem involved compared to competing risks models.
多状态模型是一种复杂的随机模型,其重点是通过大量感兴趣事件的时间和顺序发生来定义途径。特别是所谓的发病-死亡模型对于研究与其他可能的疾病、健康状况或死亡竞争的疾病发生的概率特别有用。它们可以被视为竞争风险模型的推广,竞争风险模型广泛用于估计具有高死亡风险的人群中的疾病发病率,例如老年人或癌症患者。上述发病-死亡模型的主要优点是,它们允许处理可能顺序发生的非终末期竞争事件的情况,而竞争风险模型无法做到这一点。
我们提出了一种使用具有 Weibull 基线风险函数的 Cox 比例风险模型的发病-死亡模型,并将该模型应用于复发性髋部骨折的研究。数据来自 PREV2FO 队列,包括 34491 名年龄在 65 岁及以上的患者,他们在 2008-2015 年期间因骨质疏松性髋部骨折住院治疗后存活出院。我们使用贝叶斯方法来近似模型每个参数的后验分布,从而得到累积发生率和转移概率。我们还将这些结果与竞争风险规范进行了比较。
后验转移概率显示男性死亡的概率更高,并且随着年龄的增长而增加。女性更容易再次骨折,而且在骨折后死亡的可能性较小。无事件时间显示出降低死亡概率的作用。尽管发病-死亡模型提供了从再次骨折到死亡的过渡的额外信息,但在常见过渡方面,发病-死亡和竞争风险模型的估计结果是相同的。
我们说明了多状态模型,特别是发病-死亡模型,在处理包括多种事件、竞争疾病或死亡是必须考虑的不可避免事件的生存情况时,可能特别有用。通过转移概率的发病-死亡模型提供了从非终末期健康状况到吸收状态(如死亡)的转移的额外信息,这与竞争风险模型相比,意味着对实际问题的理解更加深入。