Cuer Benjamin, Conroy Thierry, Juzyna Beata, Gourgou Sophie, Mollevi Caroline, Touraine Célia
Biometrics Unit, Montpellier Cancer Institute, 208, avenue des Apothicaires, 34298, Montpellier, France.
French National Platform Quality of Life and Cancer, Montpellier, France.
Qual Life Res. 2022 May;31(5):1359-1370. doi: 10.1007/s11136-021-03040-8. Epub 2021 Nov 24.
Health-related quality of life (HRQoL) is an important endpoint in cancer clinical trials. Analysis of HRQoL longitudinal data is plagued by missing data, notably due to dropout. Joint models are increasingly receiving attention for modelling longitudinal outcomes and the time-to-dropout. However, dropout can be informative or non-informative depending on the cause.
We propose using a joint model that includes a competing risks sub-model for the cause-specific time-to-dropout. We compared a competing risks joint model (CR JM) that distinguishes between two causes of dropout with a standard joint model (SJM) that treats all the dropouts equally. First, we applied the CR JM and SJM to data from 267 patients with advanced oesophageal cancer from the randomized clinical trial PRODIGE 5/ACCORD 17 to analyse HRQoL data in the presence of dropouts unrelated and related to a clinical event. Then, we compared the models using a simulation study.
We showed that the CR JM performed as well as the SJM in situations where the risk of dropout was the same whatever the cause. In the presence of both informative and non-informative dropouts, only the SJM estimations were biased, impacting the HRQoL estimated parameters.
The systematic collection of the reasons for dropout in clinical trials would facilitate the use of CR JMs, which could be a satisfactory approach to analysing HRQoL data in presence of both informative and non-informative dropout.
This study is registered with ClinicalTrials.gov, number NCT00861094.
与健康相关的生活质量（HRQoL）是癌症临床试验中的一个重要终点。HRQoL纵向数据的分析受到缺失数据的困扰，尤其是由于失访造成的。联合模型在对纵向结果和失访时间进行建模方面越来越受到关注。然而，根据原因不同，失访可能是信息性的或非信息性的。
我们建议使用一种联合模型，该模型包括一个针对特定原因失访时间的竞争风险子模型。我们将区分两种失访原因的竞争风险联合模型（CR JM）与将所有失访同等对待的标准联合模型（SJM）进行了比较。首先，我们将CR JM和SJM应用于来自随机临床试验PRODIGE 5/ACCORD 17的267例晚期食管癌患者的数据，以分析存在与临床事件无关和相关的失访情况下的HRQoL数据。然后，我们通过模拟研究对模型进行了比较。
我们表明，在无论何种原因失访风险相同的情况下，CR JM的表现与SJM一样好。在同时存在信息性和非信息性失访的情况下，只有SJM的估计存在偏差，影响了HRQoL估计参数。
在临床试验中系统收集失访原因将有助于CR JM的使用，这可能是一种在存在信息性和非信息性失访情况下分析HRQoL数据的令人满意的方法。
本研究已在ClinicalTrials.gov注册，编号为NCT00861094。
