Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusion
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. Trial registration: This study is registered with ClinicalTrials.gov, number NCT00861094.
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Acknowledgements
The authors thank the study sponsor UNICANCER R&D for the acquisition of the data.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Region Occitanie [Program “Allocation Doctorale 2017”]; and the SIRIC Montpellier Cancer [Grant INCa_Inserm_DGOS_12553].
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UNICANCER R&D, the sponsor of the PRODIGE 5/ACCORD 17 trial (ClinicalTrials. gov Identifier: NCT00861094), provided permission for the data base access. All participants of the PRODIGE 5/ACCORD 17 trial provided written informed consent. Patient consent was not required for this study as we performed a secondary analysis of existing data.
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Cuer, B., Conroy, T., Juzyna, B. et al. Joint modelling with competing risks of dropout for longitudinal analysis of health-related quality of life in cancer clinical trials. Qual Life Res 31, 1359–1370 (2022). https://doi.org/10.1007/s11136-021-03040-8
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DOI: https://doi.org/10.1007/s11136-021-03040-8