Performance status and trial site-level factors are associated with missing data in palliative care trials: An individual participant-level data analysis of 10 phase 3 trials

摘要

Background: Missing data compromise the internal and external validity of trial findings, however there is limited evidence on how best to reduce missing data in palliative care trials. Aim: To assess the association between participant and site level factors and missing data in palliative care trials. Design and setting: Individual participant-level data analysis of 10 phase 3 palliative care trials using multi-level cross-classified models. Results: Participants with missing data at the previous time-point and poorer performance status were more likely to have missing data for the primary outcome and quality of life outcomes, at the primary follow-up point and end of follow-up. At the end of follow-up, the number of site randomisations and number of study site personnel were significantly associated with missing data. Trial duration and the number of research personnel explained most of the variance at the trial and site-level respectively, except for the primary outcome where the amount of data requested was most important at the trial-level. Variance at the trial level was more substantial than at the site level across models and considerable variance remained unexplained for all models except quality of life at the end of follow-up. Conclusion: Participants with a poorer performance status are at higher risk of missing data in palliative care trials and require additional support to provide complete data. Performance status is a potential auxiliary variable for missing data imputation models. Reducing trial variability should be prioritised and further factors need to be identified and explored to explain the residual variance.