The handling, analysis and reporting of missing data in patient reported outcome measures for randomised controlled trials

Thesis

Missing data is a potential source of bias in the results of randomised controlled trials (RCTs), which can have a negative impact on guidance derived from them, and ultimately patient care.

This thesis aims to improve the understanding, handling, analysis and reporting of missing data in patient reported outcome measures (PROMs) for RCTs.

A review of the literature provided evidence of discrepancies between recommended methodology and current practice in the handling and reporting of missing data. Particularly, missed opportunities to minimise missing data, the use of inappropriate analytical methods and lack of sensitivity analyses were noted.

Missing data patterns were examined and found to vary between PROMs as well as across RCTs. Separate analyses illustrated difficulties in predicting missing data, resulting in uncertainty about assumed underlying missing data mechanisms.

Simulation work was used to assess the comparative performance of statistical approaches for handling missing available in standard statistical software. Multiple imputation (MI) at either the item, subscale or composite score level was considered for missing PROMs data at a single follow-up time point. The choice of an MI approach depended on a multitude of factors, with MI at the item level being more beneficial than its alternatives for high proportions of item missingness. The approaches performed similarly for high proportions of unit-nonresponse; however, convergence issues were observed for MI at the item level. Maximum likelihood (ML), MI and inverse probability weighting (IPW) were evaluated for handling missing longitudinal PROMs data. MI was less biased than ML when additional post-randomisation data were available, while IPW introduced more bias compared to both ML and MI.

A case study was used to explore approaches to sensitivity analyses to assess the impact of missing data. It was found that trial results could be susceptible to varying assumptions about missing data, and the importance of interpreting the results in this context was reiterated.

This thesis provides researchers with guidance for the handling and reporting of missing PROMs data in order to decrease bias arising from missing data in RCTs.

Authors: Rombach, I

• DOI: 10.5287/ora-xvgaznqoe
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Multiple imputation; Randomised controlled trials; Missing data
• Subjects: The handling, analysis and reporting of missing data in patient reported outcome measures for randomised controlled trials