Discernment of mediator and outcome measurement in the PACE trial

When measuring latent traits, such as those used in psychology and psychiatry, it can be unclear whether the instruments used are measuring different concepts. This issue is particularly important in the context of mediation analysis, since for a sound mediation hypothesis the mediator and outcome should be distinct. We sought to assess the extent of measurement overlap between cognitive and behavioural mediators and physical functioning and fatigue outcomes in a large trial of treatments for chronic fatigue syndrome.

A secondary analysis of 640 participants in the "Pacing, graded Activity, and Cognitive behaviour therapy" trial was conducted. Potential measurement overlap was assessed using generalised linear latent variable models where confirmatory factor models quantified the extent to which the addition of cross-loading items significantly improved model fit.

We considered 13 mediators and two outcomes, giving a total of 26 mediator-outcome pairs. Of these, only six showed evidence of cross-loading items, supporting the suggestion that the chosen mediator and outcome constructs were conceptually distinct.

This study highlights how established psychometric methods can be applied to assess measurement overlap in mediation analyses. We found minimal overlap between cognitive and behavioural mediators and physical functioning and fatigue outcomes that are often used in studies of chronic fatigue syndrome. The use of such methods in mediational studies where questionnaires are used to quantify latent traits would add to their robustness and transparency.