Background
Clinical trials require large monetary and time commitments and should provide information on both whether and how treatments work. Treatment mechanisms can be studied using mediation analysis, allowing refinement of treatments. Mediation studies often use only single contemporaneous measures of mediator and outcome limiting the conclusions that can be drawn. Longitudinally measured mediators and outcomes, such as those in the Pacing, Graded Activity, and Cognitive Behaviour Therapy: A Randomised Evaluation trial (PACE, ISRCTN 54285094) allow for more realistic estimates of mediated effects.