Abstract

The International League Against Epilepsy has recommended retention time, defined as the time to withdrawal of the randomised drug or addition of another, be one of the primary endpoints for clinical trials of anti-epileptic drugs (AEDs). Patients may decide to withdraw from such treatment because of intolerable side effects or poor seizure control. Further, quality of life (QoL) is increasingly recognised as an important outcome in epilepsy and a significant proportion of patients report emotional and social impairments as a consequence of the AEDs and their epilepsy. There is a concern that these impairments may worsen over time. However, in the presence of a potentially informative event of AED withdrawal, modelling longitudinal QoL profiles alone may be misleading. The aim of this work is to simultaneously investigate the differential treatment effects on competing risks of drug withdrawal and quality of life in newly-diagnosed patients with epilepsy.

Standard methods for joint modelling of longitudinal and survival data have one failure type and an assumption of independent censoring. In this study we consider joint modelling of the competing risks (dependent censoring) of drug withdrawal and the repeated measurements of quality of life. We fit a cause-specific hazards model to allow for competing risks, with a separate association parameter for each AED withdrawal reason, and a combined analysis is undertaken. We present results on the gain from a combined analysis over the approach fitting separate models.

Acknowledgment: This work is funded by MRC Grant G0400615