# The Epilepsy‐Desirability of Outcome Ranking (DOOR) as a Multi‐Faceted Consumer‐Informed Outcome Measure for Epilepsy Clinical Trials

## TL;DR

Epilepsy-DOOR is a new outcome measure for epilepsy drug trials that combines seizure frequency, quality of life, and side effects, offering a more complete view of treatment effectiveness.

## Contribution

Epilepsy-DOOR is a novel, consumer-informed outcome measure that integrates multiple aspects of treatment outcomes in epilepsy trials.

## Key findings

- Epilepsy-DOOR showed benefit for 100 mg brivaracetam in one trial but not smaller doses.
- Epilepsy-DOOR had similar effect sizes to responder rate but slightly reduced power due to including adverse events.
- Epilepsy-DOOR provides a more holistic assessment of treatment effects by balancing benefits and harms.

## Abstract

New drug trials in drug resistant epilepsy are typically powered to detect changes in seizure frequency as the primary endpoint, without integrating other treatment‐associated benefits and harms. We developed Epilepsy‐DOOR, a consumer‐codesigned outcome measure, which combines seizure frequency with quality of life and adverse event measures. This study evaluated Epilepsy‐DOOR in previously completed phase 3 clinical trials of adjunctive brivaracetam in patients with drug resistant epilepsy.

Epilepsy‐DOOR was derived for each participant who completed the randomised controlled trial of three Phase 3 trials of brivaracetam (N01252, N01253, N01254). Win odds were estimated for Epilepsy‐DOOR and its individual components: change in seizure frequency, quality of life, and adverse event severity for treatment with brivaracetam over placebo for each dose in each study. Odds ratio was estimated for responder rate.

In N01252, Epilepsy‐DOOR demonstrated benefit of 100 mg brivaracetam (Win odds 1.42, 95% CI 1.03, 1.97) but not smaller doses over placebo, in line with the results when using responder rate (odds ratio 1.14, 95% CI 1.02, 1.29). In studies N01253 and N01254, benefit as assessed by Epilepsy‐DOOR did not attain statistical significance, despite benefits at some doses when measuring seizure responder rate.

Epilepsy‐DOOR showed similar effect sizes but slightly reduced power when compared with responder rate. This reduced power is due to the appropriate reflection of adverse events by Epilepsy‐DOOR. Epilepsy‐DOOR provides a more holistic measure of anti‐seizure medication treatment effects, balancing relative benefits and harms, and has potential as a future endpoint in clinical trials in epilepsy.

The Epilepsy‐DOOR is a new consumer‐codesigned endpoint for clinical trials of new pharmacotherapies for drug resistant focal epilepsy. Using data from previously completed phase 3 randomised controlled trials, this study demonstrates the Epilepsy‐DOOR detected similar effect sizes to responder rate, providing a more holistic measure of treatment effects which balances benefits and harms in the use of pharmacotherapies for the treatment of focal epilepsy.