The adaptation of the desirability of outcome ranking for interventional clinical trials in epilepsy: A novel consumer‐led outcome measure

Abstract

Interventional clinical trials in epilepsy are typically designed and powered to detect a change in seizure frequency as the primary endpoint, with little consideration given to other benefits or harms of the therapy, or impacts on common epilepsy comorbidities. Desirability of outcome ranking (DOOR) is a novel methodology for evaluating benefits and harms associated with introduction of a new treatment. Multiple outcomes are combined and the resulting combinations are ranked according to their desirability. Herein we describe the adaptation of DOOR for use in therapy trials in epilepsy. Consumers with epilepsy were presented with a selection of measures typically included in epilepsy trials and asked to rank their importance in terms of a desirable outcome and to identify interactions between different seizure control levels and other measures. Seizure control, adverse events, and psychiatric comorbidities were identified as most important, and combinations of these outcomes were ranked to form epilepsy‐DOOR. A separate consumer discussion group verified the appropriateness and accuracy of the ranking. The resultant epilepsy‐DOOR includes 60 possible outcomes, representing high granularity for the assessment of future interventions. It demonstrates the importance of consumer involvement in trial design and presents an alternative to seizure frequency for evaluating new treatments for epilepsy.

Phase II randomised placebo-controlled trial of sodium selenate as a disease-modifying treatment in chronic drug-resistant temporal lobe epilepsy: the SeLECT study protocol

“…Consumers have been involved in the design of this study and will continue to be involved in the ongoing conduct of the trial through the study advisory board. Consumers informed the original adaptation of the epilepsy-DOOR scale, and further refinement of the scale was made at the protocol development forum, where eight consumers finalised the epilepsy-DOOR scale and provided input into other aspects of the study design/protocol 30…”

“…The primary endpoint measure is the epilepsy-DOOR from baseline to week 52 compared between treatment and placebo. At the end of the study each participant will be given an epilepsy-DOOR based on combinations of three outcomes: change in seizure frequency (from baseline to week 52, 4 different categories of outcome), adverse events (presence and severity throughout the 52 weeks, 5 categories of outcome) and change in quality of life (from baseline to week 52, 3 categories of outcome) 30. A summary of the outcomes can be found in table 2.…”

“…Consumers informed the original adaptation of the epilepsy-DOOR scale, and further refinement of the scale was made at the protocol development forum, where eight consumers finalised the epilepsy-DOOR scale and provided input into other aspects of the study design/protocol. 30 …”

“…This epilepsy-DOOR framework has been specifically adapted by people with epilepsy for use in this study combining change in seizure frequency, adverse events, quality of life and medication burden measures into a single outcome measure. 30 The secondary outcome measures will be change in seizure and epileptiform discharge frequency, measured by 8-week seizure diaries and 24 hour EEG recordings; ASM burden, measured using the Liverpool Adverse Event Profile (LAEP); psychiatric comorbidities measured using the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and General Anxiety Disorder 7 (GAD-7); cognitive deficits as measured by the Australian…”

“…The primary outcome measure will be Desirability of Outcome Rank (DOOR). This epilepsy-DOOR framework has been specifically adapted by people with epilepsy for use in this study combining change in seizure frequency, adverse events, quality of life and medication burden measures into a single outcome measure 30…”