Our objective was to define responder criteria using an anchor-based approach for frequency of
cataplexy attacks and excessive daytime sleepiness in narcolepsy patients undergoing sodium oxybate
treatment. We used pooled data from two randomized, placebo-controlled, double blind, multi-center
4-week and 8-week trials of sodium oxybate for narcolepsy with cataplexy and analyzed using receiver
operator characteristics analysis. Percent change in frequency of weekly cataplexy attacks and the
Epworth Sleepiness Scale outcomes were compared to Clinical Global Impression of Change ratings,
used as the anchor to define true response. Participants (n=336) were 39% male, 89% white, with a
mean age of 41.5 (15.3), reporting a median of 20.5 cataplexy attacks per week and a mean Epworth
Sleepiness score of 17.5 at baseline. A majority (51%) were much or very much improved based on
Clinical Global Impression of Change ratings, considered a true response to treatment. Area under the
curve values for % reduction in cataplexy attacks (77%) and % change in sleepiness score (78%)
supported response definition thresholds of 46% and 12%, respectively. Classification using either
response definition agreed with the anchor for approximately 71% of participants. Cataplexy response
definition was more sensitive (Cataplexy=0.77, ESS=0.69) while sleepiness was more specific
(Cataplexy=0.66, ESS=0.75). Both responder definitions showed a dose response relationship with
sodium oxybate demonstrating their validity using an external criterion. Weekly cataplexy attacks and
ESS can be used to help document clinical response to narcolepsy treatment using criteria of 46% and
12% reductions, respectively