New statistical method for analyzing time to first seizure: example using data comparing carbamazepine and valproate monotherapy.
BACKGROUND
Time to first seizure is a common outcome in antiepileptic drug (AED) studies. Previous studies have typically failed to find statistically significant differences between carbamazepine (CBZ) and valproate (VPS). We re-analyzed a meta-analysis comparing CBZ and VPS monotherapy with new powerful statistical methods that incorporate baseline seizure rate information.


METHODS
Individual patient data were available on 1,265 patients from a meta-analysis of five trials. The outcome measure was time to first seizure after randomization, adjusted for background variables and baseline seizure rate.


RESULTS
We found strong evidence of an interaction between treatment and epilepsy type, and between treatment and age. For generalized onset seizures, VPS was statistically significantly better than CBZ: VPS delayed the first seizure after treatment 58%, 52%, 44%, and 36% longer than CBZ for individuals aged 10, 20, 30, or 40, respectively. For partial onset seizures in individuals older than 30, CBZ was significantly better then VPS; CBZ delayed the time to first seizure by 9%, 25%, 44%, and 66% longer than VPS for individuals aged 20, 30, 40, or 50, respectively.


CONCLUSIONS
The results show clear age-varying differences between the effectiveness of CBZ and VPS for generalized onset and partial onset seizures, which have not been identified in previous studies using standard statistical methods. In future trials of AED monotherapy or add-on where time to first or Nth seizure is an outcome, methodology that can incorporate baseline seizure rate information would allow more powerful comparisons between treatments or between treatment and placebo.
Cowling
Benjamin J
BJ
Department of Community Medicine and School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. bcowling@hku.hk
Shaw
J Ewart H
JE
Hutton
Jane L
JL
Marson
Anthony G
AG
D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use*; D002648:Child; D003627:Data Interpretation, Statistical; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000188:drug therapy; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy*; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid