title: How predictive are photosensitive epilepsy models as proof of principle trials for epilepsy?
abstract: OBJECTIVE
  Human photosensitive epilepsy models have been used as proof of principle (POP) trials for epilepsy. Photosensitive patients are exposed to intermittent photic stimulation and the reduction in sensitivity to the number of standard visual stimulation frequencies is used as an endpoint. The aim of this research was to quantify the predictive capabilities of photosensitive POP trials, through a survey of current literature.
  
  
  METHODS
  A literature search was undertaken to identify articles describing photosensitive POP trials. Minimally efficacious doses (MEDs) in epilepsy were compared to doses in the POP trials that produced 50-100% response (ED50-100). Ratios of these doses were calculated and summarised statistically.
  
  
  RESULTS
  The search identified ten articles describing a total of 17 anti-epileptic drugs. Of these, data for both MED and ED50-100 were available for 13 anti-epileptic drugs. The average ratio of MED to ED50-100 was 0.95 (95% CI 0.60-1.30). The difference in MED to ED50-100 ratios between partial epilepsy (0.82) was not significantly different from that of generalised epilepsy (1.08) (p=0.51).
  
  
  CONCLUSIONS
  Photosensitive POP trials are a useful tool to quantitatively predict efficacy in epilepsy, and can be useful as early and informative indicators in anti-epileptic drug discovery and development.
authors.affiliation: Eli Lilly and Company, Erl Wood Manor, Windlesham, Surrey GU20 6PH, United Kingdom. Electronic address: yuenes@lilly.com.
authors.forename: Eunice S M
authors.initials: ES
authors.lastname: Yuen
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Sims
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods*; D004828:Epilepsies, Partial / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D004827:Epilepsy / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D020195:Epilepsy, Reflex / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008959:Models, Neurological; D010775:Photic Stimulation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants
keywords: Drug development; Epilepsy; Photosensitive; Proof of principle