Table 4.
Issues to be considered before selection of antiepileptic therapies for clinical testing
| Recommendations | |
|---|---|
| Species | Insufficient information is available to recommend efficacy testing in more than one species. Toxicity testing in at least two species is, however, a regulatory requirement |
| Sex | One sex might be sufficient for a particular study, but both male and female animals should be tested before Investigational New Drug (IND)-enabling studies |
| Age | Antiepileptic therapies intended for use in newborn babies, infants, or children should be tested in age-specific models |
| Animal model | Testing in at least two different animal models (if more than one validated model is available) might inform on the validity of the findings and the broadness of the therapeutic indications of the antiepilepsy therapy. Cautionary interpretation of disparate results is advised if the predictive validity of a model is unknown |
| Tolerability in a disease model | Tolerability testing in disease models might identify relevant toxicities that do not occur in healthy animals |
| Intent of intervention | Testing for antiepileptogenesis, disease modification, or antiseizure effects in animal models should mirror intended future trials in human beings |
| Therapeutic window | Obtaining information on the optimum therapeutic timepoint of intervention or dose range is advised. Care should be taken to avoid studies that intervene at a timepoint that cannot be duplicated in human trials (eg, before insult) |
| Target validation in humans | Validation of the target mechanism in human beings might help to de-risk selection of promising therapies for clinical testing |