The ethics of excluding women who become pregnant while participating in clinical trials of anti-epileptic medications

SummaryIntroductionThe bioethical principles of autonomy, beneficence, non-maleficence and justice, complemented by ethics committee evaluation, define conduct of clinical trials of anti-epileptic medications (AEM).Background informationIncreased teratogenicity for offspring of women with epilepsy is presented in both lay and scientific literature.Specific drugs—older generationTeratogenicity of phenobarbitone (PB), phenytoin (PHT), valproate (VPA) and carbamazepine (CBZ) is acknowledged, with drugs, such as trimethadione, being removed from the market because of teratogenicity.Specific drugs—new generationInsufficient data allowed definitive commentary concerning teratogenicity of newer AEM, such as lamotrigine (LTG), gabapentin (GBP), tiagabine (TGB) or levetiracetam (LEV). All those suggestions favour some over others with specific AEM combinations being questioned.Pregnancy registriesLack of information sporn AEM-specific plus national and international birth registries which endorse VPA, CBZ and LTG dose related concerns.Conflict of interestCompeting influences of AEM and epilepsy-specific factors need delineation although appear more teratogenetic than does epilepsy alone.Clinical trialsMost trials focus upon refractory epilepsy with potentially enhanced risks. Informed consent demands discussion of possible teratogenicity and exclusion of women unwilling to practice adequate contraception.DiscussionTrials must respect legal and ethical dictates including the exclusion of women unwilling to practice reliable contraception. Automatic exclusion from a trial, subsequent to confirmed pregnancy, is unlikely to protect the foetus as potential for teratogenicity already has occurred. Autonomy should empower prospective parents to decide continued trial participation consequent to detailed informed consent without coercion. All options demand review, including responsibility to future AEM users.