Ethical issues in antiepileptic trials: old issues in a new world.

Abstract

Clinical trials of new antiepileptic drugs and therapies raise a number of challenging issues. Some would call them methodological issues. Others would call them safety issues. Still others would focus on ethical issues. Taking them altogether, they should be called responsibility issues. Responsible conduct of human studies of epilepsy, its pathophysiology, and its therapy, as in any clinical condition, must, of course, consider study design, procedures, safety, and ethics. These essential components cannot be separated, nor can the responsibility for ensuring that all studies are sound in all respects. The goals of scientists, of their subjects, and of society are ultimately shared goals; there may be differing emphasis and competing interests, but all parties to the research mission share common goals and share a common responsibility to ensure that studies are properly designed and conducted with all these elements in mind. At least four perspectives must be considered in human trials: those of the investigators, the sponsors, the subjects, and the research ethics review board (RERB), which used to be called the institutional review board, or IRB. Traditionally, the interests of sponsors and investigators have been aligned and linked together, as are those of the subjects and IRBs. These pairings have contributed to a confrontational environment, one that began with the imposition on the scientific and corporate communities of regulations for protection of human subjects in research, an environment that has existed for the past three decades. This paradigm pits the interests of those who want to do research against those on whom it will be done. Consider, for example, a 15-year-old female patient with a history of grand mal seizures since 2 years of age. She has taken four different drugs over the years, is now stable, has been without seizures for >1 year, and is succeeding in school. Her medication is reasonably well tolerated, except for severe gingival hyperplasia. This has been on her mind lately as she is getting ready to attend her junior prom.