Monotherapy trials: endpoints

Monotherapy antiepileptic drug (AED) trials call optimally provide informat ion concerning efficacy and tolerability of one drug compared with placebo. as well as to different doses or rates of administration. Commonly, a drug is compared with one or more other drugs. The outcome measures will be dic tated by the questions being asked. In most comparative studies, the single overall result that best defines success or failure is time of continuatio n on drug as expressed in a life table. Discontinuation before planned comp letion of the study implies insufficient efficacy or unacceptable adverse e ffects. A statistically significant difference between treatments provides important support for recommending the drug or dose with the best outcome. The criteria for continuation/discontinuation are defined in the design bas ed on the expected outcome. The outcome of primary importance is efficacy i n prevention of seizures or a decrease in severity. Complete control for th e duration of the study is the ultimate goal but in some populations may no t be possible. The number of subjects entering remission gives further info rmation about long term outcome. Time to first (nth) seizure provides simil ar evidence of efficacy. Seizure rates allow comparisons of subjects retain ed for different lengths of time in the trial. Differences in seizure sever ity may be of clinical importance and multiple efforts have been made to de velop instruments to accurately measure this outcome. Adverse effects of th e drugs are tile second major outcome. These call be expressed as incidence and/or prevalence. The presence and frequency of side effects will depend on how the study is designed and whether these effects are specifically sou ght by the investigators. Serious systemic safety outcomes art: monitored, but the relative infrequency of occurrence and number of subjects in thc tr ials usually do not provide enough power to detect statistically significan t differences except for rash. Tolerability is more easily documented but i s difficult to access accurately in the absence of placebo controls. Freque ncy, severity and persistence are measurable. Specific unwanted types of dr ug effects can be specifically studied using detailed neuropsychological te st batteries. Some information concerning pharmacokinetic properties may be obtained but are better assessed in other types of trials. A final importa nt outcome is the effect of drug therapy on duality of life. Although a fav orable finding in this outcome is most desirable, the measures used are muc h less precise than those for efficacy and adverse effects. (C) 2001 Publis hed by Elsevier Science B.V.