OBJECTIVES: The objective of this study was to review the trends in design of pivotal clinical trials for Partial Onset of Seizures. METHODS: Systematic review was conducted to identify new and on-going pivotal clinical for Partial Onset of Seizures. The inclusion criteria were the indication of Partial Onset of Seizures and study completion date of 2016 or after. The data field extracted were study title, intervention, sponsor, age subgroups, planned enrollment, study type, study design, completion date and outcome measures. RESULTS: Overall, 18 Phase III clinical studies with total planned enrollment of 5528 patients were identified. The median enrollment for the studies was 296 patients. All of the studies were for drugs. Three of the eighteen studies were for monotherapy, while others were for add-on, adjunctive or long term safety and efficacy. The primary outcome measures varied significantly across trials. The percent change in seizure frequency per 28 days was the most common (4 out of 18 trials) outcome across these trials. Other primary outcome measures included: Time to treatment failure, proportion of subjects who are seizure free, seizure frequency, change in average daily frequency (ADF) of electrographic partial-onset seizures, Percent reduction of 24 hour seizure rate, Response rate and 50% reduction from baseline in partial-onset seizure frequency. The secondary outcome measures also varied significantly across trials. The secondary outcomes included: Percentage of Seizure Free Days at the End of Year 1, responder rates (50% or more reduction), Percent change in the partial seizure frequency per 28 days, Proportion of subjects in the ITT set without a seizure during the 26-week Evaluation Period, Proportion of subjects remaining seizure free for 6 consecutive months.  CONCLUSIONS: Lack of consistent primary and secondary outcomes across Partial Onset of Seizure trials might impose some challenges in demonstrating comparative effectiveness.