Abstracts

Seizure free rates in clinical trials are either not reported, or reported by such differing methodology that the rates cannot be compared from trial to trial. Often, publications report seizure free results using intention to treat, last observation carried forward (ITTLOCF). In this type of analysis, patients who are seizure free until discontinuation, even if this occurs early in treatment, will be counted as seizure free, potentially inflating the rate. Completer analysis, in comparison, only counts patients as seizure free if they complete the specified treatment period. The goal of this study is to provide clinically useful, previously unpublished comparative analyses of seizure freedom rates for the newer antiepileptic drugs (AEDs) on the market, using both ITTLOCF and completer analyses. Data was reviewed from published clinical trials of the new generation of AEDs, used as add-on therapy in patients with refractory partial seizures. This included gabapentin (GPN), lamotrigine (LTG), topiramate (TOP), tiagabine, oxcarbazepine (OXC), levetiracetam (LEV), zonisamide (ZNS) and pregabalin (PGB). Pharmaceutical companies were then contacted for the provision of unpublished seizure-free data, including rates in the completer population. Unpublished data were obtained for GPN, LTG, PGB, LEV, and ZON. The ITTLOCF analysis in several AED studies reported a higher rate of seizure freedom compared to the seizure-free rates in the completer population. These included OXC (ITTLOCF 22%, completers 9%), PGB (ITTLOCF 3.7-7.9%, completers 1.3-1.4%), and ZNS (ITTLOCF 5.1%, completers 1.7%). There was little difference for LEV (ITTLOCF 3.9-6.4%, completers 3.9-7.1%), and LTG (ITTLOCF .7%, completers .8 %) Depending on doses used, 0%-1.1% of the ITT population were seizure-free in the GPN trials. Data was not available to assess the completer population. By employing the method of last observation carried forward, a clinically unrealistic picture of seizure-free rates may be reported. The completer data may be a more clinically accurate seizure freedom analysis, as it includes only those patients who are able to tolerate the drug. In addition, the inclusion of titration periods where subtherapeutic doses are initially used can make seizure-free rates appear diminished. Clinical trials should therefore report all data from both ITT and completer populations, and exclude titration periods in order to provide information that is more useful in clinical decision-making.