How to process data from clinical trials and their open label extensions

Data handling of pivotal clinical trials and their open label extensions is always a challenging task. Using the latest methods of Electronic Data Capture (EDC) correctly combined with the powers of SAS we can meet this challenge successfully. An open-label extension can accept patients from more than one trial of the same study drug. All the trials leading to the same open-label extension are considered “main phase”. The open-label extension can be called “extension phase”. An interim analysis is done on the main phase, and safety analyses are done on the extension phase taking into account the ‘main phase’ data as well. One of the biggest challenges is to decide how to use EDC correctly in such a scenario. Before collecting or combining data there is a choice to make. It is how to set up EDC. One option is to include both the main and extension phase together in one database and split them later. The other option is to create two databases, one for each phase, and then reconcile them later. INTRODUCTION Patients participating in double-blind controlled pivotal trials are often transferred into long-term open label extension trials after completion of the main part of the trial. These trials are often requested to offer patients benefiting from a new drug treatment the possibility to receive the drug until market launch and to generate long-term safety data. Although these long-term extension trials cannot be regarded as entirely independent from the double-blind trials, there are good reasons to separate them under another study number. One reason is that patients that were part of the placebo or comparator group in the original trial may take the investigational drug in the extension trial. From a data management point of view, different strategies can be applied to handle a controlled trial followed by long-term extension trials. The purpose of the paper is to show what could be gained and lost if such trials are set up with an EDC system – either as two EDC databases or as one EDC database for both trials with a later split in two SAS DBs with appropriate study numbers. The latter solution will be presented as the actually preferred one. INITIAL SITUATION Extension trials following pivotal trials can be planned in several different ways. You can find them combined within one study protocol under one study number as well as separated in two study protocols with an extra study number for each. Another kind of extension planning is to have one extension trial as a pool study of several different main trials. Thinking of how to collect and transfer the data of such trials into the desired database structures leads to two main options. One option includes the set up of the pivotal and the extension trial in an EDC system under one study number. These studies are divided into two parts consisting of a main phase ending up in an interim analysis and an open-label extension phase focusing on the collection of safety data. Another option is to set up the two phases as two studies separately in the EDC system. The first option we call the SAS approach as SAS would be used to split the data into two databases, the second we call the EDC approach because separation of data would already take place in the EDC system (see figure 1).