Open Label Extension Analysis - Exploring Self-Controlled Case Series Methodology

Open Label Extension Analysis - Exploring Self-Controlled Case Series Methodology

Randomised trials are a very good way of being able to test whether a medication is able to treat an illness, and whether it causes adverse reactions. This is because, when it is done well, randomisation between medication treatment groups means the only difference between the groups is the treatment received. Any difference observed in outcomes between the groups can then be concluded to be caused by the treatments themselves. Sometimes, at the end of a randomised trial, all patients who took part are offered the opportunity to take the medication the investigators are most interested in, and people who accept this offer are then followed up and further data is collected. This is called an "Open Label Extension" or OLE. In an OLE, the benefits of treatment randomisation no longer apply and we do not have well establised methods for analysing the data that are collected. In this proposal we will explore how well a study methodology that is well established for analysing data from non-randomised studies works for OLE studies. This method is called the "Self-Controlled Case Series" (SCCS), and the most important feature of the method is that people act as their own controls. This means we make comparisons between periods of time when people were receiving a medication with periods of time when the same people were not receiving the medication.The study will use data from an OLE study of belimumab, a treatment for systemic lupus erythematosus. Using these data we will firstly look at the data to see if it meets some important requirements of SCCS methodology. If it does, we will then assemble the data in a format that allows us to analyse the data and determine whether we can detect the known association between belimumab and infections.Based on our findings we will be able to make recommendations about whether the SCCS is a potentially useful technique for analysing OLE data and whether there is any need for future OLE studies to collect data in different ways to better allow the use of this methodology.