The ICH E9 (R1) addendum describes the concept of estimands in clinical trials. An estimand itself is thereby a systematic description of the treatment effect that should be analysed to answer the objective of a clinical trial including the systematic definition of possible intercurrent events. The use of rescue medication during a clinical trial is an important example of an intercurrent event. Since additional treatments are clinically relevent outcomes that are likely to affect the outcome of the trial, this must be considered when interpreting the study results.  

The aim of this project is to improve the estimation of treatment effects in RCTs permitting rescue medication. A systematic review of RCTs in schizophrenia will be conducted, extracting data on the used methods, analysing efficacy endpoint including rescue medication. Thereby, schizophrenia is a good example of a heterogeneous disorder, where rescue medications could be permitted during clinical trials to prevent drop-outs due to inadequately response or side effects. In a simulation study different analysis strategies will be used to analyse the treatment effect with statistical methods found in the systematic review. Different analysis methods like mixed models with repeated measures and SEMs (Figure) will be compared.