On the Practical Application of MMRM to Clinical Trial Data

• Activity Number: 244
• Type: Contributed
• Date/Time: Monday, July 30, 2012 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Scott Andersen*+ and Brian Millen
• Companies: Eli Lilly and Company and Eli Lilly and Company
• Keywords: missing data ; MMRM ; simulations

Abstract

The use of MMRM for clinical trial analyses has recently gained broad support as a primary analysis methodology. Some questions of practical implementation detail remain, however. For example, whether and how to incorporate clinical trial data which is collected at non-protocol-specified timepoints or clinic visits has not been systematically studied. In this paper, we compare different methods for applying MMRM to trials wherein data is available at protocol-specified timepoints, as well as non-protocol-specified timepoints due to patient early discontinuation. The methods under consideration included observed case MMRM, per protocol MMRM, interval LOCF MMRM, and a hybrid of the per protocol and interval LOCF MMRM approaches. Simulation results reveal that the method which best controls the type I error rate is the per protocol method. This method is also associated with the least precision among the competing methods. Thus, in confirmatory clinical trials wherein control of type I error rates is critical, per protocol MMRM is recommended. Points to consider with respect to both study design (e.g., assigning schedule of events) and subsequent analysis are offered.