Multi-Arm Multi-Stage (MAMS)


Measures to minimise operational bias

PANDA readers should cross-reference measures to minimise operational bias under general considerations for background discussion on this subject.

The decision-making at the interim analyses is one of the most challenging aspects of MAMS designs. In order to ensure that the trial’s integrity is maintained, it is suggested that an independent board (e.g., the data and safety monitoring board) makes a recommendation on the basis of unblinded data and predefined rules to the relevant group (e.g., trial steering group or committee) which is then expected to adopt this recommendation. Examination of unblinded data by the steering group and investigators should be avoided. To ensure this process runs smoothly, it is recommended that the rules for selection and stopping are discussed extensively with the investigators and steering group prior to the study and prior to conducting any interim analysis to ensure consensus from all parties.

Other aspects that need special attention include patient information sheets and how to obtain informed consent. As the number of arms could change in the course of the study, it is recommended that the information sheets are made for all possible outcomes post interim analysis to minimise delay in implementing the interim decision.

Other relevant considerations include planning time for the study design and setup, drug supply and staff contracts (see general considerations).