Principles of New Trial Designs and their Practical Implications

Adaptive designs are relatively flexible clinical trial designs, allowing for modifications during the course of the trial in order to streamline and optimise the process. Analyses of the accumulating study data are performed at pre-planned time points within the trial (interim analysis), can be performed in a fully blinded or unblinded manner, and can occur with or without formal statistical hypothesis testing. Adaptive designs allow for real-time learning during the course of a trial; they are relatively flexible as they allow for modifications during the course of the trial, in order to streamline and optimise the process. It is important that the process is modified only in such a way that the validity and integrity of the trial are not affected.

Adaptive designs can pose operational challenges because of their complexity, and the process of adapting a trial can introduce bias. This bias can be either statistical or operational – for example, if an adaptation suggests that the results of a trial point in a certain direction.

The adaptive design may improve trial efficiency for the sponsor and the participants in the trial. However, if it is not properly conducted, there is a high risk that such a trial can generate clinical results that are difficult to interpret or translate into daily practice.