Planning and Executing Response-Adaptive Learn-Phase Clinical Trials: 1. The Process

The planning and execution of clinical trials utilizing response-adaptive allocation involves complexities beyond those encountered in the planning and execution of more traditional trial designs. How the adaptive design will optimize the drug development process must be clearly defined; an appropriate endpoint must be selected to drive the adaptive design engine, and steps must be taken to ensure that the data required for adaptive decision making will be available in a timely fashion during the trial. Trial simulations are essential during the planning stage to develop appropriate decision rules and the response-adaptive allocation algorithm. Structures such as data monitoring committees and independent statistical centers help to ensure the validity and integrity of the trial, while facilitating decision making during the trial.