Some words about adaptive design

Four rules to adapt by:

• Allocation rule: how subjects will be allocated to the avaialble arms
• Sampling rule: how many subjects will be sampled in subsequent stages
• Stopping rule: when to drop an arm or stop the trial (for efficacy, harm or futility)
• Decision rule: the final decision and interim decisions pertaining to design changes not covered in the previous three rules. Examples of the modifications that can result from these decision-making rules include modifying the sample size, dropping a treatment arm, stopping a study early for success or failure, combining phases, and/or adaptive randomization

Adaptive trials can involve any one of these rules, or a combination of them

Top three misconceptions of adaptive trials:

• There are certain areas of confirmatory clinical research where adaptive designs are more applicable and other areas where adaptive designs are less or not applicable
• Adaptive trial designs are characterized by unmanageable complexity and less careful planning
• Adaptive designs require smaller sample sizes than traditional designs

Human beings lean toward wishful thinking. On average, drug effects are overestimated and the variability of drug effects is underestimated. As yet, trials have either been unknowingly underpowered or intentionally overpowered. In the latter case, an adaptive design is more or less unnecessary (aside from the questionable ethics of overpowered trials). The unknowingly underpowered trials, however, is where adaptive designs come into plan. By using an adaptive design, a potentially underpowered trial can be rescued. Overall, adaptive designs make better use of the patient as a resource. Trials no long need to be overpowered, and the number of underpowered trials is rescued.