Incorporating scientific,ethical and economic considerations into the design of clinical trials in the pharmaceutical industry: a sequential approach

A flexible sequential approach to the design of clinical trials is discussed herein. This approach is based on a “confidence sequence” viewpoint instead of the rigid stopping and terminal decision rules in conventional sequential testing theory. By using an appropriate confidence sequence, one can always ensure a prescribed degree of scientific rigor (confidence) in establishing the drug to be effective. Moreover, one also has the option of terminating the trial early when there is already enough statistical evidence for concluding that the drug is effective, or when the drug shows uniorseen harmful effects, or when the data predict that there is little chance of arriving at a definitive conclusion in favor of the drug by the scheduled end of the trial. We discuss how these and other ethical and economic considerations can be readily incorporated into the stopping criteria of the trial.