The futility index. An approach to the cost-effective termination of randomized clinical trials.

Although the randomized clinical trial is recognized as the method of choice for evaluating therapeutic innovations, it is often enormously expensive--in some instances, as a result of the unnecessary continuation of a trial destined to conclude that an innovation is not superior to standard therapy. Although most large clinical trials in which results evolve over time are monitored for early evidence of efficacy or toxicity, trials are rarely terminated because the probability of a positive result regarding the value of the innovation has become low. This paper discusses the issues involved in the monitoring and early termination of long-term clinical trials and describes the futility index, a probabilistic basis for early termination of trials of innovative therapy when the accumulated data imply small probability of success. Utilization of the futility index in the management of clinical trials of innovations can be of value in reducing, at slight loss of power, the number of unproductive studies carried to completion, thereby creating new opportunities for more effective use of limited resources.