“Get Real with Stopping Rule”-Evaluating the Value of being able to Stop Early using the Real Option Framework

Abstract

Background: Stopping a trial incurs significant cost and thus this is not a decision that should be taken lightly. Data Monitoring Committee (DMC) is recommended to understand all options and their respective implications. Since this is a complicated decision, people often adopt some “rule of the thumb” guidelines rather than a comprehensive framework to assess the pros and cons. This article is a first step toward a unified approach to trial. It should be noted that the use of monetary amount is for illustration only-it is just a medium of a collective value and this is not unlike the use of Qualityadjusted Life Year (QALY). The framework is still valid if other measures such as utility are used instead. This article will review some major elements in making early stopping decision and then it will explain how a real option framework can be used to quantity the cost and the benefit of being able to make such decision. Method: This article proposes an analytical framework based on real option concept to estimate the cost and the benefit of being able to stop a trial early. Results: Flexibility usually is associated with some implicit and explicit additional cost. This method allows one to quantity the benefit of being able to stop early and thus one can make a more informed decision on whether to acquire that early stopping possibility intrial design. The information contained in an early-stopped AIDS trial is used to illustrate this. Conclusion: The challenges of stopping rules are discussed and then a real option approach to evaluate the value of being able to stop a trial early is proposed. This approach allows us to put the value of this choice into a boarder perspective and thus we are able to quantify the cost of early stoppage. This novel technique allows the trial designers to decide if they should incorporate the early stopping flexibility in their clinical trials.