Informing the selection of futility stopping thresholds: case study from a late-phase clinical trial
Article first published online: 27 MAR 2008
Copyright © 2008 John Wiley & Sons, Ltd.
Volume 8, Issue 1, pages 25–37, January/March 2009
How to Cite
Hughes, S., Cuffe, R. L., Lieftucht, A. and Garrett Nichols, W. (2009), Informing the selection of futility stopping thresholds: case study from a late-phase clinical trial. Pharmaceut. Statist., 8: 25–37. doi: 10.1002/pst.323
- Issue published online: 9 MAR 2009
- Article first published online: 27 MAR 2008
- stopping rule;
- conditional power;
- decision analysis;
- group sequential
In an environment where (i) potential risks to subjects participating in clinical studies need to be managed carefully, (ii) trial costs are increasing, and (iii) there are limited research resources available, it is necessary to prioritize research projects and sometimes re-prioritize if early indications suggest that a trial has low probability of success. Futility designs allow this reprioritization to take place. This paper reviews a number of possible futility methods available and presents a case study from a late-phase study of an HIV therapeutic, which utilized conditional power-based stopping thresholds. The two most challenging aspects of incorporating a futility interim analysis into a trial design are the selection of optimal stopping thresholds and the timing of the analysis, both of which require the balancing of various risks. The paper outlines a number of graphical aids that proved useful in explaining the statistical risks involved to the study team. Further, the paper outlines a decision analysis undertaken which combined expectations of drug performance with conditional power calculations in order to produce probabilities of different interim and final outcomes, and which ultimately led to the selection of the final stopping thresholds. Copyright © 2008 John Wiley & Sons, Ltd.