title: Application of a stopping rule based on total treatment failures: the postoperative Crohn's disease trial.
abstract: The Postoperative Crohn's Disease Trial (PCDT), a placebo-controlled randomized trial of Rowasa I in the prevention of postoperative recurrence of Crohn's disease, is used as an example of how a stopping rule based on total endpoint occurrences can provide considerable advantage over standard fixed sample size methods. It can be used when the primary outcome is occurrence or time to occurrence and does not raise the troublesome issues regarding the unblinding of group differences that other sequential methods create. The main advantage of the total endpoint stopping rule is that it provides set power. Standard fixed sample size designs provide a given power only on average. The power actually achieved in a particular fixed sample size trial is largely determined by the overall observed rate of endpoint occurrences. This claim about the total endpoint stopping rule is well established in the statistical literature and, as well as outlining the mathematical details in an Appendix, we use computer simulation of the PCDT to demonstrate that use of the stopping rule will allow termination of the trial while maintaining power and type I error at a predetermined level.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: A H
authors.initials: AH
authors.lastname: Steinhart
authors.forename: K
authors.initials: K
authors.lastname: O'Rourke
authors.forename: B G
authors.initials: BG
authors.lastname: Wolff
authors.forename: R S
authors.initials: RS
authors.lastname: McLeod
mesh_terms: D000636:Aminosalicylic Acids / Q000627:therapeutic use*; D003198:Computer Simulation; D003424:Crohn Disease / Q000517:prevention & control* / Q000601:surgery; D004311:Double-Blind Method; D006801:Humans; D019804:Mesalamine; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic / Q000191:economics / Q000379:methods*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000636:Aminosalicylic Acids; D019804:Mesalamine