AN EXTENSION OF STOCHASTIC CURTAILMENT FOR INCOMPLETELY REPORTED AND CLASSIFIED RECURRENT EVENTS - THE MULTICENTER STUDY OF HYDROXYUREA IN SICKLE-CELL-ANEMIA (MSH)

The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), a do uble-blind randomized clinical trial, compared the frequency of acute vaso-occlusive (painful) crises during 2 yr of follow-up in 299 patien ts randomly assigned to hydroxyurea or placebo. Most patients had more than one crisis; all crises reported were included in the primary out come analysis. A total of 7,229 follow up medical contact reports were classified as crises/not crises by a Crisis Review Committee. Because of the time required to report, document, and classify contacts, inte rim analyses were prepared with incomplete data. If a stopping boundar y were crossed, early termination could be advised only after assessin g the potential impact of the incomplete data. In an extension of stoc hastic curtailment methods, simulation procedures were used to estimat e the probability of detecting differences when group crisis rates pro jected to the end of the study were compared using a rank test. To acc ount for medical contacts not yet reported and the future occurrence o f crises, Poisson process models assuming no treatment effect on crisi s rates were used for these simulations. The number of unclassified co ntacts that would be classified as crises was simulated as a binomial random variable. These methods may be useful for interim monitoring in other studies of recurrent events with ongoing event reporting and cl assification. (C) Elsevier Science Inc. 1997.