title: A Rescue Strategy for Handling Unevaluable Patients in Simon's Two Stage Design.
abstract: For phase II oncology trials, Simon's two-stage design is the most commonly used strategy. However, when clinically unevaluable patients occur, the total number of patients included at each stage differs from what was initially planned. Such situations raise concerns about the operating characteristics of the trial design. This paper evaluates three classical ad hoc strategies and a novel one proposed in this work for handling unevaluable patients. This latter is called the rescue strategy which adapts the critical stopping rules to the number of unevaluable patients at each stage without modifying the planned sample size. blue Simulations show that none of these strategies perfectly match the original target constraints for type I and II error rates. Our rescue strategy is nevertheless the one which best approaches the target error rates requirement. A re-analysis of one real phase II clinical trials on metastatic cancer illustrates the use of the proposed strategy.
authors.affiliation: Biostatistics department, Hôpital, Institut Curie, Paris, France; UMR 1178, INSERM, Villejuif, France.
authors.forename: Lisa
authors.initials: L
authors.lastname: Belin
authors.affiliation: UMR 1178, INSERM, Villejuif, France; Université Paris Sud, Villejuif, France; Hôpital Paul Brousse, AP-HP, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Broët
authors.affiliation: Epidemiology and Clinical Research department, Hôpital Bichat, AP-HP, Paris, France; Centre de pharmacoépidémiologie (Cephepi), Hôpital Bichat, AP-HP, Paris, France; UMR 1123 ECEVE, Université Paris Diderot, Sorbonne Paris Cité, Paris, France; UMR 1123 ECEVE, INSERM, Paris, France; CIC-EC 1425, INSERM, Paris, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: De Rycke
mesh_terms: D000465:Algorithms; D015982:Bias; D001932:Brain Neoplasms / Q000532:radiotherapy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D017322:Clinical Trials, Phase II as Topic / Q000379:methods / Q000592:standards*; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D012107:Research Design / Q000592:standards*; D018401:Sample Size