Evaluation of Treatment Effect with Paired Failure Times in a Single-Arm Phase II Trial in Oncology.
Fiche publication
Date publication
janvier 2018
Journal
Computational and mathematical methods in medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BOUCHE Olivier
Tous les auteurs :
Texier M, Rotolo F, Ducreux M, Bouché O, Pignon JP, Michiels S
Lien Pubmed
Résumé
In early phase clinical trials of cytotoxic drugs in oncology, the efficacy is typically evaluated based on the tumor shrinkage. However, this criterion is not always appropriate for more recent cytostatic agents, and alternative endpoints have been proposed. The growth modulation index (GMI), defined as the ratio between the times to progression in two successive treatment lines, has been proposed for a single-arm phase II trials. The treatment effect is evaluated by estimating the rate of patients having a GMI superior to a given threshold. To estimate this rate, we investigated a parametric method based on the distribution of the times to progression and a nonparametric one based on a midrank estimator. Through simulations, we studied their operating characteristics and the impact of different design parameters (censoring, dependence, and distribution) on them. In these simulations, the nonparametric estimator slightly underestimated the rate and had slightly overconservative confidence intervals in some cases. Conversely, the parametric estimator overestimated the rate and had anticonservative confidence intervals in some cases. The nonparametric method appeared to be more robust to censoring than the parametric one. In conclusion, we recommend the nonparametric method, but the parametric method can be used as a supplementary tool.
Mots clés
Algorithms, Antineoplastic Agents, therapeutic use, Clinical Trials, Phase II as Topic, Colorectal Neoplasms, drug therapy, Computer Simulation, Data Collection, Data Interpretation, Statistical, Disease Progression, Humans, Medical Oncology, methods, Models, Statistical, Probability, Research Design, Treatment Outcome
Référence
Comput Math Methods Med. 2018 ;2018:1672176