An adaptive confirmatory trial with interim treatment selection: practical experiences and unbalanced randomization

التفاصيل البيبلوغرافية
العنوان: An adaptive confirmatory trial with interim treatment selection: practical experiences and unbalanced randomization
المؤلفون: Serigne Lo, Caroline C. Morgan, Stephane Heritier
المصدر: Statistics in medicine. 30(13)
سنة النشر: 2010
مصطلحات موضوعية: Statistics and Probability, Clinical Trials as Topic, Epidemiology, Interim analysis, Confirmatory trial, Closed testing procedure, Sample size determination, Research Design, Interim, Data Interpretation, Statistical, Covariate, Statistics, Test statistic, Humans, Computer Simulation, Monte Carlo Method, Mathematics, Type I and type II errors, Randomized Controlled Trials as Topic
الوصف: This article has been motivated by an ongoing international adaptive confirmatory trial. At the interim analysis of this two-stage trial, none, one or two active treatment regimens are selected for further study in the second stage. A combination test approach is used in this practical setting with an extension of the theory to unbalanced randomization. We show that a combination test with suitable weights can still preserve the overall Type I error rate provided that the test statistic is chosen appropriately and the unpooled Z-test for proportions is not used. The accuracy of stagewise p-values is also discussed in a more general framework. Monte Carlo simulations confirm the validity of the approach retained and evaluate the necessary sample size. Additional issues addressed during the design of the trial are also examined such as multiplicity due to testing hypotheses on key secondary endpoints, a non-inferiority comparison to an active treatment and covariate adjusted analyses for various types of outcome.
تدمد: 1097-0258
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::890b4d5d15ca4b5c6e0b10924ec7c08d
https://pubmed.ncbi.nlm.nih.gov/21432887
Rights: CLOSED
رقم الانضمام: edsair.doi.dedup.....890b4d5d15ca4b5c6e0b10924ec7c08d
قاعدة البيانات: OpenAIRE