title: Novel dose-finding designs and considerations on practical implementations in oncology clinical trials.
abstract: One of the main objectives in phase I oncology trials is to evaluate safety and tolerability of an experimental treatment by estimating the maximum tolerated dose (MTD) based on the rate of dose-limiting toxicities (DLT). To meet emerging challenges in dose-finding studies, over the past two decades, extensive research has been conducted by statistical and medical researchers to create innovative dose finding designs that perform better than the standard 3 + 3 design, which often exhibits undesirable statistical and operational properties. However, clinical implementation and practical usage of these new designs have been limited. This article begins with a review of the most recent literature and then provides some perspectives on implementing novel adaptive dose finding designs in oncology phase I trials from a pharmaceutical industry perspective. Statistical planning and logistical considerations on how to effectively execute such designs in multi-center clinical trials are discussed using two recent case studies.
authors.affiliation: a Pfizer Oncology, Pfizer Inc. , Groton , Connecticut , USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.affiliation: b Pfizer Oncology, Pfizer Inc. , San Diego , California , USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Bycott
authors.affiliation: a Pfizer Oncology, Pfizer Inc. , Groton , Connecticut , USA.
authors.forename: Enayet
authors.initials: E
authors.lastname: Talukder
mesh_terms: D017321:Clinical Trials, Phase I as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020714:Maximum Tolerated Dose; D008495:Medical Oncology; D012107:Research Design
keywords: Adaptive design; MTD; dose finding; oncology; phase I