title: Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European LeukemiaNet.
abstract: The treatment policy of chronic myeloid leukemia (CML), particularly with tyrosine kinase inhibitors, has been influenced by several recent studies that were well designed and rapidly performed, but their interpretation is of some concern because different end points and methodologies were used. To understand and compare the results of the previous and future studies and to translate their conclusion into clinical practice, there is a need for common definitions and methods for analyses of CML studies. A panel of experts was appointed by the European LeukemiaNet with the aim of developing a set of definitions and recommendations to be used in design, analyses, and reporting of phase 3 clinical trials in this disease. This paper summarizes the consensus of the panel on events and major end points of interest in CML. It also focuses on specific issues concerning the intention-to-treat principle and longitudinal data analyses in the context of long-term follow-up. The panel proposes that future clinical trials follow these recommendations.
authors.affiliation: INSERM CIC 0802, Centre Hospitalier Universitaire de Poitiers, 2 rue de la Milétrie, Poitiers, France. j.guilhot@chu-poitiers.fr
authors.forename: Joëlle
authors.initials: J
authors.lastname: Guilhot
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Richard E
authors.initials: RE
authors.lastname: Clark
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Sergei
authors.initials: S
authors.lastname: Kulikov
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Petzer
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Susanne
authors.initials: S
authors.lastname: Saussele
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
authors.forename: Juan-Luis
authors.initials: JL
authors.lastname: Steegmann
authors.forename: Andrey
authors.initials: A
authors.lastname: Zaritskey
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hehlmann
mesh_terms: D017326:Clinical Trials, Phase III as Topic / Q000379:methods* / Q000706:statistics & numerical data*; D019058:Community Networks / Q000458:organization & administration; D003627:Data Interpretation, Statistical; D018572:Disease-Free Survival; D023381:Endpoint Determination / Q000379:methods / Q000706:statistics & numerical data; D005060:Europe; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000453:epidemiology / Q000401:mortality / Q000628:therapy*; D008954:Models, Biological; D017410:Practice Guidelines as Topic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011788:Quality of Life; D012107:Research Design; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors