title: Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project†.
abstract: BACKGROUND
  In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions.
  
  
  METHODS
  A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events.
  
  
  RESULTS
  Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression).
  
  
  CONCLUSIONS
  The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in all RCC clinical trials, thus facilitating reporting and increasing precision in between trial comparisons.
authors.affiliation: Methodology and Biostatistics Unit, Centre Oscar Lambret and SIRIC ONCO LILLE, Lille.
authors.forename: A
authors.initials: A
authors.lastname: Kramar
authors.affiliation: Department of Medical Oncology, University of Lyon I, Centre Léon Bérard, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Negrier
authors.affiliation: Department of Biostatistics, EORTC Headquarters, Brussels.
authors.forename: R
authors.initials: R
authors.lastname: Sylvester
authors.affiliation: Department of Urology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Joniau
authors.affiliation: Department of Urology, Radboud University Medical Centre, Nijmegan, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Mulders
authors.affiliation: Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Powles
authors.affiliation: Department of Urology, The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Bex
authors.affiliation: Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon.
authors.forename: F
authors.initials: F
authors.lastname: Bonnetain
authors.affiliation: Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Bossi
authors.affiliation: Department of Oncology, Ospedale San Donato, Arezzo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bracarda
authors.affiliation: Department of Immunology, Cleveland Clinic Taussig Cancer Center, Cleveland, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bukowski
authors.affiliation: Academic Urology Unit, University of Sheffield, Sheffield, UK.
authors.forename: J
authors.initials: J
authors.lastname: Catto
authors.affiliation: Kidney Cancer Center, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, USA.
authors.forename: T K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton.
authors.forename: S
authors.initials: S
authors.lastname: Crabb
authors.affiliation: Department of Oncology, Cambridge University Health Partners, Cambridge, UK.
authors.forename: T
authors.initials: T
authors.lastname: Eisen
authors.affiliation: Department of Medical Oncology, University Hospital of Nîmes, Nimes, France.
authors.forename: M
authors.initials: M
authors.lastname: El Demery
authors.affiliation: Division of Surgery, Mater Misericordiae Hospital and University College Dublin, Dublin, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: Fitzpatrick
authors.affiliation: Department of Urology, University Lille2 Nord de France, Lille, France.
authors.forename: V
authors.initials: V
authors.lastname: Flamand
authors.affiliation: Department of Urology, Friedrich-Alexander University Erlangen-Nueremberg, Erlangen, Germany.
authors.forename: P J
authors.initials: PJ
authors.lastname: Goebell
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, Marseille.
authors.forename: G
authors.initials: G
authors.lastname: Gravis
authors.affiliation: Department of Medical Oncology, CHU Caremeau, Nîmes.
authors.forename: N
authors.initials: N
authors.lastname: Houédé
authors.affiliation: Department of Urology, CHRU, Strasbourg, France.
authors.forename: D
authors.initials: D
authors.lastname: Jacqmin
authors.affiliation: MRC Clinical Trials Unit, University College London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Kaplan
authors.affiliation: Department of Urology, CHU, Toulouse, France.
authors.forename: B
authors.initials: B
authors.lastname: Malavaud
authors.affiliation: Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Massard
authors.affiliation: Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic.
authors.forename: B
authors.initials: B
authors.lastname: Melichar
authors.affiliation: Department of Medical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer-Oncopole, Toulouse, France.
authors.forename: L
authors.initials: L
authors.lastname: Mourey
authors.affiliation: Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, Middlesex, UK.
authors.forename: P
authors.initials: P
authors.lastname: Nathan
authors.affiliation: Department of Academic Radiation Oncology, Centre Oscar Lambret and SIRIC ONCO LILLE, Lille, France.
authors.forename: D
authors.initials: D
authors.lastname: Pasquier
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Porta
authors.affiliation: Department of Medical Oncology, Hôpital Saint-Louis, APHP, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Pouessel
authors.affiliation: Division of Oncology, USC Norris Comprehensive Cancer Center and Hospital, Los Angeles, USA.
authors.forename: D
authors.initials: D
authors.lastname: Quinn
authors.affiliation: Department of Medical Oncology, Hôpital Saint André, Bordeaux.
authors.forename: A
authors.initials: A
authors.lastname: Ravaud
authors.affiliation: Department of Medical Oncology, Institut de cancérologie de l'Ouest-René Gauducheau, Nantes, France.
authors.forename: F
authors.initials: F
authors.lastname: Rolland
authors.affiliation: Department of Medicine I, Clinical Division of Oncology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Schmidinger
authors.affiliation: Department of Urology, Cliniques Universitaires Saint Luc, Brussels, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Tombal
authors.affiliation: Department of Medical Oncology, Institut Régional du Cancer Val d'Aurelle, Montpellier.
authors.forename: D
authors.initials: D
authors.lastname: Tosi
authors.affiliation: Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
authors.forename: E
authors.initials: E
authors.lastname: Vauleon
authors.affiliation: Division of Urology, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Volpe
authors.affiliation: Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Wolter
authors.affiliation: Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: B
authors.initials: B
authors.lastname: Escudier
authors.affiliation: Department of Medical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer-Oncopole, Toulouse, France filleron.thomas@iuct-oncopole.fr.
authors.forename: T
authors.initials: T
authors.lastname: Filleron
mesh_terms: D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000628:therapy*; D003697:Delphi Technique; D018572:Disease-Free Survival; D023381:Endpoint Determination / Q000379:methods / Q000592:standards*; D019983:Guideline Adherence / Q000592:standards*; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000628:therapy; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards*
keywords: DATECAN; clinical trials; recommendations; renal cell cancer; time-to-event end points