Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.
BACKGROUND
Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer.


METHODS
A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts.


RESULTS
Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings.


CONCLUSIONS
The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.
Biostatistic Unit, Montpellier Cancer Institute, Montpellier; Data Center for Cancer Clinical Trials, CTD-INCa, Montpellier, France. Electronic address: sophie.gourgou@icm.unicancer.fr.
S
S
Gourgou-Bourgade
Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital, Edinburgh, UK.
D
D
Cameron
Department of Radiation Oncology, Institute Verbeeten, Tilburg, The Netherlands.
P
P
Poortmans
Department of Biostatistics, Institut Curie, Paris.
B
B
Asselain
Department of Radiation Oncology, Montpellier Cancer Institute, Montpellier, France.
D
D
Azria
Breast Cancer Unit, Champalimaud Cancer Center, Lisbon, Portugal.
F
F
Cardoso
Institute of Cancer Research, London, UK.
R
R
A'Hern
Institute of Cancer Research, London, UK.
J
J
Bliss
EORTC Data Center (European Organization of Research and Treatment of Cancer - Statistics Department), Brussels, Belgium.
J
J
Bogaerts
Institut Bergonié, Comprehensive Cancer Centre, Bordeaux.
H
H
Bonnefoi
Departments of Clinical Research and Medical Oncology, Institut Curie - Hôpital René Huguenin, Saint-Cloud.
E
E
Brain
Breast Cancer Unit, Champalimaud Cancer Center, Lisbon, Portugal.
M J
MJ
Cardoso
Department of Medical Oncology, Hôpital Saint-Antoine, Paris, France.
B
B
Chibaudel
FRCP, FRCPE YCR National Institute for Health Research Cancer Research Network (NCRN), Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield Cancer Research Centre, Sheffield, UK.
R
R
Coleman
University Clinic Golnik, Golnik, Slovenia.
T
T
Cufer
Institut Jules Bordet, University 'Libre' of Brussels, Brussels, Belgium.
L
L
Dal Lago
Institut Claudius Régaud, Toulouse.
F
F
Dalenc
Institut Jules Bordet, University 'Libre' of Brussels, Brussels, Belgium.
E
E
De Azambuja
Institut Bergonié, Comprehensive Cancer Centre, Bordeaux.
M
M
Debled
Breast Cancer Group, Gustave Roussy Institute, Villejuif.
S
S
Delaloge
Institut Claudius Régaud, Toulouse.
T
T
Filleron
APHP Tenon - University Cancer Institute - Pierre & Marie Curie, Sorbonne University, Paris.
J
J
Gligorov
Department of Surgery.
M
M
Gutowski
Department of Medical Oncology, Montpellier Cancer Institute, Montpellier, France.
W
W
Jacot
Université catholique Louvain, Louvain-la-Neuve, Belgium.
C
C
Kirkove
Institut Bergonié, Comprehensive Cancer Centre, Bordeaux.
G
G
MacGrogan
Biostatistic and Epidemiology Unit, Gustave Roussy, Villejuif; University of Paris-Sud, Villejuif, France.
S
S
Michiels
Breast Unit, Hospital CUF Descobertas, Lisbon, Portugal.
I
I
Negreiros
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
B V
BV
Offersen
Centre Jean Perrin, Clermont-Ferrand; ERTICA EA4677, UFR Medicine, University of Clermont-Ferrand 1, Clermont-Ferrand, France.
F
F
Penault Llorca
European Institute of Oncology, Milan; University of Milan, School of Medicine, Milan, Italy.
G
G
Pruneri
Institut Claudius Régaud, Toulouse.
H
H
Roche
Department of Radiotherapy, The Netherlands Cancer Institute - Antoni van Leeuwnhoek Hospital, Amsterdam, The Netherlands.
N S
NS
Russell
IPATIMUP (Institute of Molecular Pathology and Immunology of the University of Porto), Porto; Medical Faculty of Porto University, Porto, Portugal.
F
F
Schmitt
Oscar Lambret Comprehensive Cancer Center, Lille, France.
V
V
Servent
Kantonsspital St Gallen, Breast Center, St Gallen, Switzerland.
B
B
Thürlimann
Clinic for Gynecology, Gynecologic Oncology and Obstetrics-Interdisciplinary Breast Cancer Center, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
M
M
Untch
Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam.
J A
JA
van der Hage
Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
G
G
van Tienhoven
Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven; Laboratory of Experimental Oncology (LEO), Department of Oncology, KU Leuven, Leuven, Belgium.
H
H
Wildiers
The Institute of Cancer Research, Royal Cancer Hospital, London, UK.
J
J
Yarnold
Methodological and Quality of Life Unit in Oncology (EA3181), CHU Besançon, Besançon.
F
F
Bonnetain
Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux; Clinical Epidemiology Unit, INSERM CIC 14.01 (Clinical Epidemiology), Bordeaux.
S
S
Mathoulin-Pélissier
Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux; Clinical Epidemiology Unit, INSERM CIC 14.01 (Clinical Epidemiology), Bordeaux.
C
C
Bellera
Biostatistics and Quality of Life Unit (EA4184), Centre Georges François Leclerc Comprehensive Cancer Centre, Dijon, France.
T S
TS
Dabakuyo-Yonli
D001943:Breast Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D032921:Consensus; D003697:Delphi Technique; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination / Q000145:classification / Q000592:standards*; D005260:Female; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000145:classification / Q000592:standards*; D012107:Research Design / Q000592:standards*; D009626:Terminology as Topic; D013997:Time Factors; D017211:Treatment Failure
breast cancer; efficacy measure; guidelines; randomized, controlled trial; time-to-event end point