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Guidelines for the definition of time to event endpoints in renal cell cancer clinical trials: results of the DATECAN project

Guidelines for the definition of time to event endpoints in renal cell cancer clinical trials: results of the DATECAN project
Guidelines for the definition of time to event endpoints in renal cell cancer clinical trials: results of the DATECAN project
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.


Materials and 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.
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Catto, J.
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Kaplan, R.
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Malavaud, B.
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Melichar, B
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Mourey, L.
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Nathan, P.
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Pasquier, D.
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Porta, C.
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Pouessel, D.
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Sylvester, R.
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Joniau, S.
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Mulders, P.
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Powles, T.
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Bex, A.
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Bonnetain, F.
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Bossi, A.
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Bracarda, S.
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Bukowski, R.
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Catto, J.
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El Demery, M.
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Melichar, B
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Mourey, L.
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Nathan, P.
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Pasquier, D.
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Porta, C.
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Pouessel, D.
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Quinn, D.
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Ravaud, A.
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Rolland, F.
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Tombal, B.
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Tosi, D.
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Vauleon, E.
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Volpe, A.
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Wolter, P.
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Escudier, B.
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Kramar, A., Negrier, S., Sylvester, R., Joniau, S., Mulders, P., Powles, T., Bex, A., Bonnetain, F., Bossi, A., Bracarda, S., Bukowski, R., Catto, J., Choueiri, T.K., Crabb, S., Eisen, T., El Demery, M., Fitzpatrick, J., Flamand, V., Goebell, P.J., Gravis, G., Houédé, N., Jacqmin, D., Kaplan, R., Malavaud, B., Massard, C., Melichar, B, Mourey, L., Nathan, P., Pasquier, D., Porta, C., Pouessel, D., Quinn, D., Ravaud, A., Rolland, F., Schmidinger, M., Tombal, B., Tosi, D., Vauleon, E., Volpe, A., Wolter, P., Escudier, B. and Filleron, T. (2015) Guidelines for the definition of time to event endpoints in renal cell cancer clinical trials: results of the DATECAN project. Annals of Oncology, 26 (12), 2392-2398. (doi:10.1093/annonc/mdv380). (PMID:26371288)

Record type: Article

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.


Materials and 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.

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More information

Published date: 14 September 2015
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 381842
URI: http://eprints.soton.ac.uk/id/eprint/381842
ISSN: 1569-8041
PURE UUID: 07d94122-7f77-4e10-91a6-57b71b969273
ORCID for S. Crabb: ORCID iD orcid.org/0000-0003-3521-9064

Catalogue record

Date deposited: 16 Oct 2015 09:08
Last modified: 15 Mar 2024 03:16

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Contributors

Author: A. Kramar
Author: S. Negrier
Author: R. Sylvester
Author: S. Joniau
Author: P. Mulders
Author: T. Powles
Author: A. Bex
Author: F. Bonnetain
Author: A. Bossi
Author: S. Bracarda
Author: R. Bukowski
Author: J. Catto
Author: T.K. Choueiri
Author: S. Crabb ORCID iD
Author: T. Eisen
Author: M. El Demery
Author: J. Fitzpatrick
Author: V. Flamand
Author: P.J. Goebell
Author: G. Gravis
Author: N. Houédé
Author: D. Jacqmin
Author: R. Kaplan
Author: B. Malavaud
Author: C. Massard
Author: B Melichar
Author: L. Mourey
Author: P. Nathan
Author: D. Pasquier
Author: C. Porta
Author: D. Pouessel
Author: D. Quinn
Author: A. Ravaud
Author: F. Rolland
Author: M. Schmidinger
Author: B. Tombal
Author: D. Tosi
Author: E. Vauleon
Author: A. Volpe
Author: P. Wolter
Author: B. Escudier
Author: T. Filleron

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