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Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points

Background: The correlation between efficacy end points in randomized controlled trials (RCTs) of systemic therapy for non-Hodgkin's lymphoma (NHL) was investigated to identify an appropriate surrogate end point for overall survival (OS). Methods: RCTs of previously untreated NHL published from...

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Autores principales: Lee, L., Wang, L., Crump, M.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101365/
https://www.ncbi.nlm.nih.gov/pubmed/21266519
http://dx.doi.org/10.1093/annonc/mdq615
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author Lee, L.
Wang, L.
Crump, M.
author_facet Lee, L.
Wang, L.
Crump, M.
author_sort Lee, L.
collection PubMed
description Background: The correlation between efficacy end points in randomized controlled trials (RCTs) of systemic therapy for non-Hodgkin's lymphoma (NHL) was investigated to identify an appropriate surrogate end point for overall survival (OS). Methods: RCTs of previously untreated NHL published from 1990 to 2009 were identified. Associations between absolute differences in efficacy end points were determined using nonparametric Spearman's rank correlation coefficients (r(s)). Results: Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included. For aggressive NHL, differences in 3-year progression-free survival (PFS)/event-free survival (EFS) were high correlated with differences in 5-year OS {r(s) of 0.90 [95% confidence interval (CI) 0.73–0.96]} and linear regression determined that a 10% improvement in 3-year EFS or PFS would predict for a 7% ± 1% improvement in 5-year OS. For indolent histology disease, differences in complete response were strongly correlated with differences in 3-year EFS [r(s) 0.86 (95% CI 0.35–0.97)], but there was no correlation between 3-year time-to-event end points and 5-year OS. Conclusions: Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a candidate surrogate end point. Definition of these relationships may inform future clinical trial design and interpretation of interim trial data.
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spelling pubmed-31013652011-05-26 Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points Lee, L. Wang, L. Crump, M. Ann Oncol Original Articles Background: The correlation between efficacy end points in randomized controlled trials (RCTs) of systemic therapy for non-Hodgkin's lymphoma (NHL) was investigated to identify an appropriate surrogate end point for overall survival (OS). Methods: RCTs of previously untreated NHL published from 1990 to 2009 were identified. Associations between absolute differences in efficacy end points were determined using nonparametric Spearman's rank correlation coefficients (r(s)). Results: Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included. For aggressive NHL, differences in 3-year progression-free survival (PFS)/event-free survival (EFS) were high correlated with differences in 5-year OS {r(s) of 0.90 [95% confidence interval (CI) 0.73–0.96]} and linear regression determined that a 10% improvement in 3-year EFS or PFS would predict for a 7% ± 1% improvement in 5-year OS. For indolent histology disease, differences in complete response were strongly correlated with differences in 3-year EFS [r(s) 0.86 (95% CI 0.35–0.97)], but there was no correlation between 3-year time-to-event end points and 5-year OS. Conclusions: Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a candidate surrogate end point. Definition of these relationships may inform future clinical trial design and interpretation of interim trial data. Oxford University Press 2011-06 2011-01-25 /pmc/articles/PMC3101365/ /pubmed/21266519 http://dx.doi.org/10.1093/annonc/mdq615 Text en © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Lee, L.
Wang, L.
Crump, M.
Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points
title Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points
title_full Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points
title_fullStr Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points
title_full_unstemmed Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points
title_short Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points
title_sort identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101365/
https://www.ncbi.nlm.nih.gov/pubmed/21266519
http://dx.doi.org/10.1093/annonc/mdq615
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