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The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?

BACKGROUND: The clinical development of new drugs with radiation appears to be limited. We hypothesised that phase I clinical trials with radiation therapy (RT) are initiated too late into a new drug's lifetime, impeding the ability to complete RT–drug development programmes before patent expir...

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Autores principales: Blumenfeld, P, Pfeffer, R M, Symon, Z, Den, R B, Dicker, A P, Raben, D, Lawrence, Y R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183859/
https://www.ncbi.nlm.nih.gov/pubmed/25117813
http://dx.doi.org/10.1038/bjc.2014.448
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author Blumenfeld, P
Pfeffer, R M
Symon, Z
Den, R B
Dicker, A P
Raben, D
Lawrence, Y R
author_facet Blumenfeld, P
Pfeffer, R M
Symon, Z
Den, R B
Dicker, A P
Raben, D
Lawrence, Y R
author_sort Blumenfeld, P
collection PubMed
description BACKGROUND: The clinical development of new drugs with radiation appears to be limited. We hypothesised that phase I clinical trials with radiation therapy (RT) are initiated too late into a new drug's lifetime, impeding the ability to complete RT–drug development programmes before patent expiration. METHODS: We identified novel drug–radiation phase I combination trials performed between 1980 and 2012 within the PubMed and ClinicalTrials.gov databases. Data gathered for each drug included: date the initial phase I trial with/without RT was opened/published, date of the published positive phase III trials, and patent expiration dates. Lag time was defined as the interval between opening of the phase I trial without RT and the opening of the phase I with RT. Linear regression was used to model how the lag time has changed over time. RESULTS: The median lag time was 6 years. The initial phase I trial with RT was typically published 2 years after the first published positive phase III trial and 11 years before patent expiration. Using a best-fit linear model, lag time decreased from 10 years for phase I trials published in 1990 to 5 years in 2005 (slope significantly non-zero, P<0.001). CONCLUSIONS: Clinical drug development with RT commences late in the life cycle of anti-cancer agents. Taking into account the additional time required for late-phase clinical trials, the delay in initiating clinical testing of drug–RT combinations discourages drug companies from further pursuing RT-based development. Encouragingly, lag time appears to be decreasing. Further reduction in lag time may accelerate RT-based drug development, potentially improving patient outcomes.
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spelling pubmed-41838592015-09-23 The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress? Blumenfeld, P Pfeffer, R M Symon, Z Den, R B Dicker, A P Raben, D Lawrence, Y R Br J Cancer Clinical Study BACKGROUND: The clinical development of new drugs with radiation appears to be limited. We hypothesised that phase I clinical trials with radiation therapy (RT) are initiated too late into a new drug's lifetime, impeding the ability to complete RT–drug development programmes before patent expiration. METHODS: We identified novel drug–radiation phase I combination trials performed between 1980 and 2012 within the PubMed and ClinicalTrials.gov databases. Data gathered for each drug included: date the initial phase I trial with/without RT was opened/published, date of the published positive phase III trials, and patent expiration dates. Lag time was defined as the interval between opening of the phase I trial without RT and the opening of the phase I with RT. Linear regression was used to model how the lag time has changed over time. RESULTS: The median lag time was 6 years. The initial phase I trial with RT was typically published 2 years after the first published positive phase III trial and 11 years before patent expiration. Using a best-fit linear model, lag time decreased from 10 years for phase I trials published in 1990 to 5 years in 2005 (slope significantly non-zero, P<0.001). CONCLUSIONS: Clinical drug development with RT commences late in the life cycle of anti-cancer agents. Taking into account the additional time required for late-phase clinical trials, the delay in initiating clinical testing of drug–RT combinations discourages drug companies from further pursuing RT-based development. Encouragingly, lag time appears to be decreasing. Further reduction in lag time may accelerate RT-based drug development, potentially improving patient outcomes. Nature Publishing Group 2014-09-23 2014-08-12 /pmc/articles/PMC4183859/ /pubmed/25117813 http://dx.doi.org/10.1038/bjc.2014.448 Text en Copyright © 2014 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Clinical Study
Blumenfeld, P
Pfeffer, R M
Symon, Z
Den, R B
Dicker, A P
Raben, D
Lawrence, Y R
The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?
title The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?
title_full The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?
title_fullStr The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?
title_full_unstemmed The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?
title_short The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?
title_sort lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress?
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183859/
https://www.ncbi.nlm.nih.gov/pubmed/25117813
http://dx.doi.org/10.1038/bjc.2014.448
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