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What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020)
OBJECTIVE: To examine factors associated with accrual rate in industry sponsored clinical trials supporting US Food and Drug Administration (FDA) cancer drug approvals from 2015 to 2020. DESIGN, SETTING AND PARTICIPANTS: Retrospective cross-sectional study included 194 pivotal trials supporting canc...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BMJ Publishing Group
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558788/ https://www.ncbi.nlm.nih.gov/pubmed/36207035 http://dx.doi.org/10.1136/bmjopen-2022-064458 |
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author | Jenei, Kristina Haslam, Alyson Olivier, Timothée Miljkovíc, Milos Prasad, Vinay |
author_facet | Jenei, Kristina Haslam, Alyson Olivier, Timothée Miljkovíc, Milos Prasad, Vinay |
author_sort | Jenei, Kristina |
collection | PubMed |
description | OBJECTIVE: To examine factors associated with accrual rate in industry sponsored clinical trials supporting US Food and Drug Administration (FDA) cancer drug approvals from 2015 to 2020. DESIGN, SETTING AND PARTICIPANTS: Retrospective cross-sectional study included 194 pivotal trials supporting cancer drug approvals by the US FDA from 2015 to 2020. INTERVENTIONS: Clinical trials were analysed for the type of blinding, primary endpoint, whether crossover was specified in the publication, study phase, line of therapy, response rate, investigational sites, manufacturer and randomisation ratio. MAIN OUTCOME MEASURES: The main outcome was the rate of accrual, which is the number of patients accrued in the study per open month of enrolment. RESULTS: The study consisted of 133 randomised (68%) and 61 (32%) non-randomised clinical trials. In randomised studies, we found the accrual rate was higher in trials investigating first and second line drugs (adjusted rate ratios (aRR): 1.55, 95% CI 1.18 to 2.09), phase III trials (aRR: 2.13, 95% CI 1.48 to 2.99), and for studies sponsored by Merck (aRR: 1.47, 95% CI 1.18 to 2.37), adjusting for other covariates. In contrast, the primary endpoint of a study, presence of crossover, single agent response rate, the number of investigational sites, population disease burden and skewed randomisation ratios were not associated with the rate of accrual. In the non-randomised adjusted model, the accrual rate was 2.03 higher (95% CI 1.10 to 3.92) for clinical trials sponsored by manufacturer, specifically Merck. Primary endpoint, crossover, trial phase, response rate, the number of investigational sites, disease burden or line of therapy were not associated with the rate of accrual. CONCLUSION: In this cross-sectional study, line of therapy, study phase and manufacturer were the only factors associated with accrual rate. These findings suggest many proffered factors for speedy trial accrual are not associated with greater enrolment rates. |
format | Online Article Text |
id | pubmed-9558788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-95587882022-10-14 What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020) Jenei, Kristina Haslam, Alyson Olivier, Timothée Miljkovíc, Milos Prasad, Vinay BMJ Open Oncology OBJECTIVE: To examine factors associated with accrual rate in industry sponsored clinical trials supporting US Food and Drug Administration (FDA) cancer drug approvals from 2015 to 2020. DESIGN, SETTING AND PARTICIPANTS: Retrospective cross-sectional study included 194 pivotal trials supporting cancer drug approvals by the US FDA from 2015 to 2020. INTERVENTIONS: Clinical trials were analysed for the type of blinding, primary endpoint, whether crossover was specified in the publication, study phase, line of therapy, response rate, investigational sites, manufacturer and randomisation ratio. MAIN OUTCOME MEASURES: The main outcome was the rate of accrual, which is the number of patients accrued in the study per open month of enrolment. RESULTS: The study consisted of 133 randomised (68%) and 61 (32%) non-randomised clinical trials. In randomised studies, we found the accrual rate was higher in trials investigating first and second line drugs (adjusted rate ratios (aRR): 1.55, 95% CI 1.18 to 2.09), phase III trials (aRR: 2.13, 95% CI 1.48 to 2.99), and for studies sponsored by Merck (aRR: 1.47, 95% CI 1.18 to 2.37), adjusting for other covariates. In contrast, the primary endpoint of a study, presence of crossover, single agent response rate, the number of investigational sites, population disease burden and skewed randomisation ratios were not associated with the rate of accrual. In the non-randomised adjusted model, the accrual rate was 2.03 higher (95% CI 1.10 to 3.92) for clinical trials sponsored by manufacturer, specifically Merck. Primary endpoint, crossover, trial phase, response rate, the number of investigational sites, disease burden or line of therapy were not associated with the rate of accrual. CONCLUSION: In this cross-sectional study, line of therapy, study phase and manufacturer were the only factors associated with accrual rate. These findings suggest many proffered factors for speedy trial accrual are not associated with greater enrolment rates. BMJ Publishing Group 2022-10-07 /pmc/articles/PMC9558788/ /pubmed/36207035 http://dx.doi.org/10.1136/bmjopen-2022-064458 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Oncology Jenei, Kristina Haslam, Alyson Olivier, Timothée Miljkovíc, Milos Prasad, Vinay What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020) |
title | What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020) |
title_full | What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020) |
title_fullStr | What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020) |
title_full_unstemmed | What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020) |
title_short | What drives cancer clinical trial accrual? An empirical analysis of studies leading to FDA authorisation (2015–2020) |
title_sort | what drives cancer clinical trial accrual? an empirical analysis of studies leading to fda authorisation (2015–2020) |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558788/ https://www.ncbi.nlm.nih.gov/pubmed/36207035 http://dx.doi.org/10.1136/bmjopen-2022-064458 |
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