Cargando…

External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations

Randomized controlled trials are considered the ‘gold standard’ to reduce bias by randomizing patients to an experimental intervention, versus placebo or standard of care cohort. There are inherent challenges to enrolling a standard of care or cohorts: costs, site engagement logistics, socioeconomic...

Descripción completa

Detalles Bibliográficos
Autores principales: Silva, Patrick, Janjan, Nora, Ramos, Kenneth S., Udeani, George, Zhong, Lixian, Ory, Marcia G., Smith, Matthew Lee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359981/
https://www.ncbi.nlm.nih.gov/pubmed/37484840
http://dx.doi.org/10.3389/fmed.2023.1198088
_version_ 1785076004270637056
author Silva, Patrick
Janjan, Nora
Ramos, Kenneth S.
Udeani, George
Zhong, Lixian
Ory, Marcia G.
Smith, Matthew Lee
author_facet Silva, Patrick
Janjan, Nora
Ramos, Kenneth S.
Udeani, George
Zhong, Lixian
Ory, Marcia G.
Smith, Matthew Lee
author_sort Silva, Patrick
collection PubMed
description Randomized controlled trials are considered the ‘gold standard’ to reduce bias by randomizing patients to an experimental intervention, versus placebo or standard of care cohort. There are inherent challenges to enrolling a standard of care or cohorts: costs, site engagement logistics, socioeconomic variability, patient willingness, ethics of placebo interventions, cannibalizing the treatment arm population, and extending study duration. The COVID-19 pandemic has magnified aspects of constraints in trial recruitment and logistics, spurring innovative approaches to reducing trial sizes, accelerating trial accrual while preserving statistical rigor. Using data from medical records and databases allows for construction of external control arms that reduce the costs of an external control arm (ECA) randomized to standard of care. Simultaneously examining covariates of the clinical outcomes in ECAs that are being measured in the interventional arm can be particularly useful in phase 2 trials to better understand social and genetic determinants of clinical outcomes that might inform pivotal trial design. The FDA and EMA have promulgated a number of publicly available guidance documents and qualification reports that inform the use of this regulatory science tool to streamline clinical development, of phase 4 surveillance, and policy aspects of clinical outcomes research. Availability and quality of real-world data (RWD) are a prevalent impediment to the use of ECAs given such data is not collected with the rigor and deliberateness that characterizes prospective interventional control arm data. Conversely, in the case of contemporary control arms, a clinical trial outcome can be compared to a contemporary standard of care in cases where the standard of care is evolving at a fast pace, such as the use of checkpoint inhibitors in cancer care. Innovative statistical methods are an essential aspect of an ECA strategy and regulatory paths for these innovative approaches have been navigated, qualified, and in some cases published.
format Online
Article
Text
id pubmed-10359981
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-103599812023-07-22 External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations Silva, Patrick Janjan, Nora Ramos, Kenneth S. Udeani, George Zhong, Lixian Ory, Marcia G. Smith, Matthew Lee Front Med (Lausanne) Medicine Randomized controlled trials are considered the ‘gold standard’ to reduce bias by randomizing patients to an experimental intervention, versus placebo or standard of care cohort. There are inherent challenges to enrolling a standard of care or cohorts: costs, site engagement logistics, socioeconomic variability, patient willingness, ethics of placebo interventions, cannibalizing the treatment arm population, and extending study duration. The COVID-19 pandemic has magnified aspects of constraints in trial recruitment and logistics, spurring innovative approaches to reducing trial sizes, accelerating trial accrual while preserving statistical rigor. Using data from medical records and databases allows for construction of external control arms that reduce the costs of an external control arm (ECA) randomized to standard of care. Simultaneously examining covariates of the clinical outcomes in ECAs that are being measured in the interventional arm can be particularly useful in phase 2 trials to better understand social and genetic determinants of clinical outcomes that might inform pivotal trial design. The FDA and EMA have promulgated a number of publicly available guidance documents and qualification reports that inform the use of this regulatory science tool to streamline clinical development, of phase 4 surveillance, and policy aspects of clinical outcomes research. Availability and quality of real-world data (RWD) are a prevalent impediment to the use of ECAs given such data is not collected with the rigor and deliberateness that characterizes prospective interventional control arm data. Conversely, in the case of contemporary control arms, a clinical trial outcome can be compared to a contemporary standard of care in cases where the standard of care is evolving at a fast pace, such as the use of checkpoint inhibitors in cancer care. Innovative statistical methods are an essential aspect of an ECA strategy and regulatory paths for these innovative approaches have been navigated, qualified, and in some cases published. Frontiers Media S.A. 2023-07-06 /pmc/articles/PMC10359981/ /pubmed/37484840 http://dx.doi.org/10.3389/fmed.2023.1198088 Text en Copyright © 2023 Silva, Janjan, Ramos, Udeani, Zhong, Ory and Smith. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Silva, Patrick
Janjan, Nora
Ramos, Kenneth S.
Udeani, George
Zhong, Lixian
Ory, Marcia G.
Smith, Matthew Lee
External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations
title External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations
title_full External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations
title_fullStr External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations
title_full_unstemmed External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations
title_short External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations
title_sort external control arms: covid-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359981/
https://www.ncbi.nlm.nih.gov/pubmed/37484840
http://dx.doi.org/10.3389/fmed.2023.1198088
work_keys_str_mv AT silvapatrick externalcontrolarmscovid19revealsthemeritsofusingrealworldevidenceinrealtimeforclinicalandpublichealthinvestigations
AT janjannora externalcontrolarmscovid19revealsthemeritsofusingrealworldevidenceinrealtimeforclinicalandpublichealthinvestigations
AT ramoskenneths externalcontrolarmscovid19revealsthemeritsofusingrealworldevidenceinrealtimeforclinicalandpublichealthinvestigations
AT udeanigeorge externalcontrolarmscovid19revealsthemeritsofusingrealworldevidenceinrealtimeforclinicalandpublichealthinvestigations
AT zhonglixian externalcontrolarmscovid19revealsthemeritsofusingrealworldevidenceinrealtimeforclinicalandpublichealthinvestigations
AT orymarciag externalcontrolarmscovid19revealsthemeritsofusingrealworldevidenceinrealtimeforclinicalandpublichealthinvestigations
AT smithmatthewlee externalcontrolarmscovid19revealsthemeritsofusingrealworldevidenceinrealtimeforclinicalandpublichealthinvestigations