On the use of non-concurrent controls in platform trials: a scoping review

Background Platform trials gained popularity during the last few years as they increase flexibility compared to multi-arm trials by allowing new experimental arms entering when the trial already started. Using a shared control group in platform trials increases the trial efficiency compared to separ...

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Autores: Bofill Roig, Marta|||0000-0002-4400-7541, Burgwinkel, Cora, Garczarek, Ursula, Koenig, Frank, Posch, Martin, Nguyen, Quynh, Hees, Katharina
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/416515
Acceso en línea:https://hdl.handle.net/2117/416515
https://dx.doi.org/10.1186/s13063-023-07398-7
Access Level:acceso abierto
Palabra clave:External controls
Non-concurrent controls
Platform trials
Àrees temàtiques de la UPC::Matemàtiques i estadística::Estadística aplicada::Estadística biosanitària
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spelling On the use of non-concurrent controls in platform trials: a scoping reviewBofill Roig, Marta|||0000-0002-4400-7541Burgwinkel, CoraGarczarek, UrsulaKoenig, FrankPosch, MartinNguyen, QuynhHees, KatharinaExternal controlsNon-concurrent controlsPlatform trialsÀrees temàtiques de la UPC::Matemàtiques i estadística::Estadística aplicada::Estadística biosanitàriaBackground Platform trials gained popularity during the last few years as they increase flexibility compared to multi-arm trials by allowing new experimental arms entering when the trial already started. Using a shared control group in platform trials increases the trial efficiency compared to separate trials. Because of the later entry of some of the experimental treatment arms, the shared control group includes concurrent and non-concurrent control data. For a given experimental arm, non-concurrent controls refer to patients allocated to the control arm before the arm enters the trial, while concurrent controls refer to control patients that are randomised concurrently to the experimental arm. Using non-concurrent controls can result in bias in the estimate in case of time trends if the appropriate methodology is not used and the assumptions are not met. Methods We conducted two reviews on the use of non-concurrent controls in platform trials: one on statistical methodology and one on regulatory guidance. We broadened our searches to the use of external and historical control data. We conducted our review on the statistical methodology in 43 articles identified through a systematic search in PubMed and performed a review on regulatory guidance on the use of non-concurrent controls in 37 guidelines published on the EMA and FDA websites. Results Only 7/43 of the methodological articles and 4/37 guidelines focused on platform trials. With respect to the statistical methodology, in 28/43 articles, a Bayesian approach was used to incorporate external/non-concurrent controls while 7/43 used a frequentist approach and 8/43 considered both. The majority of the articles considered a method that downweights the non-concurrent control in favour of concurrent control data (34/43), using for instance meta-analytic or propensity score approaches, and 11/43 considered a modelling-based approach, using regression models to incorporate non-concurrent control data. In regulatory guidelines, the use of non-concurrent control data was considered critical but was deemed acceptable for rare diseases in 12/37 guidelines or was accepted in specific indications (12/37). Non-comparability (30/37) and bias (16/37) were raised most often as the general concerns with non-concurrent controls. Indication specific guidelines were found to be most instructive. Conclusions Statistical methods for incorporating non-concurrent controls are available in the literature, either by means of methods originally proposed for the incorporation of external controls or non-concurrent controls in platform trials. Methods mainly differ with respect to how the concurrent and non-concurrent data are combined and temporary changes handled. Regulatory guidance for non-concurrent controls in platform trials are currently still limited.Peer Reviewed20232023-06-1520242024-10-24journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/416515https://dx.doi.org/10.1186/s13063-023-07398-7reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/4165152026-05-27T15:37:01Z
dc.title.none.fl_str_mv On the use of non-concurrent controls in platform trials: a scoping review
title On the use of non-concurrent controls in platform trials: a scoping review
spellingShingle On the use of non-concurrent controls in platform trials: a scoping review
Bofill Roig, Marta|||0000-0002-4400-7541
External controls
Non-concurrent controls
Platform trials
Àrees temàtiques de la UPC::Matemàtiques i estadística::Estadística aplicada::Estadística biosanitària
title_short On the use of non-concurrent controls in platform trials: a scoping review
title_full On the use of non-concurrent controls in platform trials: a scoping review
title_fullStr On the use of non-concurrent controls in platform trials: a scoping review
title_full_unstemmed On the use of non-concurrent controls in platform trials: a scoping review
title_sort On the use of non-concurrent controls in platform trials: a scoping review
dc.creator.none.fl_str_mv Bofill Roig, Marta|||0000-0002-4400-7541
Burgwinkel, Cora
Garczarek, Ursula
Koenig, Frank
Posch, Martin
Nguyen, Quynh
Hees, Katharina
author Bofill Roig, Marta|||0000-0002-4400-7541
author_facet Bofill Roig, Marta|||0000-0002-4400-7541
Burgwinkel, Cora
Garczarek, Ursula
Koenig, Frank
Posch, Martin
Nguyen, Quynh
Hees, Katharina
author_role author
author2 Burgwinkel, Cora
Garczarek, Ursula
Koenig, Frank
Posch, Martin
Nguyen, Quynh
Hees, Katharina
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv External controls
Non-concurrent controls
Platform trials
Àrees temàtiques de la UPC::Matemàtiques i estadística::Estadística aplicada::Estadística biosanitària
topic External controls
Non-concurrent controls
Platform trials
Àrees temàtiques de la UPC::Matemàtiques i estadística::Estadística aplicada::Estadística biosanitària
description Background Platform trials gained popularity during the last few years as they increase flexibility compared to multi-arm trials by allowing new experimental arms entering when the trial already started. Using a shared control group in platform trials increases the trial efficiency compared to separate trials. Because of the later entry of some of the experimental treatment arms, the shared control group includes concurrent and non-concurrent control data. For a given experimental arm, non-concurrent controls refer to patients allocated to the control arm before the arm enters the trial, while concurrent controls refer to control patients that are randomised concurrently to the experimental arm. Using non-concurrent controls can result in bias in the estimate in case of time trends if the appropriate methodology is not used and the assumptions are not met. Methods We conducted two reviews on the use of non-concurrent controls in platform trials: one on statistical methodology and one on regulatory guidance. We broadened our searches to the use of external and historical control data. We conducted our review on the statistical methodology in 43 articles identified through a systematic search in PubMed and performed a review on regulatory guidance on the use of non-concurrent controls in 37 guidelines published on the EMA and FDA websites. Results Only 7/43 of the methodological articles and 4/37 guidelines focused on platform trials. With respect to the statistical methodology, in 28/43 articles, a Bayesian approach was used to incorporate external/non-concurrent controls while 7/43 used a frequentist approach and 8/43 considered both. The majority of the articles considered a method that downweights the non-concurrent control in favour of concurrent control data (34/43), using for instance meta-analytic or propensity score approaches, and 11/43 considered a modelling-based approach, using regression models to incorporate non-concurrent control data. In regulatory guidelines, the use of non-concurrent control data was considered critical but was deemed acceptable for rare diseases in 12/37 guidelines or was accepted in specific indications (12/37). Non-comparability (30/37) and bias (16/37) were raised most often as the general concerns with non-concurrent controls. Indication specific guidelines were found to be most instructive. Conclusions Statistical methods for incorporating non-concurrent controls are available in the literature, either by means of methods originally proposed for the incorporation of external controls or non-concurrent controls in platform trials. Methods mainly differ with respect to how the concurrent and non-concurrent data are combined and temporary changes handled. Regulatory guidance for non-concurrent controls in platform trials are currently still limited.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-06-15
2024
2024-10-24
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/416515
https://dx.doi.org/10.1186/s13063-023-07398-7
url https://hdl.handle.net/2117/416515
https://dx.doi.org/10.1186/s13063-023-07398-7
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
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