Application of the target trial emulation framework to external comparator studies

External comparator (EC) studies are increasingly being used to generate evidence that supports the evaluation of emerging pharmacological treatments for regulatory and health technology assessment (HTA) purposes. However, the reliability of evidence generated from EC studies can vary. In this paper...

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Main Authors: Kellyn Arnold, Luis Antunes, Briana Coles, Hopin Lee
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-04-01
Series:Frontiers in Drug Safety and Regulation
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fdsfr.2024.1380568/full
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author Kellyn Arnold
Luis Antunes
Briana Coles
Hopin Lee
author_facet Kellyn Arnold
Luis Antunes
Briana Coles
Hopin Lee
author_sort Kellyn Arnold
collection DOAJ
description External comparator (EC) studies are increasingly being used to generate evidence that supports the evaluation of emerging pharmacological treatments for regulatory and health technology assessment (HTA) purposes. However, the reliability of evidence generated from EC studies can vary. In this paper, we outline how an existing framework for causal inference, the target trial emulation (TTE) framework, can be appropriately applied to improve the design and analysis of EC studies. Applying the TTE framework involves specifying the protocol of an ideal target trial which would answer the causal question of interest, then emulating its key elements under real-world (RW) settings. We describe each component of the original TTE framework and explain how it can be applied to EC studies, supplemented with practical recommendations. We also highlight special considerations and limitations in applying the TTE framework to EC studies. We describe how the TTE framework can be applied to improve the clarity, transparency, and reliability of evidence generated from EC studies.
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spelling doaj-art-c5221997af194e45a7af6e158cba3cb32025-08-20T01:53:27ZengFrontiers Media S.A.Frontiers in Drug Safety and Regulation2674-08692024-04-01410.3389/fdsfr.2024.13805681380568Application of the target trial emulation framework to external comparator studiesKellyn Arnold0Luis Antunes1Briana Coles2Hopin Lee3IQVIA, Methods and Evidence Generation, London, United KingdomIQVIA, Methods and Evidence Generation, Lisbon, PortugalIQVIA, Methods and Evidence Generation, London, United KingdomIQVIA, Methods and Evidence Generation, London, United KingdomExternal comparator (EC) studies are increasingly being used to generate evidence that supports the evaluation of emerging pharmacological treatments for regulatory and health technology assessment (HTA) purposes. However, the reliability of evidence generated from EC studies can vary. In this paper, we outline how an existing framework for causal inference, the target trial emulation (TTE) framework, can be appropriately applied to improve the design and analysis of EC studies. Applying the TTE framework involves specifying the protocol of an ideal target trial which would answer the causal question of interest, then emulating its key elements under real-world (RW) settings. We describe each component of the original TTE framework and explain how it can be applied to EC studies, supplemented with practical recommendations. We also highlight special considerations and limitations in applying the TTE framework to EC studies. We describe how the TTE framework can be applied to improve the clarity, transparency, and reliability of evidence generated from EC studies.https://www.frontiersin.org/articles/10.3389/fdsfr.2024.1380568/fullexternal comparatorexternal controltarget trial emulationcausal inferencecomparative effectivenesshealth technology assessment
spellingShingle Kellyn Arnold
Luis Antunes
Briana Coles
Hopin Lee
Application of the target trial emulation framework to external comparator studies
Frontiers in Drug Safety and Regulation
external comparator
external control
target trial emulation
causal inference
comparative effectiveness
health technology assessment
title Application of the target trial emulation framework to external comparator studies
title_full Application of the target trial emulation framework to external comparator studies
title_fullStr Application of the target trial emulation framework to external comparator studies
title_full_unstemmed Application of the target trial emulation framework to external comparator studies
title_short Application of the target trial emulation framework to external comparator studies
title_sort application of the target trial emulation framework to external comparator studies
topic external comparator
external control
target trial emulation
causal inference
comparative effectiveness
health technology assessment
url https://www.frontiersin.org/articles/10.3389/fdsfr.2024.1380568/full
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AT hopinlee applicationofthetargettrialemulationframeworktoexternalcomparatorstudies