Cargando…

Probing the Effective Treatment Thresholds for Alteplase in Acute Ischemic Stroke With Regression Discontinuity Designs

Randomized Controlled Trials (RCTs) are considered the gold standard for measuring the efficacy of medical interventions. However, RCTs are expensive, and use a limited population. Techniques to estimate the effects of stroke interventions from observational data that minimize confounding would be u...

Descripción completa

Detalles Bibliográficos
Autores principales: Naidech, Andrew M., Lawlor, Patrick N., Xu, Haolin, Fonarow, Gregg C., Xian, Ying, Smith, Eric E., Schwamm, Lee, Matsouaka, Roland, Prabhakaran, Shyam, Marinescu, Ioana, Kording, Konrad P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492202/
https://www.ncbi.nlm.nih.gov/pubmed/32982952
http://dx.doi.org/10.3389/fneur.2020.00961
_version_ 1783582340705943552
author Naidech, Andrew M.
Lawlor, Patrick N.
Xu, Haolin
Fonarow, Gregg C.
Xian, Ying
Smith, Eric E.
Schwamm, Lee
Matsouaka, Roland
Prabhakaran, Shyam
Marinescu, Ioana
Kording, Konrad P.
author_facet Naidech, Andrew M.
Lawlor, Patrick N.
Xu, Haolin
Fonarow, Gregg C.
Xian, Ying
Smith, Eric E.
Schwamm, Lee
Matsouaka, Roland
Prabhakaran, Shyam
Marinescu, Ioana
Kording, Konrad P.
author_sort Naidech, Andrew M.
collection PubMed
description Randomized Controlled Trials (RCTs) are considered the gold standard for measuring the efficacy of medical interventions. However, RCTs are expensive, and use a limited population. Techniques to estimate the effects of stroke interventions from observational data that minimize confounding would be useful. We used regression discontinuity design (RDD), a technique well-established in economics, on the Get With The Guidelines-Stroke (GWTG-Stroke) data set. RDD, based on regression, measures the occurrence of a discontinuity in an outcome (e.g., odds of home discharge) as a function of an intervention (e.g., alteplase) that becomes significantly more likely when crossing the threshold of a continuous variable that determines that intervention (e.g., time from symptom onset, since alteplase is only given if symptom onset is less than e.g., 3 h). The technique assumes that patients near either side of a threshold (e.g., 2.99 and 3.01 h from symptom onset) are indistinguishable other than the use of the treatment. We compared outcomes of patients whose estimated onset to treatment time fell on either side of the treatment threshold for three cohorts of patients in the GWTG-Stroke data set. This data set spanned three different treatment thresholds for alteplase (3 h, 2003–2007, N = 1,869; 3 h, 2009–2016, N = 13,086, and 4.5 h, 2009–2016, N = 6,550). Patient demographic characteristics were overall similar across the treatment thresholds. We did not find evidence of a discontinuity in clinical outcome at any treatment threshold attributable to alteplase. Potential reasons for failing to find an effect include violation of some RDD assumptions in clinical care, large sample sizes required, or already-well-chosen treatment threshold.
format Online
Article
Text
id pubmed-7492202
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-74922022020-09-25 Probing the Effective Treatment Thresholds for Alteplase in Acute Ischemic Stroke With Regression Discontinuity Designs Naidech, Andrew M. Lawlor, Patrick N. Xu, Haolin Fonarow, Gregg C. Xian, Ying Smith, Eric E. Schwamm, Lee Matsouaka, Roland Prabhakaran, Shyam Marinescu, Ioana Kording, Konrad P. Front Neurol Neurology Randomized Controlled Trials (RCTs) are considered the gold standard for measuring the efficacy of medical interventions. However, RCTs are expensive, and use a limited population. Techniques to estimate the effects of stroke interventions from observational data that minimize confounding would be useful. We used regression discontinuity design (RDD), a technique well-established in economics, on the Get With The Guidelines-Stroke (GWTG-Stroke) data set. RDD, based on regression, measures the occurrence of a discontinuity in an outcome (e.g., odds of home discharge) as a function of an intervention (e.g., alteplase) that becomes significantly more likely when crossing the threshold of a continuous variable that determines that intervention (e.g., time from symptom onset, since alteplase is only given if symptom onset is less than e.g., 3 h). The technique assumes that patients near either side of a threshold (e.g., 2.99 and 3.01 h from symptom onset) are indistinguishable other than the use of the treatment. We compared outcomes of patients whose estimated onset to treatment time fell on either side of the treatment threshold for three cohorts of patients in the GWTG-Stroke data set. This data set spanned three different treatment thresholds for alteplase (3 h, 2003–2007, N = 1,869; 3 h, 2009–2016, N = 13,086, and 4.5 h, 2009–2016, N = 6,550). Patient demographic characteristics were overall similar across the treatment thresholds. We did not find evidence of a discontinuity in clinical outcome at any treatment threshold attributable to alteplase. Potential reasons for failing to find an effect include violation of some RDD assumptions in clinical care, large sample sizes required, or already-well-chosen treatment threshold. Frontiers Media S.A. 2020-09-02 /pmc/articles/PMC7492202/ /pubmed/32982952 http://dx.doi.org/10.3389/fneur.2020.00961 Text en Copyright © 2020 Naidech, Lawlor, Xu, Fonarow, Xian, Smith, Schwamm, Matsouaka, Prabhakaran, Marinescu and Kording. http://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 Neurology
Naidech, Andrew M.
Lawlor, Patrick N.
Xu, Haolin
Fonarow, Gregg C.
Xian, Ying
Smith, Eric E.
Schwamm, Lee
Matsouaka, Roland
Prabhakaran, Shyam
Marinescu, Ioana
Kording, Konrad P.
Probing the Effective Treatment Thresholds for Alteplase in Acute Ischemic Stroke With Regression Discontinuity Designs
title Probing the Effective Treatment Thresholds for Alteplase in Acute Ischemic Stroke With Regression Discontinuity Designs
title_full Probing the Effective Treatment Thresholds for Alteplase in Acute Ischemic Stroke With Regression Discontinuity Designs
title_fullStr Probing the Effective Treatment Thresholds for Alteplase in Acute Ischemic Stroke With Regression Discontinuity Designs
title_full_unstemmed Probing the Effective Treatment Thresholds for Alteplase in Acute Ischemic Stroke With Regression Discontinuity Designs
title_short Probing the Effective Treatment Thresholds for Alteplase in Acute Ischemic Stroke With Regression Discontinuity Designs
title_sort probing the effective treatment thresholds for alteplase in acute ischemic stroke with regression discontinuity designs
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492202/
https://www.ncbi.nlm.nih.gov/pubmed/32982952
http://dx.doi.org/10.3389/fneur.2020.00961
work_keys_str_mv AT naidechandrewm probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns
AT lawlorpatrickn probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns
AT xuhaolin probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns
AT fonarowgreggc probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns
AT xianying probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns
AT smitherice probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns
AT schwammlee probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns
AT matsouakaroland probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns
AT prabhakaranshyam probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns
AT marinescuioana probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns
AT kordingkonradp probingtheeffectivetreatmentthresholdsforalteplaseinacuteischemicstrokewithregressiondiscontinuitydesigns