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A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups. / Dodd, Lori E.; Follmann, Dean; Proschan, Michael; Wang, Jing; Malvy, Denis; van Griensven, Johan; Ciglenecki, Iza; Horby, Peter W.; Ansumana, Rashid; Jiang, Jia-Fu; Davey, Richard T.; Lane, H. Clifford; Gouel-Cheron, Aurelie.

In: Science Translational Medicine, Vol. 11, Nr. 520, 1049, 2019.

Onderzoeksoutput: Bijdrage aan tijdschriftA1: Web of Science-artikel

Harvard

Dodd, LE, Follmann, D, Proschan, M, Wang, J, Malvy, D, van Griensven, J, Ciglenecki, I, Horby, PW, Ansumana, R, Jiang, J-F, Davey, RT, Lane, HC & Gouel-Cheron, A 2019, 'A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups', Science Translational Medicine, vol. 11, nr. 520, 1049. https://doi.org/10.1126/scitranslmed.aaw1049

APA

Dodd, L. E., Follmann, D., Proschan, M., Wang, J., Malvy, D., van Griensven, J., ... Gouel-Cheron, A. (2019). A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups. Science Translational Medicine, 11(520), [1049]. https://doi.org/10.1126/scitranslmed.aaw1049

Vancouver

Author

Dodd, Lori E. ; Follmann, Dean ; Proschan, Michael ; Wang, Jing ; Malvy, Denis ; van Griensven, Johan ; Ciglenecki, Iza ; Horby, Peter W. ; Ansumana, Rashid ; Jiang, Jia-Fu ; Davey, Richard T. ; Lane, H. Clifford ; Gouel-Cheron, Aurelie. / A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups. In: Science Translational Medicine. 2019 ; Vol. 11, Nr. 520.

BibTeX

@article{dafa36ce476d461da46e998f588b2984,
title = "A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups",
abstract = "Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group, statistical modeling to create a control group could be a possibility. Such a model-based reference control would only be credible if it had the same mortality risk as that of the experimental group in the absence of treatment. One way to test this counterfactual assumption is to evaluate whether reasonable similarity exists across nonrandomized control groups from different clinical studies, which might suggest that a future control group would be similarly homogeneous. We evaluated similarity across six clinical studies conducted during the 2013-2016 West Africa outbreak of Ebola virus disease. These studies evaluated favipiravir, the biologic ZMapp, the antimalarial drug amodiaquine, or administration of convalescent plasma or convalescent whole blood. We compared the nonrandomized control groups of these six studies comprising 1147 individuals infected with Ebola virus. We found considerable heterogeneity, which did not disappear after statistical modeling to adjust for prognostic variables. Mortality risk varied widely (31 to 66{\%}) across the nonrandomized control arms of these six studies. Models adjusting for baseline covariates (age, sex, and cycle threshold, a proxy for viral load) failed to sufficiently recalibrate these studies and showed that heterogeneity remained. Our findings highlight concerns about making invalid conclusions when comparing nonrandomized control groups to cohorts receiving experimental treatments.",
keywords = "SIERRA-LEONE, SURVIVAL, TRIALS, MORTALITY, OUTCOMES, TIME",
author = "Dodd, {Lori E.} and Dean Follmann and Michael Proschan and Jing Wang and Denis Malvy and {van Griensven}, Johan and Iza Ciglenecki and Horby, {Peter W.} and Rashid Ansumana and Jia-Fu Jiang and Davey, {Richard T.} and Lane, {H. Clifford} and Aurelie Gouel-Cheron",
note = "CPDF",
year = "2019",
doi = "10.1126/scitranslmed.aaw1049",
language = "English",
volume = "11",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "AMER ASSOC ADVANCEMENT SCIENCE",
number = "520",

}

RIS

TY - JOUR

T1 - A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups

AU - Dodd, Lori E.

AU - Follmann, Dean

AU - Proschan, Michael

AU - Wang, Jing

AU - Malvy, Denis

AU - van Griensven, Johan

AU - Ciglenecki, Iza

AU - Horby, Peter W.

AU - Ansumana, Rashid

AU - Jiang, Jia-Fu

AU - Davey, Richard T.

AU - Lane, H. Clifford

AU - Gouel-Cheron, Aurelie

N1 - CPDF

PY - 2019

Y1 - 2019

N2 - Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group, statistical modeling to create a control group could be a possibility. Such a model-based reference control would only be credible if it had the same mortality risk as that of the experimental group in the absence of treatment. One way to test this counterfactual assumption is to evaluate whether reasonable similarity exists across nonrandomized control groups from different clinical studies, which might suggest that a future control group would be similarly homogeneous. We evaluated similarity across six clinical studies conducted during the 2013-2016 West Africa outbreak of Ebola virus disease. These studies evaluated favipiravir, the biologic ZMapp, the antimalarial drug amodiaquine, or administration of convalescent plasma or convalescent whole blood. We compared the nonrandomized control groups of these six studies comprising 1147 individuals infected with Ebola virus. We found considerable heterogeneity, which did not disappear after statistical modeling to adjust for prognostic variables. Mortality risk varied widely (31 to 66%) across the nonrandomized control arms of these six studies. Models adjusting for baseline covariates (age, sex, and cycle threshold, a proxy for viral load) failed to sufficiently recalibrate these studies and showed that heterogeneity remained. Our findings highlight concerns about making invalid conclusions when comparing nonrandomized control groups to cohorts receiving experimental treatments.

AB - Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group, statistical modeling to create a control group could be a possibility. Such a model-based reference control would only be credible if it had the same mortality risk as that of the experimental group in the absence of treatment. One way to test this counterfactual assumption is to evaluate whether reasonable similarity exists across nonrandomized control groups from different clinical studies, which might suggest that a future control group would be similarly homogeneous. We evaluated similarity across six clinical studies conducted during the 2013-2016 West Africa outbreak of Ebola virus disease. These studies evaluated favipiravir, the biologic ZMapp, the antimalarial drug amodiaquine, or administration of convalescent plasma or convalescent whole blood. We compared the nonrandomized control groups of these six studies comprising 1147 individuals infected with Ebola virus. We found considerable heterogeneity, which did not disappear after statistical modeling to adjust for prognostic variables. Mortality risk varied widely (31 to 66%) across the nonrandomized control arms of these six studies. Models adjusting for baseline covariates (age, sex, and cycle threshold, a proxy for viral load) failed to sufficiently recalibrate these studies and showed that heterogeneity remained. Our findings highlight concerns about making invalid conclusions when comparing nonrandomized control groups to cohorts receiving experimental treatments.

KW - SIERRA-LEONE

KW - SURVIVAL

KW - TRIALS

KW - MORTALITY

KW - OUTCOMES

KW - TIME

U2 - 10.1126/scitranslmed.aaw1049

DO - 10.1126/scitranslmed.aaw1049

M3 - A1: Web of Science-article

VL - 11

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 520

M1 - 1049

ER -

ID: 3135627