GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic.
BACKGROUND:Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty....
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ftdoajarticles:oai:doaj.org/article:3525208dd9394d07b5e2eed0dad3db55 2023-05-15T15:17:42+02:00 GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic. John Whitehead Peter Horby 2017-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005439 https://doaj.org/article/3525208dd9394d07b5e2eed0dad3db55 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5360336?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005439 https://doaj.org/article/3525208dd9394d07b5e2eed0dad3db55 PLoS Neglected Tropical Diseases, Vol 11, Iss 3, p e0005439 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005439 2022-12-31T10:18:07Z BACKGROUND:Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation. METHODOLOGY/PRINCIPAL FINDINGS:This paper proposes a generic ordinal sequential trial design (GOST) for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The design is intended as an off-the-shelf, ready-to-use robust and flexible option. The primary endpoint is a categorisation of patient outcome according to an ordinal scale. A sequential approach is adopted, stopping as soon as it is clear that the experimental treatment has an advantage or that sufficient advantage is unlikely to be detected. The properties of the design are evaluated using large-sample theory and verified for moderate sized samples using simulation. The trial is powered to detect a generic clinically relevant difference: namely an odds ratio of 2 for better rather than worse outcomes. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, but the precise value depends on both the magnitude of the treatment advantage and the nature of the ordinal scale. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size. CONCLUSIONS/SIGNIFICANCE:It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 3 e0005439 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 John Whitehead Peter Horby GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation. METHODOLOGY/PRINCIPAL FINDINGS:This paper proposes a generic ordinal sequential trial design (GOST) for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The design is intended as an off-the-shelf, ready-to-use robust and flexible option. The primary endpoint is a categorisation of patient outcome according to an ordinal scale. A sequential approach is adopted, stopping as soon as it is clear that the experimental treatment has an advantage or that sufficient advantage is unlikely to be detected. The properties of the design are evaluated using large-sample theory and verified for moderate sized samples using simulation. The trial is powered to detect a generic clinically relevant difference: namely an odds ratio of 2 for better rather than worse outcomes. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, but the precise value depends on both the magnitude of the treatment advantage and the nature of the ordinal scale. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size. CONCLUSIONS/SIGNIFICANCE:It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The ... |
format |
Article in Journal/Newspaper |
author |
John Whitehead Peter Horby |
author_facet |
John Whitehead Peter Horby |
author_sort |
John Whitehead |
title |
GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic. |
title_short |
GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic. |
title_full |
GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic. |
title_fullStr |
GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic. |
title_full_unstemmed |
GOST: A generic ordinal sequential trial design for a treatment trial in an emerging pandemic. |
title_sort |
gost: a generic ordinal sequential trial design for a treatment trial in an emerging pandemic. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005439 https://doaj.org/article/3525208dd9394d07b5e2eed0dad3db55 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 3, p e0005439 (2017) |
op_relation |
http://europepmc.org/articles/PMC5360336?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005439 https://doaj.org/article/3525208dd9394d07b5e2eed0dad3db55 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005439 |
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PLOS Neglected Tropical Diseases |
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11 |
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3 |
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e0005439 |
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