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Development of standard clinical endpoints for use in dengue interventional trials

Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine...

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Main Authors:	Tomashek, Kay M., Wills, Bridget, Lum, Lucy Chai See, Thomas, Laurent, Durbin, Anna, Leo, Yee-Sin, de Bosch, Norma, Rojas, Elsa, Hendrickx, Kim, Erpicum, Martin, Agulto, Liane, Jaenisch, Thomas, Tissera, Hasitha, Suntarattiwong, Piyarat, Collers, Beth Ann, Wallace, Derek, Schmidt, Alexander C., Precioso, Alexander, Narvaez, Federico, Thomas, Stephen J., Edelman, Robert, Siqueira, João Bosco, Cassetti, M. Cristina, Dempsey, Walla, Gubler, Duane J.
Format:	Article
Published:	Public Library of Science 2018
Subjects:	R Medicine
Online Access:	http://eprints.um.edu.my/20459/ https://doi.org/10.1371/journal.pntd.0006497
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spelling	my.um.eprints.204592019-02-25T02:04:34Z http://eprints.um.edu.my/20459/ Development of standard clinical endpoints for use in dengue interventional trials Tomashek, Kay M. Wills, Bridget Lum, Lucy Chai See Thomas, Laurent Durbin, Anna Leo, Yee-Sin de Bosch, Norma Rojas, Elsa Hendrickx, Kim Erpicum, Martin Agulto, Liane Jaenisch, Thomas Tissera, Hasitha Suntarattiwong, Piyarat Collers, Beth Ann Wallace, Derek Schmidt, Alexander C. Precioso, Alexander Narvaez, Federico Thomas, Stephen J. Edelman, Robert Siqueira, João Bosco Cassetti, M. Cristina Dempsey, Walla Gubler, Duane J. R Medicine Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials. Public Library of Science 2018 Article PeerReviewed Tomashek, Kay M. and Wills, Bridget and Lum, Lucy Chai See and Thomas, Laurent and Durbin, Anna and Leo, Yee-Sin and de Bosch, Norma and Rojas, Elsa and Hendrickx, Kim and Erpicum, Martin and Agulto, Liane and Jaenisch, Thomas and Tissera, Hasitha and Suntarattiwong, Piyarat and Collers, Beth Ann and Wallace, Derek and Schmidt, Alexander C. and Precioso, Alexander and Narvaez, Federico and Thomas, Stephen J. and Edelman, Robert and Siqueira, João Bosco and Cassetti, M. Cristina and Dempsey, Walla and Gubler, Duane J. (2018) Development of standard clinical endpoints for use in dengue interventional trials. PLoS Neglected Tropical Diseases, 12 (10). e0006497. ISSN 1935-2727 https://doi.org/10.1371/journal.pntd.0006497 doi:10.1371/journal.pntd.0006497
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine
spellingShingle	R Medicine Tomashek, Kay M. Wills, Bridget Lum, Lucy Chai See Thomas, Laurent Durbin, Anna Leo, Yee-Sin de Bosch, Norma Rojas, Elsa Hendrickx, Kim Erpicum, Martin Agulto, Liane Jaenisch, Thomas Tissera, Hasitha Suntarattiwong, Piyarat Collers, Beth Ann Wallace, Derek Schmidt, Alexander C. Precioso, Alexander Narvaez, Federico Thomas, Stephen J. Edelman, Robert Siqueira, João Bosco Cassetti, M. Cristina Dempsey, Walla Gubler, Duane J. Development of standard clinical endpoints for use in dengue interventional trials
description	Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.
format	Article
author	Tomashek, Kay M. Wills, Bridget Lum, Lucy Chai See Thomas, Laurent Durbin, Anna Leo, Yee-Sin de Bosch, Norma Rojas, Elsa Hendrickx, Kim Erpicum, Martin Agulto, Liane Jaenisch, Thomas Tissera, Hasitha Suntarattiwong, Piyarat Collers, Beth Ann Wallace, Derek Schmidt, Alexander C. Precioso, Alexander Narvaez, Federico Thomas, Stephen J. Edelman, Robert Siqueira, João Bosco Cassetti, M. Cristina Dempsey, Walla Gubler, Duane J.
author_facet	Tomashek, Kay M. Wills, Bridget Lum, Lucy Chai See Thomas, Laurent Durbin, Anna Leo, Yee-Sin de Bosch, Norma Rojas, Elsa Hendrickx, Kim Erpicum, Martin Agulto, Liane Jaenisch, Thomas Tissera, Hasitha Suntarattiwong, Piyarat Collers, Beth Ann Wallace, Derek Schmidt, Alexander C. Precioso, Alexander Narvaez, Federico Thomas, Stephen J. Edelman, Robert Siqueira, João Bosco Cassetti, M. Cristina Dempsey, Walla Gubler, Duane J.
author_sort	Tomashek, Kay M.
title	Development of standard clinical endpoints for use in dengue interventional trials
title_short	Development of standard clinical endpoints for use in dengue interventional trials
title_full	Development of standard clinical endpoints for use in dengue interventional trials
title_fullStr	Development of standard clinical endpoints for use in dengue interventional trials
title_full_unstemmed	Development of standard clinical endpoints for use in dengue interventional trials
title_sort	development of standard clinical endpoints for use in dengue interventional trials
publisher	Public Library of Science
publishDate	2018
url	http://eprints.um.edu.my/20459/ https://doi.org/10.1371/journal.pntd.0006497
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score	13.211869

Development of standard clinical endpoints for use in dengue interventional trials

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