Development of standard clinical endpoints for use in dengue interventional trials

Kay M. Tomashek, Bridget Wills, Lucy Chai See Lum, Laurent Thomas, Anna P Durbin, Yee Sin Leo, Norma de Bosch, Elsa Rojas, Kim Hendrickx, Martin Erpicum, Liane Agulto, Thomas Jaenisch, Hasitha Tissera, Piyarat Suntarattiwong, Beth Ann Collers, Derek Wallace, Alexander C. Schmidt, Alexander Precioso, Federico Narvaez, Stephen J. ThomasRobert Edelman, João Bosco Siqueira, M. Cristina Cassetti, Walla Dempsey, Duane J. Gubler

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e0006497
JournalPLoS Neglected Tropical Diseases
Volume12
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Dengue
Thrombocytopenia
Dengue Vaccines
Public Health
Clinical Trials
Severe Dengue
Group Processes
Acute Liver Failure
Myocarditis
Nervous System Diseases
Platelet Count
Hepatitis
Consensus
Blood Platelets
Vaccines
Randomized Controlled Trials
Research Personnel
Hemorrhage
Safety
Mortality

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Tomashek, K. M., Wills, B., See Lum, L. C., Thomas, L., Durbin, A. P., Leo, Y. S., ... Gubler, D. J. (2018). Development of standard clinical endpoints for use in dengue interventional trials. PLoS Neglected Tropical Diseases, 12(10), e0006497. https://doi.org/10.1371/journal.pntd.0006497

Development of standard clinical endpoints for use in dengue interventional trials. / Tomashek, Kay M.; Wills, Bridget; See Lum, Lucy Chai; Thomas, Laurent; Durbin, Anna P; 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.

In: PLoS Neglected Tropical Diseases, Vol. 12, No. 10, 01.10.2018, p. e0006497.

Research output: Contribution to journalArticle

Tomashek, KM, Wills, B, See Lum, LC, Thomas, L, Durbin, AP, Leo, YS, de Bosch, N, Rojas, E, Hendrickx, K, Erpicum, M, Agulto, L, Jaenisch, T, Tissera, H, Suntarattiwong, P, Collers, BA, Wallace, D, Schmidt, AC, Precioso, A, Narvaez, F, Thomas, SJ, Edelman, R, Siqueira, JB, Cassetti, MC, Dempsey, W & Gubler, DJ 2018, 'Development of standard clinical endpoints for use in dengue interventional trials', PLoS Neglected Tropical Diseases, vol. 12, no. 10, pp. e0006497. https://doi.org/10.1371/journal.pntd.0006497
Tomashek, Kay M. ; Wills, Bridget ; See Lum, Lucy Chai ; Thomas, Laurent ; Durbin, Anna P ; 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. In: PLoS Neglected Tropical Diseases. 2018 ; Vol. 12, No. 10. pp. e0006497.
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