Terms of Reference

The Working Group will be asked to review the evidence, identify the information gaps, and formulate proposed recommendations on the use of a licensed dengue vaccine for a SAGE review. This review is tentatively scheduled for April 2016. This will lead to the publication of a WHO position paper on the use of a dengue vaccine.

The Working Group will specifically be asked to review data relating to:

• the global prevalence and burden of disease caused by dengue
• the safety, efficacy, and immunogenicity profile of a licensed dengue vaccine
• the schedule, age of administration, and potential vaccination strategies for a dengue vaccine, including setting-specific attributes that may be important for designing immunization programs
• the disease impact and cost-effectiveness of dengue immunization programs
• identification of key data gaps that may be important for decisions about immunization programs, and recommendations for data collection related to key issues such as long-term safety, duration of protection, etc.
• additional critical issues that need to be considered in drafting proposed recommendations

Composition

SAGE members

• Terry Nolan, (Co-Chair of the Working Group), Melbourne School of Population and Global Health, Australia
• Piyanit Tharmaphornpilas, Ministry of Public Health, Thailand

Experts

• Jeremy Farrar, (Co-Chair of the Working Group), Wellcome Trust, UK
• Ananda Amarasinghe, Ministry of Health, Sri Lanka (resigned from Working Group 29 February 2016)
• Alan Barrett, University of Texas Medical Branch, USA
• Anna Durbin, Johns Hopkins Bloomberg School of Public Health, USA (resigned from Working Group 31 December 2015)
• Elizabeth Ferdinand, University of the West Indies, Barbados
• Maria Guzman, Pedro Kouri Tropical Medicine Institute, Cuba
• Maria Novaes, Universidade de São Paulo, Brazil
• Lee Ching Ng, National Environment Agency, Singapore
• Amadou Sall, Institut Pasteur de Dakar, Senegal
• Peter Smith, London School of Hygiene and Tropical Medicine, UK
• Wellington Sun, U.S. Food and Drug Administration, USA (resigned from Working Group 1 February 2016)
• Stephen Thomas, Walter Reed Army Institute of Research, USA

WHO secretariat

• Joachim Hombach
• Kirsten Vannice

Declaration of interests

All members completed a declaration of interests. Six members reported any relevant interests. It was concluded that all members could take part in full in all of the discussions. The reported relevant interests are summarized below:

Terence Nolan

• He received consultancy fees for participating in meetings and for data analysis and interpretation as member of Data and Safety Monitoring Board (DSMB) and Independent Data Monitoring Committee (IDMC) on Human Papilloma Virus vaccine from GSK. The consultancy was ceased by the 17th October 2012. This interest was assessed as personal, non-specific and financially significant*.
• In the time from 2008-2012 his institution received research support for vaccine trials implemented in Australia from a number of companies (including GSK, Wyeth, Novartis Vaccines, sanofi pasteur and CSL Ltd).These trials concern a number of vaccines (MenACWY, MenB, MenC, HibMenC Adult and peadiatric TIV, H1N1 and H5N1 vaccine and DTPa-Hib-hepB-IPV-MenC vaccine). This interest was assessed as non-personal, non-specific and financially significant*.
• His institution receives research support to conduct a follow-up clinical trial on a birthdose of Pertussis Vaccination from GSK. This interest was assessed as non-personal, non-specific and financially significant*.
• His institution receives research support to conduct a Meningococcal ACWY vaccine clinical trial from GSK. This interest was assessed as non-personal, non-specific and financially significant*.
• He serves as principal investigator for a clinical trial assessing the antibody response and persistence following MenACWY-TT funded by GSK and Murdoch Children's Research Institute. This interest was assessed as personal, non-specific and financially significant*.

Piyanit Tharmaphornpilas

• She received in 2011 a travel grant from a joint venture of the Thai Government Pharmaceutical Organization - Merieux Biological Product to attend the Re-invigorating Immunization Policy Implementation and Success: From Parent to Partner and from Broad to Engagement. This interest was assessed as personal, non-specific and financially significant*.

Alan Barrett

• His institution holds a contract funded by the U.S. National Institutes of Health to conduct a phase I clinical trial of the Takeda dengue vaccine candidate. This interest was assessed as non-personal, specific, and financially significant*.
• His institution participates in collaborative projects with Hawaii Biotech/Merck, two of which study recombinant flavivirus immunogens (tick-borne encephalitis). This interest was assessed as non-personal, non-specific, and financially significant*.
• He is co-investigator of a contract funded by the U.S. National Institutes of Health to test dengue drugs and vaccines in mouse models. This interest was assessed as personal, specific, and financially significant*.

Anna Durbin (resigned from Working Group in December 2015)

• She is co-investigator of a contract funded by the U.S. National Institutes of Health to test flavivirus vaccines, including the U.S. National Institutes of Health dengue vaccine candidate, in clinical trials. This interest was assessed as personal, specific, and financially significant*.
• She has provided expertise to Vabiotech and the Instituto Butantuan in relation to the U.S. National Institutes of Health dengue vaccine, funded by the German Federal Ministry of Education and Research (BMBF) through a grant to the Dengue Vaccine Initiative. This interest was assessed as personal, specific, and financially significant*.

Wellington Sun (resigned from Working Group 1 February 2016)

• He is a co-inventor of one U.S. patent (#6638514) for WRAIR's live attenuated dengue vaccine, which is no longer being developed commercially, and co-inventor on another EU patent (#2462930) for the strategy of prime-boost in dengue vaccines. This interest was assessed as personal, specific, and financially insignificant*.

Stephen Thomas

• His institution, the U.S. Army, has cooperative agreements with Sanofi Pasteur, GSK, and Takeda guiding the co-development of dengue vaccine development activities, that may include in kind financial support for travel or other support provided to the US Army. This interest was assessed as non-personal, specific, and financially significant*.

Peter Smith

• He is a member of the Independent Data Monitoring Committee for Sanofi Pasteur’s dengue vaccine clinical trials. This interest was assessed as personal, specific, and financially significant*.

* According to WHO's Guidelines for Declaration of Interests (WHO expert), an interest is considered "personal" if it generates financial or non-financial gain to the expert, such as consulting income or a patent. "Specificity" states whether the declared interest is a subject matter of the meeting or work to be undertaken. An interest has "financial significance" if the honoraria, consultancy fee or other received funding, including those received by expert's organization, from any single vaccine manufacturer or other vaccine-related company exceeds 5,000 USD in a calendar year. Likewise, a shareholding in any one vaccine manufacturer or other vaccine-related company in excess of 1,000 USD would also constitute a “significant shareholding”.