@article{94da6c272e3c43ed8f62fb4326e329ba,
title = "Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines",
abstract = "Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines.",
keywords = "Dengue, Dengue vaccine, Enhancement, Vaccine clinical trials, Vaccine regulation",
author = "Vannice, {Kirsten S.} and Annelies Wilder-Smith and Barrett, {Alan D.T.} and Kalinka Carrijo and Marco Cavaleri and {de Silva}, Aravinda and Durbin, {Anna P.} and Tim Endy and Eva Harris and Innis, {Bruce L.} and Katzelnick, {Leah C.} and Smith, {Peter G.} and Wellington Sun and Thomas, {Stephen J.} and Joachim Hombach",
note = "Funding Information: The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the agencies or organizations with which the authors are affiliated. JH is a staff member of the World Health Organization, as was KV at the time of this work. AWS is consultant to the WHO on matters related to arboviral diseases. BI is an employee of PATH; he is a former employee of GSK. EH served on the Scientific Advisory Board of Sanofi Pasteur during the Phase 3 vaccine trials, and her laboratory received research funds from Takeda Vaccines, Inc. to analyze samples from vaccine recipients. PGS is a member of the Independent Data Monitoring Committee for trials of the CYD-TDV vaccine. APD has consulted with Merck & Co on dengue vaccines. ST serves on advisory and safety boards for Sanofi Pasteur and Takeda Vaccines, Inc., and has performed consulting work for GSK Vaccines and Merck & Co. ADS has consulted on dengue vaccines for Takeda, Merck and Glaxo Smith Kline. His group has received funding from Sanofi and Takeda to analyze vaccine induced immune responses. He is listed as an inventor on patents related to flavivirus vaccines and diagnostics. WS{\textquoteright}s contributions are informal communications and represent his best judgment. These comments do not bind or obligate the U.S. FDA. MC is a full time employee of the EMA. KC is a staff member of the Brazilian Health Regulatory Agency – Anvisa. The views and opinions here expressed should not be used in place of regulations, published guidance documents or direct discussions with Anvisa. Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2018",
month = jun,
day = "7",
doi = "10.1016/j.vaccine.2018.02.062",
language = "English (US)",
volume = "36",
pages = "3411--3417",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "24",
}