Potential impact of dengue vaccination: Insights from two large-scale phase III trials with a tetravalent dengue vaccine

This study defined the genetic epidemiology of dengue viruses (DENV) in two pivotal phase III trials of the tetravalent dengue vaccine, CYD-TDV, and thereby enabled virus genotype-specific estimates of vaccine efficacy (VE). Envelope gene sequences (n = 661) from 11 DENV genotypes in 10 endemic countries provided a contemporaneous global snapshot of DENV population genetics and revealed high amino acid identity between the E genes of vaccine strains and wild-type viruses from trial participants, including at epitope sites targeted by virus neutralising human monoclonal antibodies. Post-hoc analysis of all CYD14/15 trial participants revealed a statistically significant genotype-level VE association within DENV-4, where efficacy was lowest against genotype I. In subgroup analysis of trial participants age 9–16 years, VE estimates appeared more balanced within each serotype, suggesting that genotype-level heterogeneity may be limited in older children. Post-licensure surveillance is needed to monitor vaccine performance against the backdrop of DENV sequence diversity and evolution.

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Current Vaccine Trials in Glioblastoma: A Review

Journal of Immunology Research ◽

10.1155/2014/796856 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 32

Author(s):

Linda W. Xu ◽

Kevin K. H. Chow ◽

Michael Lim ◽

Gordon Li

Keyword(s):

Immune Responses ◽

Primary Brain Tumor ◽

Phase Iii ◽

Tumor Vaccines ◽

Vaccine Trials ◽

Average Survival ◽

Current Vaccine ◽

Phase Iii Trials ◽

Future Care ◽

Potential Impact

Glioblastoma (GBM) is the most common primary brain tumor, and despite aggressive therapy with surgery, radiation, and chemotherapy, average survival remains at about 1.5 years. The highly infiltrative and invasive nature of GBM requires that alternative treatments for this disease be widespread and targeted to tumor cells. Immunotherapy in the form of tumor vaccines has the potential to meet this need. Vaccines against GBM hold the promise of triggering specific and systemic antitumor immune responses that may be the key to eradicating this unrelenting cancer. In this review, we will discuss past and present clinical trials of various GBM vaccines and their potential impact on the future care of GBM patients. There have been many promising phase I and phase II GBM vaccine studies that have led to ongoing and upcoming phase III trials. If the results of these randomized trials show a survival benefit, immunotherapy will become a standard part of the treatment of this devastating disease.

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Author response: Genetic epidemiology of dengue viruses in phase III trials of the CYD tetravalent dengue vaccine and implications for efficacy

10.7554/elife.24196.056 ◽

2017 ◽

Cited By ~ 1

Author(s):

Maia A Rabaa ◽

Yves Girerd-Chambaz ◽

Kien Duong Thi Hue ◽

Trung Vu Tuan ◽

Bridget Wills ◽

...

Keyword(s):

Genetic Epidemiology ◽

Phase Iii ◽

Author Response ◽

Dengue Vaccine ◽

Dengue Viruses ◽

Phase Iii Trials

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The IGNITE Trial: Participant Recruitment Lessons Prior to SARS-CoV-2

10.1101/2020.05.19.20107458 ◽

2020 ◽

Author(s):

Eric D. Vidoni ◽

Amanda Szabo-Reed ◽

Chaeryon Kang ◽

Jaime Perales-Puchalt ◽

Ashley R. Shaw ◽

...

Keyword(s):

Large Scale ◽

The United States ◽

Phase Iii ◽

Trial Participant ◽

The Novel ◽

Brain Health ◽

Challenges And Opportunities ◽

Phase Iii Trials ◽

The Face ◽

Comprehensive Test

AbstractFull and diverse participant enrollment is critical to the success and generalizability of all large-scale Phase III trials. Recruitment of sufficient participants is among the most significant challenges for many studies. The novel SARS-CoV-2 coronavirus pandemic has further changed and challenged the landscape for clinical trial execution, including screening and randomization. The Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) study has been designed as the most comprehensive test of aerobic exercise effects on cognition and brain health. Here we assess recruitment into IGNITE prior to the increased infection rates in the United States, and examine new challenges and opportunities for recruitment with a goal of informing the remaining required recruitment as infection containment procedures are lifted. The results may assist the design and implementation of recruitment for future exercise studies, and outline opportunities for study design that are flexible in the face of emerging threats.

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Interval and point estimation in adaptive Phase II trials with binary endpoint

Statistical Methods in Medical Research ◽

10.1177/0962280218781411 ◽

2018 ◽

Vol 28 (9) ◽

pp. 2635-2648 ◽

Cited By ~ 1

Author(s):

Arsénio Nhacolo ◽

Werner Brannath

Keyword(s):

Phase Ii ◽

Large Scale ◽

Interval Estimation ◽

Point Estimation ◽

Phase Iii ◽

Phase Ii Trials ◽

Sequential Designs ◽

Group Sequential ◽

Fixed Sample ◽

Phase Iii Trials

Phase II clinical trials are concerned with making decision of whether a treatment is sufficiently efficacious to be worth further investigations in late large scale Phase III trials. In oncology Phase II trials, frequentist single-arm two-stage group-sequential designs with a binary endpoint are commonly used. To allow for more flexibility, adaptive versions of these designs have been proposed. In this paper, we propose point and interval estimation for adaptive designs in which the second stage sample size is a pre-specified function of first stage’s number of responses. Our approach is based on sample space orderings, from which we derive p-values, and point and interval estimates. Simulation studies show that our proposed methods perform better, in terms of bias and root mean square error, than the fixed-sample maximum likelihood estimator.

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