# Design and Analysis of Vaccine Trials for Emerging Infectious Disease Threats

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $712,070

## Abstract

ABSTRACT
Outbreaks of emerging pathogens have become more frequent, and we will likely face future epidemics for
which we are not adequately prepared. Effective vaccines are a critical tool for controlling infectious disease
threats, but experimental products must be rigorously evaluated for efficacy and safety before they can be
licensed and deployed. Our experience with the 2013-2016 West African Ebola epidemic highlighted the
unique challenges of conducting phase III vaccine efficacy trials for emerging pathogens. Besides issues of
strained infrastructure in typically resource-limited settings, incidence may be highly heterogeneous in the
population and spatiotemporally hard to predict. The outbreak may end before enough cases have accrued to
establish efficacy, as occurred in two of the three phase III Ebola vaccine trials. Compared to standard vaccine
clinical trials, researchers conducting trials during public health emergencies also generally have less
information about the disease and/or vaccine.
We supported the design and analysis of a third phase III Ebola vaccine trial in Guinea that used a novel ring
vaccination approach. Modeled after the strategy used to eradicate smallpox, clusters were defined as the
contacts and contacts of contacts of laboratory-confirmed Ebola virus disease cases and then cluster-
randomized to immediate or delayed vaccination. This trial demonstrated high efficacy of the candidate
vaccine, and its success was in part attributed to its innovative, responsive strategy that tracked the epidemic
as it progressed, precisely targeting individuals at highest risk of exposure. These experiences have motivated
an international call for novel methods for vaccine trial design and analysis adapted for emerging infectious
disease threats.
We propose the development of flexible, adaptive trial design strategies intended to increase the efficiency and
likelihood of success when evaluating experimental vaccines in outbreak settings. Our first aim is to develop a
class of responsive designs and associated tools for sample size calculation and analysis generalized beyond
ring vaccination. Our second aim is to outline strategies for implementing trials in outbreaks of unpredictable
duration, including how to define data monitoring rules and how to aggregate information across outbreaks
when any given outbreak is too small to support a trial. Our third aim is to design adaptive, multi-arm vaccine
trials with or without a control comparator. For each aim, we will describe the designs and the relevant
qualitative considerations, develop and validate the supporting statistical methods, and evaluate their
robustness using realistic, mathematical and computational disease transmission models. Our research
represents a critical first step for evaluating these strategies before they could be implemented in the field.

## Key facts

- **NIH application ID:** 10247049
- **Project number:** 7R01AI139761-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Natalie Exner Dean
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $712,070
- **Award type:** 7
- **Project period:** 2018-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247049

## Citation

> US National Institutes of Health, RePORTER application 10247049, Design and Analysis of Vaccine Trials for Emerging Infectious Disease Threats (7R01AI139761-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10247049. Licensed CC0.

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