Biology subjects

Bellan, S.

Publications and source records attributed to Bellan, S..

3 recordsLinked to original sources

bioRxiv2018

Modeling Vaccine Trials in Epidemics with Mild and Asymptomatic Infection

Vaccine efficacy against susceptibility to infection (VES), regardless of symptoms, is an important endpoint of vaccine trials for pathogens with a high proportion of asymptomatic infection, as such infections may contribute to onward transmission and outcomes such as Congenital Zika Syndrome. However, estimating VES is resource-intensive. We aim to identify methods to accurately estimate VEs when limited information is available and resources are constrained. We model an individually randomized vaccine trial by generating a network of individuals and simulating an epidemic. The disease natural history follows a Susceptible, Exposed, Infectious and Symptomatic or Infectious and Asymptomatic, Recovered model. We then use seven approaches to estimate VES, and we also estimate vaccine efficacy against progression to symptoms (VEP). A corrected relative risk and an interval censored Cox model accurately estimate VES and only require serologic testing of participants once, while a Cox model using only symptomatic infections returns biased estimates. Only acquiring serological endpoints in a 10% sample and imputing the remaining infection statuses yields unbiased VES estimates across values of R0 and accurate estimates of VEP for higher values. Identifying resource-preserving methods for accurately estimating VES is important in designing trials for diseases with a high proportion of asymptomatic infection.

epidemiology↗

bioRxiv2017

Simulations for Designing and Interpreting Intervention Trials in Infectious Diseases

Here we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly in emerging infectious disease, that more accurately reflects the dynamics of the transmission process. Interventions in infectious diseases can have indirect effects on those not receiving the intervention as well as direct effects on those receiving the intervention. Combinations of interventions can have complex interactions at the population level. These often cannot be adequately addressed with standard study designs and analytic methods. Simulations can help to accurately represent transmission dynamics in an increasingly complex world which is critical for proper trial design and interpretation. Some ethical aspects of a trial can also be quantified using simulations. After a trial has been conducted, simulations can be used to explore possible explanations for the observed effects. A great deal is to be gained through a multidisciplinary approach that builds collaborations among experts in infectious disease dynamics, epidemiology, statistical science, economics, simulation methods and the conduct of clinical trials.

epidemiology↗

bioRxiv2017

Competing effects of indirect protection and clustering on the power of cluster-randomized controlled vaccine trials

Power considerations for trials evaluating vaccines against infectious diseases are complicated by indirect protective effects of vaccination. While cluster-randomized trials (cRCTs) are less statistically efficient than individually randomized trials (iRCT), a cRCTs ability to measure direct and indirect vaccine effects may mitigate the loss of efficiency due to clustering. Within cRCTs, the number and size of clusters affects three determinants of power: the effect size being measured, disease incidence, and intra-cluster correlation. We simulate trials conducted in a collection of small communities to assess how indirect protection and clustering affect the power of cRCTs and iRCTs during an emerging epidemic. Across diverse parameters, we find that within the same trial population, cRCTs are never more powerful than iRCTs, although the difference can be small. We also identify two effects that attenuate the loss of cRCT power traditionally associated with increased cluster size. First, if enrollment of fewer, larger clusters is performed to achieve higher vaccine coverage within vaccinated communities, this increases the effect to be measured and, consequently, power. Second, the greater rate of imported transmission in larger communities may increase the attack rate and similarly mitigate loss of power relative to a trial in many, smaller communities.

epidemiology↗