Related papers: Distinguishing immunological and behavioral effect…
Cluster-randomized trials are often conducted to assess vaccine effects. Defining estimands of interest before conducting a trial is integral to the alignment between a study's objectives and the data to be collected and analyzed. This…
We review vaccine efficacy (VE) estimands for susceptibility in individual randomized trials with natural (unmeasured) exposure, where individual responses are measured as time from vaccination until an event (e.g., disease from the…
Pathogens usually exist in heterogeneous variants, like subtypes and strains. Quantifying treatment effects on the different variants is important for guiding prevention policies and treatment development. Here we ground analyses of…
Observational data are often used to estimate real-world effectiveness and durability of vaccines. A sequence of trials can be emulated to draw inference from such data while minimizing selection bias, immortal time bias, and confounding.…
Determining whether vaccine efficacy wanes is important for individual and public decision making. Yet, quantification of waning is a subtle task. The classical approaches cannot be interpreted as measures of declining efficacy unless we…
We review standard mediation assumptions as they apply to identifying antibody effects in a randomized vaccine trial and propose new study designs to allow identification of an estimand that was previously unidentifiable. For these…
Real-world vaccine effectiveness has increasingly been studied using matching-based approaches, particularly in observational cohort studies following the target trial emulation framework. Although matching is appealing in its simplicity,…
Knowledge of the protection afforded by vaccines might, in some circumstances, modify a vaccinated individual's behaviour, potentially increasing exposure to pathogens and hindering effectiveness. Although vaccine studies typically do not…
During the COVID-19 pandemic, estimating the total deaths averted by vaccination has been of great public health interest. Instead of estimating total deaths averted by vaccination among both vaccinated and unvaccinated individuals, some…
Safe and effective preventive vaccines have the potential to help stem the HIV epidemic. The efficacy of such vaccines is typically measured in randomized, double-blind phase IIb/III trials and described as a reduction in newly acquired HIV…
Knowing the true effect size of clinical interventions in randomised clinical trials is key to informing the public health policies. Vaccine efficacy is defined in terms of the relative risk or the ratio of two disease risks. However, only…
Vaccine randomized trials are typically designed to be blinded, ensuring that the estimated vaccine efficacy (VE) reflects the immunological effect of the vaccine. When blinding is broken, however, the estimated VE reflects not only the…
Estimands can help clarify the interpretation of treatment effects and ensure that estimators are aligned to the study's objectives. Cluster randomised trials require additional attributes to be defined within the estimand compared to…
The response of the immune system to different vaccination patterns is studied with a simple model. It is argued that the history and characteristics of the pattern defines very different secondary immune responses in the case of infection.…
Defining and identifying causal intervention effects for transmissible infectious disease outcomes is challenging because a treatment -- such as a vaccine -- given to one individual may affect the infection outcomes of others.…
Understanding vaccine effects on post-infection outcomes is critical for evaluating the full value proposition of a vaccine. However, defining appropriate causal effects on such outcomes is challenging because infection is affected by…
In order to meet regulatory approval, pharmaceutical companies often must demonstrate that new vaccines reduce the total risk of a post-infection outcome like transmission, symptomatic disease, severe illness, or death in randomized,…
Knowing whether vaccine protection wanes over time is important for health policy and drug development. However, quantifying waning effects is difficult. A simple contrast of vaccine efficacy at two different times compares different…
Suppose one has data from one or more completed vaccine efficacy trials and wishes to estimate the efficacy in a new setting. Often logistical or ethical considerations make running another efficacy trial impossible. Fortunately, if there…
In settings where units' outcomes are affected by others' treatments, there has been a proliferation of ways to quantify effects of treatments on outcomes, including via indirect exposure to other units' treatments. Here we consider two…