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The COVID-19 pandemic due to the novel coronavirus SARS CoV-2 has inspired remarkable breakthroughs in development of vaccines against the virus and the launch of several phase 3 vaccine trials in Summer 2020 to evaluate vaccine efficacy…
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.…
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…
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…
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…
Clinical trials of a vaccine during an epidemic face particular challenges, such as the pressure to identify an effective vaccine quickly to control the epidemic, and the effect that time-space-varying infection incidence has on the power…
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,…
The interpretation of vaccine efficacy estimands is subtle, even in randomized trials designed to quantify immunological effects of vaccination. In this article, we introduce terminology to distinguish between different vaccine efficacy…
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…
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,…
I present here longitudinal evaluation of T and B cell immunity to SARS-CoV2 and variants of concern (VOC) from a single subject (me) over an entire year post vaccination. After enrolling in the Moderna phase III clinical trial, I collected…
It is often of interest to study the association between covariates and the cumulative incidence of a right-censored time-to-event outcome. When time-varying covariates are measured on a fixed discrete time scale, it is desirable to account…
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…
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…
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 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…
Refined vaccine regimens containing variant-matched inserts are often authorized based on historical phase 3 efficacy trials together with immunobridging studies. Phase 3 trials are essential for establishing immune biomarkers that reliably…
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…
Motivated by a clinical trial conducted by Janssen Pharmaceuticals in which a flexible dosing regimen is compared to placebo, we evaluate how switchers in the treatment arm (i.e., patients who were switched to the higher dose) would have…
Background: The Cox model and its extensions assuming proportional hazards is widely used to estimate vaccine efficacy (VE). In the typical situation that VE wanes over time, the VE estimates are not only sensitive to study duration and…