Related papers: Assessing surrogate endpoints in vaccine trials wi…
A surrogate endpoint S in a clinical trial is an outcome that may be measured earlier or more easily than the true outcome of interest T. In this work, we extend causal inference approaches to validate such a surrogate using potential…
Developing accurate and reliable methods to estimate vaccine protection is a key goal in immunology and public health. While several statistical methods have been proposed, their potential inaccuracy in capturing fast intra-seasonal waning…
When direct measurement of a clinically relevant primary endpoint in a clinical trial is infeasible, a surrogate endpoint may be used instead to infer treatment effects. Trial-level surrogates predict the average treatment effect on the…
In vaccine trials with long-term participant follow-up, it is of great importance to identify surrogate markers that accurately infer long-term immune responses. These markers offer practical advantages such as providing early, indirect…
The primary endpoint in oncology is usually overall survival, where differences between therapies may only be observable after many years. To avoid withholding of a promising therapy, preliminary approval based on a surrogate endpoint is…
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…
The advent and subsequent widespread availability of preventive vaccines has altered the course of public health over the past century. Despite this success, effective vaccines to prevent many high-burden diseases, including HIV, have been…
Adaptive subgroup enrichment design is an efficient design framework that allows accelerated development for investigational treatments while also having flexibility in population selection within the course of the trial. The adaptive…
We introduce in this paper an extension of the meta-analytic (MA) framework for evaluating surrogate endpoints. While the MA framework is regarded as the gold standard for surrogate endpoint evaluation, it is limited in its ability to…
Prevalent cohort sampling is commonly used to study the natural history of a disease when the disease is rare or it usually takes a long time to observe the failure event. It is known, however, that the collected sample in this situation is…
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…
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…
An intermediate response measure that accurately predicts efficacy in a new setting can reduce trial cost and time to product licensure. In this paper, we define a trial level general surrogate as a trial level intermediate response that…
Mediation analysis is a useful tool to evaluate surrogate endpoints in clinical trials. We propose a novel method, the M-survival learner, for estimating heterogeneous indirect treatment effects in the presence of censored outcomes. The…
Surrogate markers are often used in clinical trials to evaluate treatment effects when primary outcomes are costly, invasive, or take a long time to observe. However, reliance on surrogates can lead to the surrogate paradox, where a…
A common practice in clinical trials is to evaluate a treatment effect on an intermediate endpoint when the true outcome of interest would be difficult or costly to measure. We consider how to validate intermediate endpoints in a…
Estimating the long-term effects of treatments is of interest in many fields. A common challenge in estimating such treatment effects is that long-term outcomes are unobserved in the time frame needed to make policy decisions. One approach…
Measurement error in the covariate of main interest (e.g. the exposure variable, or the risk factor) is common in epidemiologic and health studies. It can effect the relative risk estimator or other types of coefficients derived from the…
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…
Given the long follow-up periods that are often required for treatment or intervention studies, the potential to use surrogate markers to decrease the required follow-up time is a very attractive goal. However, previous studies have shown…