Affiliation:
1. Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, 5601 Fishers Lane, Bethesda, MD 20892, USA
Abstract
Summary
Vaccine trials are generally designed to assess efficacy on clinical disease. The vaccine effect on infection, while important both as a proxy for transmission and to describe a vaccine’s entire effects, requires frequent (e.g., twice a week) longitudinal sampling to capture all infections. Such sampling may not always be feasible. A logistically easy approach is to collect a sample to test for infection at a regularly scheduled visit. Such point or cross-sectional sampling does not permit estimation of classic vaccine efficacy on infection, as long duration infections are sampled with higher probability. Building on work by Rinta-Kokko and others (2009) and Lipsitch and Kahn (2021), we evaluate proxies of the vaccine effect on transmission at a point in time; the vaccine efficacy on prevalent infection and on prevalent viral load, VE$_{\rm PI}$ and VE$_{\rm PVL}$, respectively. Longer infections with higher viral loads should have more transmission potential and prevalent vaccine efficacy naturally captures this aspect. We demonstrate how these parameters obtain from an underlying proportional hazards model for infection and allow for waning efficacy on infection, duration, and viral load. We estimate these parameters based on regression models with either repeated cross-sectional sampling or frequent longitudinal sampling. We evaluate the methods by simulation and analyze a phase III vaccine trial with polymerase chain reaction (PCR) cross-sectional sampling for subclinical infection.
Publisher
Oxford University Press (OUP)
Subject
Statistics, Probability and Uncertainty,General Medicine,Statistics and Probability
Reference18 articles.
1. The prevalent cohort study and the acquired immunodeficiency syndrome;Brookmeyer,;American Journal of Epidemiology,1987
2. Some statistical models for limited dependent variables with application to the demand for durable goods;Cragg,;Econometrica: Journal of the Econometric Society,1971
3. Modeling the progression of HIV infection;Degruttola,;Journal of the American Statistical Association,1991
4. A deferred-vaccination design to assess durability of COVID-19 vaccine effect after the placebo group is vaccinated;Follmann,;Annals of Internal Medicine,2021
5. Incorporating founder virus information in vaccine field trials;Follmann,;Biometrics,2015
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献