Comparing statistical methods for detecting and estimating waning efficacy of rotavirus vaccines in developing countries

Haber, Michael; Tate, Jacqueline E.; Lopman, Benjamin A.; Qi, Wenrui; Ainslie, Kylie E. C.; Parashar, Umesh D.

doi:10.1080/21645515.2021.1968738

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…To determine the direction and magnitude of bias, we simulate an epidemic in a population under various frailty and vaccine protection distributions in the absence and presence of waning and evaluate the interplay between these factors. Commonly, hazard ratios are estimated with the Cox proportional hazards model and there are several standard extensions utilized in real-world studies [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. While Cox proportional hazard models were not intended to be time-varying, several approaches exist in order to make it applicable for measuring waning vaccine effectiveness.…”

Section: Introductionmentioning

confidence: 99%

Competing Heterogeneities in Vaccine Effectiveness Estimation

2023

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Understanding the waning of vaccine-induced protection is important for both immunology and public health. Population heterogeneities in underlying (pre-vaccination) susceptibility and vaccine response can cause measured vaccine effectiveness (mVE) to change over time, even in the absence of pathogen evolution and any actual waning of immune responses. We use multi-scale agent-based models parameterized using epidemiological and immunological data, to investigate the effect of these heterogeneities on mVE as measured by the hazard ratio. Based on our previous work, we consider the waning of antibodies according to a power law and link it to protection in two ways: (1) motivated by correlates of risk data and (2) using a within-host model of stochastic viral extinction. The effect of the heterogeneities is given by concise and understandable formulas, one of which is essentially a generalization of Fisher’s fundamental theorem of natural selection to include higher derivatives. Heterogeneity in underlying susceptibility accelerates apparent waning, whereas heterogeneity in vaccine response slows down apparent waning. Our models suggest that heterogeneity in underlying susceptibility is likely to dominate. However, heterogeneity in vaccine response offsets <10% to >100% (median of 29%) of this effect in our simulations. Our study suggests heterogeneity is more likely to ‘bias’ mVE downwards towards the faster waning of immunity but a subtle bias in the opposite direction is also plausible.

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Section: Introductionmentioning

confidence: 99%

Competing Heterogeneities in Vaccine Effectiveness Estimation

2023

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Estimating Waning of Vaccine Effectiveness: A Simulation Study

Nikas

Ahmed

Zarnitsyna

2022

Clinical Infectious Diseases

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Background 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 of vaccine-induced protection needs to be rigorously investigated. Methods To compare statistical methods for vaccine effectiveness (VE) estimation, we generated simulated data using a multiscale agent-based model of an epidemic with an acute viral infection and differing extents of VE waning. We apply a previously proposed framework for VE measures based on the observational data richness to assess changes of vaccine-induced protection over time. Results While VE measures based on hard-to-collect information (e.g. the exact timing of exposures) were accurate, usually VE studies rely on time-to-infection data and the Cox proportional hazard model. We found that its extension utilizing scaled Schoenfeld residuals, previously proposed for capturing VE waning, was unreliable in capturing both the degree of waning and its functional form and identified the mathematical factors contributing to this unreliability. We showed that partitioning time and including a time-vaccine interaction term in the Cox model significantly improved estimation of VE waning, even in the case of dramatic, rapid waning. We also proposed how to optimize the partitioning scheme. Conclusions While appropriate for rejecting the null hypothesis of no waning, scaled Schoenfeld residuals are unreliable for estimating the degree of waning. We propose a Cox-model-based method with a time-vaccine interaction term and further optimization of partitioning time. These findings may guide future analysis of VE waning data.

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Comparing statistical methods for detecting and estimating waning efficacy of rotavirus vaccines in developing countries

Cited by 2 publications

References 8 publications

Competing Heterogeneities in Vaccine Effectiveness Estimation

Competing Heterogeneities in Vaccine Effectiveness Estimation

Estimating Waning of Vaccine Effectiveness: A Simulation Study

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