Recommendations for estimating and reporting vaccine effectiveness by time since vaccination: a COVID-19 case study - Report - MDSpire

Recommendations for estimating and reporting vaccine effectiveness by time since vaccination: a COVID-19 case study

  • By

  • Esther Kissling

  • Baltazar Nunes

  • Mariëtte Hooiveld

  • Iván Martínez-Baz

  • Susana Monge

  • Chris Robertson

  • Mirjam Knol

  • Noémie Sève

  • Ivan Mlinarić

  • Lisa Domegan

  • Ausenda Machado

  • Heather Whitaker

  • Mihaela Lazar

  • Adam Meijer

  • Theresa Enkirch

  • Itziar Casado

  • Gloria Pérez-Gimeno

  • Naoma William

  • Vincent Enouf

  • Sanja Kurečić Filipović

  • Adele McKenna

  • Ana Paula Rodrigues

  • Simon de Lusignan

  • Olivia-Carmen Timnea

  • Neus Latorre-Margalef

  • Jesús Castilla

  • Francisco Pozo

  • Mark Hamilton

  • Shirley Masse

  • Maja Ilić

  • Luca Basile

  • Joan O’Donnell

  • Raquel Guiomar

  • Maximilian Riess

  • Rodica-Manuela Popescu

  • Angela M C Rose

  • Nick Andrews

  • Sabrina Bacci

  • Lucia Pastore Celentano

  • Marta Valenciano

  • Alain Moren

  • Philippe Beutels

  • Niel Hens

  • on behalf of I-MOVE-COVID-19 and ECDC primary care study teams

  • November 17, 2025

  • 0 min

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Guidelines for Assessing COVID-19 Vaccine Effectiveness by Time Since Vaccination

Overview

This report provides practical recommendations for estimating and presenting COVID-19 vaccine effectiveness (VE) over time since vaccination (TSV) using case–control studies. It emphasizes the importance of accounting for TSV to accurately interpret VE changes, compare across variants, age groups, and vaccine brands, and avoid confounding by timing of vaccination or variant circulation.

Background

Randomized controlled trials provide initial vaccine efficacy estimates under controlled conditions, but observational studies are essential to assess real-world VE and its waning over time. Case–control and cohort studies have been widely used to estimate VE by TSV for various vaccines, including COVID-19. Accurate VE estimates by TSV are critical for understanding protection dynamics, especially given the frequent emergence of SARS-CoV-2 variants with differing immune escape properties. Without accounting for TSV, VE comparisons across variants or vaccine brands may be misleading due to differences in timing of vaccination or variant predominance.

Data Highlights

The article discusses methodological considerations rather than presenting specific numerical VE data. It highlights that VE is estimated as (1 - odds ratio) × 100 using logistic regression in case–control studies. TSV is calculated as the difference between vaccination date and index date (e.g., symptom onset). The report includes recommendations for descriptive analyses such as plotting vaccinated cases and controls by TSV to guide modeling choices.

Key Findings

  • Estimating VE by TSV is essential to understand waning immunity and to enable meaningful comparisons across variants, age groups, and vaccine brands.
  • Case–control studies should define study population, index dates, vaccination exposure, and outcomes carefully to ensure valid VE estimates by TSV.
  • TSV is calculated as the interval between vaccination date and index date; accurate and complete vaccination and index date data are critical.
  • Two main modeling approaches exist: categorical TSV modeling and continuous TSV modeling, with choice depending on study objectives.
  • Descriptive analyses such as plotting vaccinated cases and controls by TSV help interpret VE trends and guide modeling.
  • Accounting for variant circulation periods or restricting analyses to specific variants is important to distinguish waning immunity from immune escape effects.

Clinical Implications

Clinicians and researchers should interpret COVID-19 VE estimates in the context of time since vaccination to understand the duration of protection and inform booster timing. Vaccine brand comparisons require adjustment for TSV to avoid confounding by vaccination timing or variant prevalence. Accurate VE by TSV estimates support public health decisions on vaccination strategies during evolving variant landscapes.

Conclusion

This guidance enhances the quality and comparability of COVID-19 VE estimates by TSV in case–control studies, facilitating better understanding of vaccine protection dynamics. Ongoing refinement and application of these recommendations will improve epidemiological assessments and inform vaccination policy.

References

  1. WHO/ECDC/CDC -- COVID-19 Vaccine Effectiveness Studies Guidance
  2. UK Health Security Agency -- COVID-19 Vaccine Surveillance Reports

Original Source(s)

Recommendations for estimating and reporting vaccine effectiveness by time since vaccination: a COVID-19 case study

  • by Esther Kissling, Baltazar Nunes, Mariëtte Hooiveld, Iván Martínez-Baz, Susana Monge, Chris Robertson, Mirjam Knol, Noémie Sève, Ivan Mlinarić, Lisa Domegan, Ausenda Machado, Heather Whitaker, Mihaela Lazar, Adam Meijer, Theresa Enkirch, Itziar Casado, Gloria Pérez-Gimeno, Naoma William, Vincent Enouf, Sanja Kurečić Filipović, Adele McKenna, Ana Paula Rodrigues, Simon de Lusignan, Olivia-Carmen Timnea, Neus Latorre-Margalef, Jesús Castilla, Francisco Pozo, Mark Hamilton, Shirley Masse, Maja Ilić, Luca Basile, Joan O’Donnell, Raquel Guiomar, Maximilian Riess, Rodica-Manuela Popescu, Angela M C Rose, Nick Andrews, Sabrina Bacci, Lucia Pastore Celentano, Marta Valenciano, Alain Moren, Philippe Beutels, Niel Hens, on behalf of I-MOVE-COVID-19 and ECDC primary care study teams

  • November 17, 2025

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