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Assessing vaccine durability in randomized trials following placebo crossover
Jonathan Fintzi1, Dean Follmann1
1Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, 5601, Maryland, USA.
Statistics in Medicine
|April 30, 2021
Summary
Even with placebo crossover in vaccine trials, we can still accurately assess long-term vaccine efficacy (VE). Our methods recover the true VE profile, regardless of when participants switch to the vaccine.
Area of Science:
- Vaccinology
- Clinical Trials
- Epidemiology
Background:
- Randomized vaccine trials are crucial for determining vaccine efficacy (VE) and protection durability.
- Established vaccine efficacy in COVID-19 trials necessitates offering vaccines to placebo groups, leading to crossover.
Purpose of the Study:
- To develop methods for analyzing vaccine durability after placebo crossover.
- To demonstrate that vaccine efficacy profiles are recoverable even with placebo crossover.
Main Methods:
- Utilized proportional hazards regression models to estimate efficacy.
- Employed simulations to explore the impact of placebo crossover on VE estimation under various scenarios.
- Applied methods to simulated COVID-19 vaccine trials with 2-year follow-up.
Main Results:
- Vaccine efficacy profiles are recoverable in trials with placebo crossover, irrespective of crossover timing.
- The VE profile is recoverable without assumptions on the efficacy dynamics, provided it applies to newly vaccinated individuals.
- Simulations confirmed the robustness of the methods across different efficacy waning patterns and study designs.
Conclusions:
- Placebo crossover in vaccine trials does not preclude accurate assessment of long-term vaccine efficacy.
- Developed analytical methods enable robust estimation of vaccine efficacy and durability, even after placebo crossover.
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