Study Design
Exploring the Application of Target Trial Emulation in Vaccine Evaluation: Scoping Review Kayoko Shioda* Kayoko Shioda Kayoko Shioda Toshiaki Komura
Background: Target Trial Emulation has gained popularity in evaluating treatments and health interventions. However, its application to infectious disease outcomes requires careful consideration, as infectious diseases violate the assumption of no interference. We conducted a scoping review to understand how target trial emulation approaches have been applied for vaccine evaluation and how the indirect effects (or spillover effects) of the vaccines have been assessed in the target trial emulation framework.
Methods: We conducted a systematic search of literature published in PubMed and Embase between January 2012 and October 2023, using keywords related to target trial emulation, infectious diseases, and vaccines. Two independent reviewers screened titles and abstracts for relevance. Full-text articles meeting inclusion criteria were further assessed for eligibility.
Results: Our search identified 117 studies. Of these, 25 original research studies employed target trial emulation approaches to estimate the effect of vaccines, predominantly published in 2022 and 2023. Most studies evaluated the effect of COVID-19 vaccines, except for one that evaluated rotavirus vaccines. The majority used Kaplan-Meier estimator and/or Cox proportional hazards model, while two applied the cumulative incidence function and Fine-Gray model to adjust for competing risks. Most studies did not define the type of vaccine effect they evaluated (e.g., direct, indirect, total, or overall effect). None of the studies addressed interference or estimated the indirect effect of vaccines.
Discussion: Our review highlights the increasing popularity of target trial emulation in vaccine evaluation, but indirect effects have been overlooked. Agent-based modeling is a potential solution, as demonstrated in studies evaluating pre-exposure prophylaxis for HIV prevention.