Exploring the Application of Target Trial Emulation in Vaccine Evaluation: Scoping Review and Recommendations for Future Studies

Abstract

Background: Target trial emulation has gained popularity in evaluating treatments and health interventions. Its application to infectious disease outcomes requires careful consideration, as infectious disease transmission violates the assumption of no interference. We conducted a scoping review to understand how target trial emulation approaches have been applied to vaccine evaluation. Methods: We conducted a systematic search of literature published in PubMed, Embase, and Web of Science until May 2024, using keywords related to target trial emulation, infectious diseases, and vaccines. Three independent reviewers screened titles and abstracts for relevance. Full-text articles meeting inclusion criteria were further assessed for eligibility. Results: Our search identified 236 studies. Of these, 30 original research studies employed target trial emulation approaches to evaluate vaccines, predominantly published from 2022 to 2024. Most studies (n=28, 93%) were conducted in high-income countries. The majority (n=27, 90%) evaluated the effect of COVID-19 vaccines, with one study each evaluating influenza, MPOX, and rotavirus vaccines. Nationwide healthcare databases were used in 17 studies (57%). Twenty-one studies (70%) conducted analysis among adults aged ≥18 years, while four studies (13%) focused on children <18 years. Most studies did not define the type of vaccine effect they evaluated (e.g., direct, indirect, total, or overall effect), and none incorporated interference in vaccine evaluation. Discussion: Our review highlights the increasing popularity of target trial emulation in vaccine evaluation following the COVID-19 pandemic. Further discussions are needed to understand how interference can be addressed within this framework.