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

Background: Target trial emulation (TTE) 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 TTE 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 TTE, 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 keyword-based search and citation search identified a total of 240 studies. Of these, 34 original research studies used TTE approaches to evaluate vaccines, predominantly published from 2022 to 2024. Most studies (n=32, 94%) were conducted in high-income countries. The majority (n=31, 91%) 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 (50%). Twenty-one studies (62%) conducted analysis among adults aged ≥18 years, while six studies (18%) focused on children <18 years. Most studies did not define which of the four effects of vaccination they evaluated (direct, indirect, total, or overall effect), and none incorporated interference in vaccine evaluation. Conclusions: Our review highlights the increasing popularity of TTE in vaccine evaluation following the COVID-19 pandemic. Further discussions are needed to establish TTE approaches to estimating four effects of vaccination, using large, routinely collected data.