Exploring the Application of Target Trial Emulation in Vaccine Evaluation: Scoping Review

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. Thus, we conducted a scoping review to understand how TTE approaches have been applied to vaccine evaluation. We searched literature published in PubMed, Embase, and Web of Science until May 2024, using keywords related to TTE, infectious diseases, and vaccines. Full-text articles meeting inclusion criteria were further assessed for eligibility. Our keyword-based search and citation search identified a total of 241 studies. Of these, 35 original research studies used TTE approaches to evaluate vaccines, predominantly published from 2022 to 2024. The majority (n=32, 91%) evaluated the effect of COVID-19 vaccines, with one study each evaluating influenza, mpox, and rotavirus vaccines. 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. 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.