Target Trial Emulation for Vaccines – Center for Health Decision Science

Target trial emulation is a causal inference framework that can be used to model and estimate clinical trial outcomes, expanding information available for decision-making when budgets, ethics, feasibility, or timing constrain the scope of traditional clinical trials. At a recent CHDS seminar, Kayoko Shioda presented current and forthcoming research on using TTE techniques to identify optimal vaccine dosing schedules. Shioda is Assistant Professor of Global Health at Boston University, and an infectious disease epidemiologist and veterinarian.

Shioda examined the optimal timing for administration of the second primary dose of the mRNA COVID-19 vaccine. Many US residents received their second dose outside the initially recommended range. The resulting data provide an opportunity to understand the impact of different schedules on both disease protection and adverse events from immunization.

However, using this type of observational data presents two key challenges. One is selection bias, in which a specific subset of the population with unique, confounding characteristics self-selects into a particular dosing schedule. A second is immortal time bias, which results because each cohort must remain infection-free before receiving a second dose, creating a guaranteed infection-free period for the cohort with longer intervals between doses.

The target trial emulation process mimics a clinical trial using observational data. It clones each person’s records and uses the inverse probability of censoring weights to address selection bias. This cloning allows the researchers to address immortal time bias. Dr. Shioda shared how these methods are supporting recommended dosing schedules for mRNA COVID-19 vaccines, as well as for Rotavirus and Pneumococcal conjugate vaccine.

Learn more: Read the article, Exploring the Application of Target Trial Emulation in Vaccine Evaluation: Scoping Review
Learn more: Read the article, Comparative Effectiveness of Alternative Intervals between First and Second Doses of the mRNA COVID-19 Vaccines