Core Elements for Advanced Stage Clinical Trials of COVID-19 Vaccine Candidates: Aspects to Consider

This Summary Document sets out core elements to be considered when designing advanced stage clinical trials of COVID-19 vaccine candidates. Advanced stage clinical trials (Phase 2b to 3) are typically conducted to evaluate the efficacy (or immunogenicity, where applicable) including in special populations (e.g. paediatric, geriatric, co-morbidities), and expand the safety database. This development pathway should allow rapid regulatory licensure (or other equivalent). Additional trials for special objectives (e.g. lot to lot consistency) may be considered separately from this pathway.
The sponsor is responsible for the clinical development of the COVID-19 vaccine candidate and will include construct- and platform-specific elements in the trial design, within the regulatory framework. However, some elements should be considered specifically in the light of need for accelerated development in the pandemic situation. An event driven trial with periodic interim endpoints and dynamic sample size may, for example, allow early determination of vaccine efficacy (VE) through pre-defined interim analysis (IA).
The control measures in community in light of COVID outbreaks may disturb trial continuity at one or multiple sites and there should be contingency plans to deal with the same. Vaccine-mediated enhanced disease (VMED) should be monitored but put in the context of data coming from early stage trials as well as animal studies. Standardization of diagnostic criteria, efficacy endpoints, follow up duration, immunogenicity testing will allow comparisons across programs.