Abstract: The COVID-19 pandemic has triggered explosive activities in searching for cures, including vac- cines against the SARS-CoV-2 infection. As of April 30, 2020, there are at least 102 COVID-19 vaccine development programs worldwide, the majority of which are in preclinical development phases, five are in phase I trial, and three are in phase I/II trial. Experts caution against rushing COVID-19 vaccine development, not only because the knowledge about SARS-CoV-2 is lack- ing (albeit rapidly accumulating), but also because vaccine development is a complex, lengthy process with its own rules and timelines. Clinical trials are critically important in vaccine devel- opment, usually starting from small-scale phase I trials and gradually moving to the next phases (II and III) after the primary objectives are met. This paper is intended to provide an overview on design considerations for vaccine clinical trials, with a special focus on COVID-19 vaccine de- velopment. Given the current pandemic paradigm and unique features of vaccine development, our recommendations from statistical design perspective for COVID-19 vaccine trials include: (1) novel trial design (e.g., master protocol) to expedite the simultaneous evaluation of multiple candidate vaccines or vaccine doses, (2) human challenge studies to accelerate clinical develop- ment, (3) adaptive design strategies (e.g., group sequential designs) for early termination due to futility, efficacy, and/or safety, (4) extensive modeling and simulation to characterize and estab- lish long-term efficacy based on early-phase or short-term follow-up data, (5) safety evaluation as one of the primary focuses throughout all phases of clinical trials, (6) leveraging real-world data and evidence in vaccine trial design and analysis to establish vaccine effectiveness, and (7) global collaboration to form a joint development effort for more efficient use of resource and expertise and data sharing.

Key words: adaptive design, human challenge trials, master protocol, sample size, SARS-CoV-2, vaccine efficacy