WHO Workshop Report: Regulatory Science to Inform Clinical Pathways for Shigella Vaccines Intended for Use in Children in Low- and Middle-Income Countries

Infectious diarrhea caused by <i>Shigella</i> remains a significant global health concern, and several vaccine candidates are approaching phase III clinical studies in the target population of young children in low- and middle-income countries. The World Health Organization (WHO) has published preferred product characteristics (PPCs) for <i>Shigella</i> vaccines to provide strategic guidance that aids in advancing product development and highlights policy considerations for use in LMIC settings where the vaccine is most needed. However, the selection of appropriate clinical endpoints was not clearly defined within the PPCs and remains an important issue for phase III study design. Previously, an expert panel identified areas of alignment and consensus on many clinical study design components while also recognizing that further discussions and data were required to solidify recommendations on key study design aspects. Therefore, WHO convened a diverse range of stakeholders, including manufacturers, regulators, and policymakers across national, regional, and global levels, with the aim of achieving consensus and soliciting inputs from the regulatory community surrounding vaccine phase III study design considerations. The intent of this report is to outline the key points from those discussions to inform the phase III design strategies and investment decisions of product developers and donors and to share recommendations for next steps.