Regulatory workshop on standardisation of clinical procedures, endpoints and data robustness of human challenge studies – A stakeholder meeting report

Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs. Key discussions focused on refining trial protocols to balance statistical power with participant burden, overseen by a data safety monitoring board. The meeting emphasised the importance of harmonizing CHIM protocols to ensure robust, reproducible, and transparent research. Mandatory trial registration and adherence to the Findable, Accessible, Interoperable, and Reusable (FAIR) data principles were recommended to enhance data reuse and scientific value. This report consolidates efforts to standardise CHIM protocols, essential for accelerating therapeutic innovations and advancing global health research. • Symptomatic human challenge models are more useful for drug development than models showing infection only. • Adaptive dose-escalation designs shorten timelines and require fewer subjects to progress to the next dose. • High standards and harmonisation in ethics, subject engagement, study conduct, and reporting are essential in CHIM trials. • Participant data, including adverse events, should be uniformly reported in machine-readable formats to enable data reuse. • Conducting RSV CHIMs in outpatient settings reduces time, participant burden, and drug development costs.