(277) RSV Outcomes Study Extension (ROSE): Epidemiological and Operational Considerations for an Observational Study Linking Real-World Data through Tokenization to the mRNA-1345 RSV Vaccine Phase 3 Clinical Trial Data in Adults

Publication Number: 1267

Background: The 21st Century Cures Act encourages the use of real-world evidence studies to support and accelerate regulatory decision making on medical products in the United States. However, to-date, regulatory guidance is not final, and proof-of-concept studies are limited. Here, we describe the epidemiologic and operational challenges encountered during the design of a real-world, longitudinal cohort study based in the US, Respiratory Syncytial Virus (RSV) Outcomes Study Extension (ROSE; NCT05572658). This study links through tokenization to the ongoing global mRNA-1345 RSV vaccine randomized phase 3 pivotal efficacy clinical trial in adults (ConquerRSV; NCT05127434).

Objectives: To describe the rationale, study design, and operational implementation of ROSE.

Methods: A cross-functional team explored a range of scientific and operational questions to inform and implement the goals, design, and operations of the study.

Results: The strategic goals identified for ROSE were to 1) examine additional health and economic outcomes not included in the ConquerRSV trial; 2) extend the length of participant follow-up from the trial using real-world data; and 3) generate real-world evidence on the mRNA-1345 RSV vaccine earlier than traditional study designs that are not linked to Phase 3 clinical trial data. To increase study power, the reference group will consist of a matched external control arm combined with placebo participants from ConquerRSV who consented to participate in ROSE. A feasibility survey was given to 135 US sites and returned by 116 sites, revealing that interest in participation was high (>85%). As of February 9, 2023, 7577 participants have consented to participate in ROSE (108% of the original 7,000 target and 75.8% of the new 10,000 target). Assessment of US data sources and tokenization methodologies that are fit-for-purpose are ongoing.

Conclusions: Observational studies linking clinical trial data to real-world data demand a variety of expertise and are best pursued in cross-functional partnerships. While some tasks must occur sequentially, many activities can be pursued in parallel. As best practices are still emerging for this novel approach, sharing information across the research community is important for the establishment of methodological rigor and to demonstrate the value of real-world evidence studies that link and/or enhance information generated through randomized clinical trials.