Insight and benefits from vaccine clinical trials with adaptive designs: a scoping review

Vaccines are vital to global public health, especially as population growth and climate change increase the risk of infectious disease outbreaks. While randomized controlled trials (RCTs) remain the gold standard for evaluating vaccine safety and efficacy, traditional RCTs often face limitations including time constraints, resource demands, and ethical concerns. Adaptive endpoint-driven trial designs offer a promising alternative by allowing protocol modifications based on interim analyses while preserving scientific validity. Despite their potential, the adoption of such designs in prophylactic vaccine trials remains limited, with few real-world examples. This scoping review investigates the implementation of adaptive endpoint-driven methodologies in prophylactic vaccine RCTs. Using PRISMA-P and Joanna Briggs Institute guidelines, a systematic search was conducted across MEDLINE, Embase, and ClinicalTrials.gov. Eligible studies were Phase I-III vaccine RCTs employing adaptive endpoint-driven strategies. Multiple reviewers independently extracted data and assessed risk of bias, with findings synthesized descriptively. Seven studies met inclusion criteria, demonstrating adaptive methods such as interim analyses, sample size re-estimation, and modification of trial arms. Endpoints were identified through clinical evaluations, laboratory confirmation, and epidemiological surveillance, often supported by digital tools like mobile-based reporting and real-time diagnostics. These approaches enhanced flexibility and operational efficiency but faced challenges including statistical complexity, regulatory constraints, and maintaining control of bias. The findings highlight the emerging utility of adaptive endpoint-driven designs in vaccine research. Future efforts should focus on improving endpoint tools, addressing regulatory concerns, and evaluating how adaptive designs impact approval timelines and public health outcomes.