PAtient-Centric epilepsy clinical trIal model For Improved health outcomes using Cannabidiol (PACIFIC study)-a...

Clinical trials for rare epilepsies face substantial methodological and ethical challenges. Small and heterogeneous populations, coupled with limited validated outcome measures, often render traditional designs underpowered and unable to capture outcomes that are meaningful to patients and their families. Innovative approaches-such as decentralised, adaptive, and participatory designs-offer potential solutions but have rarely been systematically applied in this context.

We employed an exploratory three-phase sequential mixed-methods design to co-design a patient-centred clinical trial protocol for rare epilepsies in Australia. An expression-of-interest process recruited 40 participants, equally distributed across four advisory groups: patients, clinicians, researchers, and industry representatives. Phase 1 surveys collected demographic information, trial preferences, digital literacy, and perspectives on participation. Phase 2 comprised semi-structured interviews, analysed using reflexive thematic analysis, to identify themes relevant to trial design. In Phase 3, a consensus-driven process involving four structured online workshops with a multidisciplinary subcommittee translated these findings into a trial protocol recommendation.

Four priorities emerged: (1) decentralised trial models to improve access and inclusion, particularly through home-based care; (2) embedding cultural safety and systems integration to support diversity; (3) prioritising outcomes beyond seizure reduction, including quality of life and patient-reported measures; and (4) improving communication and accessibility through digital innovation. These insights informed recommendations for an ethics-approved protocol emphasising inclusivity, feasibility, and real-world relevance.

This study demonstrates the feasibility of participatory co-design in developing rare epilepsy trial protocols. Embedding patient perspectives and adopting innovative methodologies can enhance scientific rigour, build trust, and strengthen the clinical and policy impact of rare disease research.