Key study information and aims for the CARE PREP trial. Key study information and aims What is CARE PREP? Cavernous malformations: A Randomised Efficacy PREcision medicine Platform trial (CARE PREP) was funded by an NIHR EME 'acceleration award' by NIHR in August 2022 to develop a grant application for an international precision medicine platform trial. The project started in September 2022 and will last for 12 months. Research questions What is the optimal design of an international platform trial of precision medicine with drugs for cerebral cavernous malformations (CCM, also known as brain cavernomas)? Is delivery of the optimal platform trial design feasible? Background Symptomatic CCM are a rare sporadic or familial disease. Approximately 160 people are first diagnosed with symptomatic CCM in the UK annually, but the impact of CCM is disproportionately high because they are usually diagnosed in young adults who are at risk of stroke due to intracranial haemorrhage (rate 0.8% to 6.2% per year) and epileptic seizures. In 2015, a James Lind Alliance Priority Setting Partnership ranked targeted drug therapies as the fourth of the top 10 research priorities for CCM. There are no disease-modifying drugs for CCM, but there are several promising candidates for sporadic or familial CCM with proof of concept in human and animal studies. At the time of applying, there are no platform trials for CCM. Aims and objectives Consolidate and initiate international collaborations between CCM researchers, CCM patient and public involvement (PPI) groups, CCM research networks, and commercial partners. Understand regulatory and governance requirements in collaborating countries. Finalise a protocol for an efficient, international platform trial of multiple drugs using precision medicine (sporadic vs. familial CCM) that is feasible and acceptable to patients and regulators. Estimate the research, support and treatment costs of the platform trial. Methods A trial manager will support the chief investigator to lead our multidisciplinary international collaboration in a series of virtual meetings, and one face-to-face meeting. A PPI Advisory Group will inform the coapplicants about patients’ preferences for study design, and recommend how to maximise equality, diversity, and inclusion. Edinburgh Innovations will establish collaborations with pharmaceutical companies that manufacture candidate drugs. The trial manager will assess feasibility by scoping regulatory requirements for platform trials in co-applicants’ countries, potential funding agencies, and clinical networks that might support recruitment. Co-applicants will refine hypotheses, eligibility and precision/stratification criteria, interventions, comparator(s), adaptive trial design, allocation ratio, clinical/intermediate outcomes (prioritised with PPI input), and anticipated treatment effects, informed by scenarios simulated by the statistician using variations in these parameters. The final protocol for the platform trial will inform a comprehensive estimate of the budget, for a stage 1 submission to NIHR EME. Timelines for delivery Months 1-12: Co-applicants meet monthly and consolidate collaborations. Two-monthly PPI Advisory Group meetings. Months 1-6: Identify regulatory requirements, funding opportunities, and CCM clinical networks; protocol design and development. Months 1-8: Develop commercial partnerships. Months 7-8: Protocol completion with a feasibility assessment and budget. Month 9: NIHR EME stage 1 submission. Months 10-12: NIHR EME stage 2 preparation. Anticipated impact and dissemination This award will catalyse the design, delivery, and assessment of the feasibility of a protocol and funding application for the first CCM platform trial of drugs. We will present at the 2022 CCM International Scientific Meeting, produce newsletters for collaborators and PPI groups, and release a final report. Who’s involved? Steering Committee: Rustam Al-Shahi Salman Christopher Weir Richard Parker Roberto Latini Issam Awad Helen Kim PPI Advisory Group: David White Jana Bergholtz Cornelia Lee Carlos Casaus João Própero Luís Project Manager: Kasia Adamczuk - Kasia.Adamczuk@ed.ac.uk Collaborators: pending This article was published on 2024-09-24
