Background and rationale {6a}
CF, Pulmonary exacerbations, PEx, lung damage, CF PEx
CYSTIC FIBROSIS, DISEASE, CYSTIC FIBROSIS, RARE DISEASES
Cystic fibrosis (CF) is an inherited, life-limiting disease affecting multiple organs, predominantly the lungs. Pulmonary exacerbations (PEx) are a hallmark of disease and are thought to drive progressive lung damage; it is estimated that a quarter of people fail to fully recover lung function after these episodes [Randomized controlled trials are rightfully considered the gold standard for generating evidence to inform clinical practice and policy [Newer approaches to clinical research offer an opportunity to generate high-quality evidence for guiding patient management, including in complex and rare diseases. These innovations, including nesting of studies within registries or large cohorts, pragmatism and healthcare embedding, and outcome or response-adaptation, focus on informing real world decision-making, may be more conducive to high levels of participation, and may offer greater flexibility and statistical efficiency than traditional clinical trials [Here, we present a core protocol for studying the management of PEx in the BEAT CF (Bayesian Evidence Adaptive Treatment for people with Cystic Fibrosis) platform. The PEx core protocol sets out the establishment of a prospective, multi-site cohort designed to perpetually enroll and follow-up people with CF and systematically capture data on the management and outcomes of any PEx requiring intensive therapy (PERIT). Here, a PERIT is pragmatically defined as an acute or subacute deterioration in lung function or symptoms resulting in (possibly multimodal) therapy comprising initiation of at least one intravenous antibiotic. It is anticipated that most cohort participants will become eligible to participate in cohort-nested sub-studies, including a PEx Treatment Platform in which selected aspects of PERIT management will be randomly assigned.The protocol documentation for BEAT CF is modular and hierarchical (Fig. BEAT CF protocol documentation for the BEAT CF PEx cohort and related and nested sub-studies