Using Real-World Research to Study the Impact of Chronic Daily Therapy Discontinuation in Cystic Fibrosis: The Home-Reported Outcomes in Cystic Fibrosis 2 Study Design.

Background: Chronic daily therapies (CDTs) are the foundation of clinical care for people with cystic fibrosis (CF), but these therapies impose considerable burden. In the era of elexacaftor/tezacaftor/ivacaftor (ETI) therapy, it is not clear if CDT discontinuation would lead to a greater decrease in lung function. Research Question: In people with CF who are taking or about to start ETI, does CDT discontinuation lead to lower lung function at 12 months? Study Design and Methods: People with CF who are aged 12 years or older and receiving or about to start ETI therapy were included in the Home-Reported Outcomes in Cystic Fibrosis 2 (HERO-2) study, an observational cohort study that used real-world research principles. Recruitment for HERO-2 used a multimodal approach consisting of recruitment sites, referral sites, and community-based strategies. The sole method of study engagement for participants was through the Folia Health application, which participants used to track CDT and symptoms, while completing monthly validated patient-reported assessments. Demographic and clinical data, including spirometry findings, were collected through linkage with the Cystic Fibrosis Foundation Patient Registry (CFFPR). The study was designed to detect a difference of 3% in FEV Results: The multimodal approach to recruitment and broad inclusion criteria allowed HERO-2 to recruit rapidly from > 70 sites, including smaller affiliate centers and community-based outreach sites. The protocol is still being executed, with anticipated results to be published when the complete CFFPR data are available. Interpretation: To our knowledge, HERO-2 is the first study in the population with CF that was designed using real-world research principles. Trial Registry: ClinicalTrials.gov; No.: NCT04798014; URL: www.clinicaltrials.gov.