WS10.06 How representative are clinical trial cohorts of the general cystic fibrosis population? Implications for trial planning

Background: Strict eligibility criteria mean trial cohorts poorly represent clinical populations and reduce the available participant pool. Aims: To identify: • What percentage of our total and modulator ineligible (MI) CF cohorts meet common trials eligibility criteria • Most frequent exclusion reasons Methods: We mapped inclusion/exclusion criteria (excluding genotype) from our site’s active trials onto the records of all our patients with CF, aged 12+, to identify which patients meet the criteria and the reason(s) for ineligibility. Results: 643 patients were identified, of which MI = 31 (4.8%). Only 198 (31%) total & 7(23%) MI patients met these hypothetical criteria. Some patients had multiple exclusion reasons. 219(36%) total & 8(26%) MI patients were excluded due to ppFEV1 ≥90%; 69(11%) total & 6(19%) MI patients due to clinical instability; 65(10%) total and 6(19%) MI patients due to anticipated inability to adhere to protocols; and 55(9%) total and 8(26%) MI patients due to exclusionary microbiology. Conclusions: CF trial cohorts poorly represent our clinical population, which likely reflects populations in other countries with modulator access. More sensitive primary outcome measures such as MBW may allow patients with higher FEV1 into trials. Extending FEV1 inclusion to 100% would have added 219 patients, including 8 MI. This might be the best strategy to increase the number of eligible patients and make cohorts more representative. Other approaches include considering whether exclusion based on ‘pathogens associated with rapid decline’ should focus on clinical picture rather than just culture results, and planning longer recruitment windows to allow return to clinical stability after an exacerbation. There are very low numbers of MI patients who meet the common inclusion/exclusion criteria. As gene/mRNA therapy trials are likely to enrol this population, opening sufficient sites and establishing networked trial delivery seem vital to meet recruitment targets.