Clinical trial eligibility of a real-world connective tissue disease cohort: Results from the LEAP cohort

Introduction: Classification criteria aim to identify a homogenous population of patients for research. We aimed to quantify how well phase -III trials in connective tissue diseases (CTDs) represent a real -world cohort. Methods: A comprehensive review of all major published phase -III trials in CTDs was performed (clinicaltrials. gov). Classification criteria utilised most commonly in clinical trials were applied to a multicentre unselected CTD cohort. Results: There were 42 CTD trials identified, with no trials in mixed (MCTD) or undifferentiated CTD (UCTD). The majority of trials ( N = 38, 90 %) required patients to meet classification criteria for their respective disease. Eight (19.0 %) excluded patients with overlapping CTDs and a further two (4.8 %) excluded specific overlapping features, such as pulmonary arterial hypertension. One study explicitly allowed overlap syndromes. Our realworld CTD cohort included 391 patients. Patients with UCTD or MCTD (91/391, 23.3 %) would be excluded from participation in clinical trials for not having an eligible diagnosis. Of patients with primary Sjo <spacing diaeresis>gren 's syndrome (pSS), SLE, systemic sclerosis (SSc) or idiopathic inflammatory myopathy (IIM), 211/300 (70.3 %) met the classification criteria for their respective diagnosis and 24/211 (11.4 %) met criteria for >1 CTD. In total, 187/391 (47.8 %) would be eligible for recruitment, based upon their physician diagnosis, and most stringent trial eligibility criteria. Conclusion: In an unselected, real -world CTD cohort, up to half of patients are ineligible for clinical trials due to not meeting classification criteria, overlapping features or a lack of trials within their primary disease. To address this inequality in access to novel therapies, clinical trial design should evolve eligibility criteria in CTDs.