Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Stopford Building, Oxford Road, Manchester, UK; The Kellgren Centre for Rheumatology, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Stopford Building, Oxford Road, Manchester, UK; The Kellgren Centre for Rheumatology, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Semin Arthritis Rheum. 2024 Aug;67:152463. doi: 10.1016/j.semarthrit.2024.152463. Epub 2024 May 22.
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.
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.
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 real-world 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 Sjögren'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.
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.
分类标准旨在确定同质的患者群体进行研究。我们旨在量化 III 期临床试验在结缔组织疾病（CTD）中对真实人群的代表性。
对所有主要已发表的 CTD Ⅲ期临床试验进行全面综述（clinicaltrials.gov）。将临床试验中最常用的分类标准应用于多中心未选择的 CTD 队列。
共确定了 42 项 CTD 试验，没有混合性结缔组织病（MCTD）或未分化结缔组织病（UCTD）的试验。大多数试验（N=38，90%）要求患者符合其相应疾病的分类标准。有 8 项（19.0%）试验排除了重叠性 CTD 患者，另有两项（4.8%）试验排除了特定的重叠特征，如肺动脉高压。一项研究明确允许重叠综合征。我们的真实世界 CTD 队列包括 391 例患者。由于诊断不合格，UCTD 或 MCTD（91/391，23.3%）患者将被排除在临床试验之外。原发性干燥综合征（pSS）、系统性红斑狼疮（SLE）、系统性硬化症（SSc）或特发性炎症性肌病（IIM）患者中，211/300（70.3%）符合各自诊断的分类标准，24/211（11.4%）符合>1 种 CTD 的标准。基于医生诊断和最严格的试验入选标准，共有 187/391（47.8%）患者符合入选条件。
在未选择的真实世界 CTD 队列中，多达一半的患者因不符合分类标准、重叠特征或缺乏主要疾病的试验而不符合临床试验入选标准。为了解决这种在获得新型疗法方面的不平等，临床试验设计应在 CTD 中不断发展入选标准。
