BACKGROUND Progressive pulmonary fibrosis (PFF) is of substantial interest for novel pharmacotherapy discovery, but little is known about clinical trial eligibility criteria. We evaluated eligibility criteria of PPF randomized controlled trials (RCTs), their representativeness in registry patients, and forced vital capacity (FVC) changes and mortality according to trial eligibility. METHODS A systematic search was used to identify completed and in-progress phase II and III PPF RCTs. Common clinical trial eligibility criteria used in ≥60% of previous PPF RCTs were identified. The most common criteria for PPF used in RCTs ("trial-PPF criteria") and the clinical practice guideline definition of PPF ("guideline-PPF criteria") were both applied to patients enrolled in a prospective multicenter Canadian registry. Common trial eligibility criteria were tested for their frequency and association with health outcomes in registry patients who met trial-PPF and guideline-PPF criteria. RESULTS Ten different definitions of PPF were used in 16 RCTs. At the time of meeting PPF definitions, 50% of 864 patients with trial-PPF and 44% of 408 patients with guideline-PPF met the common trial eligibility criteria. For both definitions, trial-eligible patients had more rapid 1-year FVC decline but better transplant-free survival than trial-ineligible patients. Patients with unclassifiable interstitial lung disease (ILD) had higher proportion of trial exclusion compared to those with connective tissue disease-associated ILD and fibrotic hypersensitivity pneumonitis. Annual FVC decline (trial-PPF: -67 to -21 mL; guideline-PPF: -116 to -41 mL) and 1-year transplant-free survival (trial-PPF: 90.5 to 97.5%; guideline-PPF: 87 to 96.2%) varied in trial-eligible patients across ILD subtypes. CONCLUSIONS Existing RCTs use a variety of definitions for PPF with eligibility criteria that have limited representativeness. FVC decline and transplant-free survival vary according to trial eligibility and ILD subtypes.

中文翻译：

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进行性肺纤维化的药物随机对照试验资格标准的普遍性。


背景进行性肺纤维化 （PFF） 是新型药物治疗发现的重大兴趣，但对临床试验资格标准知之甚少。我们评估了 PPF 随机对照试验 （RCTs） 的合格标准、它们在注册患者中的代表性以及根据试验合格性用力肺活量 （FVC） 变化和死亡率。方法 采用系统检索来确定已完成和正在进行的 II 期和 III 期 PPF RCT。确定了 ≥60% 的既往 PPF RCT 中使用的常见临床试验资格标准。RCT 中使用的 PPF 最常见标准（“试验-PPF 标准”）和 PPF 的临床实践指南定义（“指南-PPF 标准”）均适用于加拿大前瞻性多中心登记处入组的患者。在符合试验 PPF 和指南 PPF 标准的注册患者中，测试了常见试验合格标准的频率和与健康结局的相关性。结果 16 项 RCT 使用了 10 种不同的 PPF 定义。在满足 PPF 定义时，864 名试验 PPF 患者中有 50% 符合 408 名指南-PPF 患者，44 名指南中有 PPF 患者符合通用试验合格标准。对于这两种定义，与不符合试验条件的患者相比，符合试验条件的患者 1 年 FVC 下降更快，但无移植生存率更高。与结缔组织病相关 ILD 和纤维化过敏性肺炎患者相比，无法分类的间质性肺病 （ILD） 患者的试验排除比例更高。在符合试验条件的 ILD 亚型患者中，年无移植生存率（试验 PPF：-67 至 -21 mL;指南 PPF：-116 至 -41 mL）和 1 年无移植生存率（试验 PPF：90.5% 至 97.5%;指南 PPF：87 至 96.2%）存在差异。 结论 现有的 RCT 对 PPF 使用了多种定义，其纳入标准的代表性有限。FVC 下降和无移植生存率因试验合格性和 ILD 亚型而异。