Clinical trials in pulmonary arterial hypertension (PAH) have led to the approval of several effective treatments that improve symptoms, exercise capacity and clinical outcomes. In phase 3 clinical trials, primary end-points must reflect how a patient "feels, functions or survives". In a rare disease like PAH, with an ever-growing number of treatment options and numerous candidate therapies being studied, future clinical trials are now faced with challenges related to sample size requirements, efficiency and demonstration of incremental benefit on traditional end-points in patients receiving background therapy with multiple drugs. Novel clinical trial end-points, innovative trial designs and statistical approaches and new technologies may be potential solutions to tackle the challenges facing future PAH trials, but these must be acceptable to patients and regulatory bodies while preserving methodological rigour. In this World Symposium on Pulmonary Hypertension task force article, we address emerging trial end-points and designs, biomarkers and surrogate end-point validation, the concept of disease modification, challenges and opportunities to address diversity and representativeness, and the use of new technologies such as artificial intelligence in PAH clinical trials.

肺动脉高压 （PAH） 的临床试验已导致几种改善症状、运动能力和临床结果的有效治疗方法获得批准。在 3 期临床试验中，主要终点必须反映患者的“感觉、功能或生存”情况。在像 PAH 这样的罕见疾病中，随着治疗选择的数量不断增加，并且正在研究众多候选疗法，未来的临床试验现在面临着与样本量要求、效率和证明在接受多种药物背景治疗的患者的传统终点上增加益处相关的挑战。新颖的临床试验终点、创新的试验设计和统计方法以及新技术可能是应对未来 PAH 试验所面临挑战的潜在解决方案，但这些必须为患者和监管机构所接受，同时保持方法的严谨性。在这篇世界肺动脉高压研讨会工作组文章中，我们讨论了新兴的试验终点和设计、生物标志物和替代终点验证、疾病改变的概念、解决多样性和代表性的挑战和机遇，以及人工智能等新技术在 PAH 临床试验中的使用。