Department of Medicine, Department of Health Research Methods, Evidence, and Impact; Research Institute of St. Joseph's, McMaster University, Hamilton, Ontario, Canada.
Baim Institute for Clinical Research, Boston, MA, USA.
Nat Cardiovasc Res. 2024 Feb;3(2):110-117. doi: 10.1038/s44161-024-00420-4. Epub 2024 Feb 15.
Phase 3 randomized controlled trials (RCTs), while the gold standard for treatment efficacy and safety, are not always feasible, are expensive, can be prolonged and can be limited in generalizability. Other under-recognized sources of evidence can also help advance drug development. Basic science, proof-of-concept studies and early-phase RCTs can provide evidence regarding the potential for clinical benefit. Real-world evidence generated from registries or observational datasets can provide insights into the treatment of rare diseases that often pose a challenge for trial recruitment. Pragmatic trials embedded in healthcare systems can assess the treatment effects in clinical settings among patient populations sometimes excluded from trials. This Perspective discusses potential sources of evidence that may be used to complement explanatory phase 3 RCTs and to speed the development of new cardiovascular medications. Content is derived from the 19th Global Cardiovascular Clinical Trialists meeting (December 2022), involving clinical trialists, patients, clinicians, regulators, funders and industry representatives.
阶段 3 随机对照试验（RCT）虽然是治疗效果和安全性的金标准，但并非总是可行，成本高昂，耗时较长，且普遍适用性有限。其他未被充分认识的证据来源也有助于推进药物开发。基础科学、概念验证研究和早期阶段 RCT 可以提供有关临床获益潜力的证据。来自登记处或观察性数据集的真实世界证据可以为治疗经常面临试验招募挑战的罕见疾病提供见解。嵌入医疗保健系统中的实用试验可以评估临床试验人群在临床试验中排除的患者人群中的治疗效果。本文观点讨论了可能用于补充解释性阶段 3 RCT 并加速新心血管药物开发的潜在证据来源。内容源自第 19 届全球心血管临床试验学家会议（2022 年 12 月），涉及临床试验学家、患者、临床医生、监管机构、资助者和行业代表。
