Huml Raymond A, Collyar Deborah, Antonijevic Zoran, Beckman Robert A, Quek Ruben G W, Ye Jingjing
Syneos Health Clinical Solutions, Morrisville, NC, USA.
Patient Advocates in Research, Danville, CA, USA.
Ther Innov Regul Sci. 2023 Nov;57(6):1136-1147. doi: 10.1007/s43441-023-00570-w. Epub 2023 Aug 24.
Master protocols (MPs) are an important addition to the clinical trial repertoire. As defined by the U.S. Food and Drug Administration (FDA), this term means "a protocol designed with multiple sub-studies, which may have different objectives (goals) and involve coordinated efforts to evaluate one or more investigational drugs in one or more disease subtypes within the overall trial structure." This means we now have a unique, scientifically based MP that describes how a clinical trial will be conducted using one or more potential candidate therapies to treat patients in one or more diseases. Patient engagement (PE) is also a critical factor that has been recognized by FDA through its Patient-Focused Drug Development (PFDD) initiative, and by the European Medicines Agency (EMA), which states on its website that it has been actively interacting with patients since the creation of the Agency in 1995. We propose that utilizing these PE principles in MPs can make them more successful for sponsors, providers, and patients. Potential benefits of MPs for patients awaiting treatment can include treatments that better fit a patient's needs; availability of more treatments; and faster access to treatments. These make it possible to develop innovative therapies (especially for rare diseases and/or unique subpopulations, e.g., pediatrics), to minimize untoward side effects through careful dose escalation practices and, by sharing a control arm, to lower the probability of being assigned to a placebo arm for clinical trial participants. This paper is authored by select members of the American Statistical Association (ASA)/DahShu Master Protocol Working Group (MPWG) People and Patient Engagement (PE) Subteam. DahShu is a 501(c)(3) non-profit organization, founded to promote research and education in data science. This manuscript does not include direct feedback from US or non-US regulators, though multiple regulatory-related references are cited to confirm our observation that improving patient engagement is supported by regulators. This manuscript represents the authors' independent perspective on the Master Protocol; it does not represent the official policy or viewpoint of FDA or any other regulatory organization or the views of the authors' employers. The objective of this manuscript is to provide drug developers, contract research organizations (CROs), third party capital investors, patient advocacy groups (PAGs), and biopharmaceutical executives with a better understanding of how including the patient voice throughout MP development and conduct creates more efficient clinical trials. The PE Subteam also plans to publish a Plain Language Summary (PLS) of this publication for clinical trial participants, patients, caregivers, and the public as they seek to understand the risks and benefits of MP clinical trial participation.
主方案（MPs）是临床试验方法中的一项重要补充。根据美国食品药品监督管理局（FDA）的定义，该术语指“一种设计有多个子研究的方案，这些子研究可能有不同的目标，并涉及协同努力，在整体试验结构内评估一种或多种研究药物在一种或多种疾病亚型中的效果”。这意味着我们现在有了一个独特的、基于科学的主方案，它描述了如何使用一种或多种潜在的候选疗法在一种或多种疾病中治疗患者来开展临床试验。患者参与（PE）也是一个关键因素，FDA通过其以患者为中心的药物研发（PFDD）倡议认识到了这一点，欧洲药品管理局（EMA）也认识到了这一点，EMA在其网站上表示，自1995年该机构成立以来，一直在积极与患者互动。我们建议在主方案中运用这些患者参与原则，能使其对申办方、医疗服务提供者和患者而言更加成功。对于等待治疗的患者来说，主方案的潜在益处可能包括更符合患者需求的治疗方法；更多治疗方法的可及性；以及更快获得治疗。这些使得开发创新疗法（特别是针对罕见病和/或独特亚群，如儿科患者）成为可能，通过谨慎的剂量递增实践将不良副作用降至最低，并通过共享一个对照臂，降低临床试验参与者被分配到安慰剂组的概率。本文由美国统计协会（ASA）/大树主方案工作组（MPWG）人员与患者参与（PE）子团队的选定成员撰写。大树是一个依据美国国内税收法第501(c)(3)条成立的非营利组织，其成立目的是促进数据科学领域的研究和教育。本手稿未包括来自美国或非美国监管机构的直接反馈，不过引用了多个与监管相关的参考文献，以证实我们的观察结果，即改善患者参与得到了监管机构的支持。本手稿代表了作者对主方案的独立观点；它不代表FDA或任何其他监管组织的官方政策或观点，也不代表作者雇主的观点。本手稿的目的是让药物研发人员、合同研究组织（CRO）、第三方资本投资者、患者权益倡导组织（PAG）以及生物制药企业高管更好地理解在主方案的整个开发和实施过程中纳入患者意见如何能创造出更高效的临床试验。PE子团队还计划为临床试验参与者、患者、护理人员和公众发布本出版物的通俗易懂总结（PLS），因为他们试图了解参与主方案临床试验的风险和益处。
