ICON plc, Patient-Centered Outcomes, 27 rue de la Villette, 69003, Lyon, France.
Seaton Associates, LLC, 9039 Sligo Creek Parkway #1408, Silver Spring, MD, 20901, USA.
Orphanet J Rare Dis. 2020 Jun 3;15(1):134. doi: 10.1186/s13023-020-01400-0.
Over the past 30 years, the healthcare industry has increasingly turned its attention to rare diseases. Regulators have emphasized the need for clinical research in this area to be patient-centered. However, there is a lack of evidence concerning whether this need is actually met. In this paper, we aim to address this gap.
First, we describe the state of patient-centricity in clinical research in rare diseases based on a targeted literature review. Second, we discuss recommendations from scientific bodies on patient-reported outcome (PRO) measures in rare diseases. Third, we analyze data collected from EMA's and FDA's websites concerning rare disease labeling claims and data from Clinicaltrials.gov concerning the use of PRO measures in rare disease pivotal trials. Fourth, we perform an exhaustive literature review on the use of PRO measures in the pharmaceutical industry, including all phases of clinical research, observational/registry studies, and instrument development and validation.
There is limited information on rare disease patient engagement in study design, recruitment, and retention. None of the initiatives describing methods for developing PRO measures in rare diseases provide the clear guidance clinical researchers need. Only 17.4% of orphan drug labels contain a PRO measure. Less than half of pivotal trials in orphan drugs have a PRO measure as a primary or a secondary endpoint. Although the number of publications about PRO measures in rare diseases has risen in the past fifteen years, our results indicate that substantial improvements are needed to achieve patient-centricity.
The nature and extent of patient engagement in rare disease research is under-documented. The current paradigm for developing and using PRO measures in clinical research is failing to meet the needs of rare disease patients. Not only are PROs rarely used as high-level endpoints in clinical trials or taken into account in labeling claims, they are also under-researched overall - there are too few measures for the multitude of rare diseases. We call for a clear guidance on patient engagement and suggest a realistic approach to the adaptation of PRO strategy to the specific context of clinical research in rare diseases.
在过去的 30 年中，医疗保健行业越来越关注罕见病。监管机构强调需要以患者为中心进行该领域的临床研究。然而，关于这一需求是否得到满足，目前还缺乏证据。本文旨在填补这一空白。
首先，我们根据针对性文献综述描述了罕见病临床研究中以患者为中心的现状。其次，我们讨论了科学机构关于罕见病患者报告结局（PRO）措施的建议。第三，我们分析了 EMA 和 FDA 网站上关于罕见病标签声明的数据以及 Clinicaltrials.gov 上关于在罕见病关键试验中使用 PRO 措施的数据。第四，我们对制药行业中 PRO 措施的使用进行了全面的文献综述，包括临床研究的所有阶段、观察性/登记研究以及仪器的开发和验证。
关于患者在研究设计、招募和保留方面的参与情况，罕见病相关信息有限。没有一项描述开发罕见病 PRO 措施方法的倡议为临床研究人员提供了明确的指导。只有 17.4%的孤儿药标签包含 PRO 措施。在孤儿药的关键试验中，只有不到一半的试验将 PRO 措施作为主要或次要终点。尽管过去十五年中有关罕见病 PRO 措施的出版物数量有所增加，但我们的研究结果表明，需要做出实质性改进才能实现以患者为中心。
罕见病研究中患者参与的性质和程度记录不足。目前在临床研究中开发和使用 PRO 措施的范式未能满足罕见病患者的需求。不仅 PRO 很少作为临床试验的高级终点使用，也很少在标签声明中考虑到它们，而且总体而言，它们的研究也不足——对于众多的罕见病，PRO 措施太少。我们呼吁提供关于患者参与的明确指导，并建议对 PRO 策略进行现实的调整，以适应罕见病临床研究的具体情况。
