Department of Pharmacy and State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital (Dongdan Campus), Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Material Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Orphanet J Rare Dis. 2023 Nov 28;18(1):368. doi: 10.1186/s13023-023-02978-x.
Compassionate use is a system that provides patients with expedited access to drugs which has not yet been approved, but currently in clinical trials. The investigational drugs have been authorized for compassionate use in cases involving patients suffered from life-threatening diseases and with no alternative treatments. For instance, patients afflicted with highly heterogeneous rare diseases are eligible for treatment assistance through the compassionate use program. This study aims to investigate the characteristics of compassionate use in the context of rare diseases, evaluate the efficacy and safety of compassionate use for rare diseases, and analyze the marketing approval of investigational drugs.
The case reports/case series of compassionate use were collected by conducting searches on Embase, PubMed, Web of Science, CNKI and SinoMed, spanning from January 1991 to December 2022. Subsequently, two independent reviewers evaluated these reports. Case reports/case series that met the inclusion criteria and exclusion criteria were enrolled. Information extracted from these reports and series included patients' basic information, the investigational drug's name, its indication, adverse events, treatment outcomes, and other relevant data.
A total of forty-six studies were included, encompassing 2079 patients with an average age of 38.1 years. Thirty-nine different drugs were involved in 46 studies. Furthermore, neoplasms emerged as the most common therapeutic area for compassionate use in rare disease management (23/46, 50.0%). Regarding the treatment efficacy, four studies reported successful disease resolution, while 35 studies observed symptom improvement among patients. Conversely, four studies documented no significant effects on patients' diseases. Moreover, one study reported worsened results following compassionate use, while the efficacy was not described in 2 studies. Adverse events were reported in 31 studies (67.4%) because of the compassionate use, while no adverse events occurred in 13 studies (28.3%). In other 2 studies, there was no description about whether treatment-emergent adverse events (TEAEs) were happened. 136 patients (6.5%) had Grade 5 adverse events (death), of which 19 deaths (0.9%) were considered to be related to compassionate use. Furthermore, the investigational drugs in 33 studies (33/46, 71.7%) received new drug approval at the end of January 31, 2023.The time lag from the start of the compassionate use to the formal approval of the investigational drug was 790.5 (IQR 359-2199.3) days. We found that in 11 studies, encompassing 9 different drugs, some compassionate use indications had not received regulatory authorities at the end of January 31, 2023.
The current status of compassionate use for rare diseases was clarified systematically in this study. Compassionate use of investigational drug is a significant treatment option for rare disease. In general, compassionate use appears to demonstrate favorable efficacy in the context of rare diseases, with a significant proportion of compassionate use drugs subsequently receiving marketing approval. However, the safety of drugs for compassionate use cannot be fully evaluated due to the safety data were not covered in some enrolled studies. Therefore, the establishment of an adverse event reporting system specific to compassionate use is warranted.
同情用药是为那些患有危及生命疾病且无其他替代治疗方法的患者提供加速获得尚未获得批准但目前正在临床试验阶段的药物的一种制度。例如，患有高度异质性罕见病的患者有资格通过同情用药计划获得治疗援助。本研究旨在探讨罕见病背景下同情用药的特点，评估同情用药治疗罕见病的疗效和安全性，并分析试验药物的上市审批情况。
通过对 Embase、PubMed、Web of Science、中国知网和 SinoMed 进行检索，收集 1991 年 1 月至 2022 年 12 月期间的同情用药病例报告/病例系列。随后，由两名独立的评审员对这些报告进行评估。纳入符合纳入标准和排除标准的病例报告/病例系列。从这些报告和系列中提取的信息包括患者的基本信息、试验药物的名称、适应证、不良事件、治疗结果和其他相关数据。
共纳入 46 项研究，包含 2079 名患者，平均年龄为 38.1 岁。39 种不同的药物在 46 项研究中使用。此外，肿瘤是罕见病管理中同情用药最常见的治疗领域（23/46，50.0%）。关于治疗效果，4 项研究报告疾病得到成功缓解，35 项研究观察到患者症状改善。相反，4 项研究记录到药物对患者疾病无显著影响。此外，1 项研究报告同情用药后结果恶化，2 项研究未描述疗效。由于同情用药，31 项研究（67.4%）报告了不良事件，13 项研究（28.3%）未发生不良事件。在另外 2 项研究中，没有描述是否发生了治疗出现的不良事件（TEAEs）。136 名患者（6.5%）发生了 5 级不良事件（死亡），其中 19 例死亡（0.9%）被认为与同情用药有关。此外，在 33 项研究（33/46，71.7%）中，研究药物在 2023 年 1 月 31 日结束时获得了新药批准。从同情用药开始到研究药物正式批准的时间间隔为 790.5（IQR 359-2199.3）天。我们发现，在 11 项研究中，包含 9 种不同的药物，一些同情用药适应证在 2023 年 1 月 31 日结束时尚未获得监管机构的批准。
本研究系统地阐明了罕见病同情用药的现状。试验药物的同情用药是罕见病的一种重要治疗选择。一般来说，同情用药在罕见病中表现出良好的疗效，很大比例的同情用药药物随后获得了上市批准。然而，由于一些纳入的研究未涵盖安全性数据，因此无法充分评估同情用药药物的安全性。因此，有必要建立专门针对同情用药的不良事件报告系统。
