背景:体恤使用是一种为患者提供快速获取尚未批准的药物的系统,但目前在临床试验中。在涉及患有危及生命的疾病且没有替代疗法的患者的情况下,研究药物已被授权用于同情使用。例如,患有高度异质性罕见疾病的患者有资格通过同情使用计划获得治疗援助.这项研究旨在调查在罕见疾病的背景下,同情使用的特点,评估同情使用罕见疾病的疗效和安全性,并分析研究药物的上市批准情况。
方法:通过在Embase上进行搜索来收集病例报告/病例系列的同情使用,PubMed,WebofScience,CNKI和SinoMed,从1991年1月到2022年12月。随后,两名独立审核员对这些报告进行了评估.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,研究药物的名称,它的指示,不良事件,治疗结果,和其他相关数据。
结果:共纳入46项研究,包括2079名患者,平均年龄38.1岁。在46项研究中涉及39种不同的药物。此外,肿瘤是罕见疾病治疗中最常见的体恤治疗领域(23/46,50.0%).关于治疗效果,四项研究报告成功解决了疾病,35项研究观察到患者症状改善。相反,四项研究证明对患者疾病无显著影响。此外,一项研究报告说,同情使用后结果恶化,而2项研究中没有描述疗效。31项研究报告了不良事件(67.4%),因为同情使用,13项研究中没有发生不良事件(28.3%).在其他两项研究中,没有描述是否发生治疗引起的不良事件(TEAE).136例患者(6.5%)有5级不良事件(死亡),其中19例死亡(0.9%)被认为与同情使用有关.此外,33项研究(33/46,71.7%)的研究药物于2023年1月31日获得新药批准.从开始体恤使用到正式批准研究药物的时间延迟为790.5(IQR359-2199.3)天。我们发现在11项研究中,包括9种不同的药物,截至2023年1月31日,一些富有同情心的使用适应症尚未收到监管部门的通知.
结论:本研究系统地阐明了同情治疗罕见疾病的现状。同情使用研究药物是罕见疾病的重要治疗选择。总的来说,富有同情心的使用似乎在罕见疾病的背景下显示出良好的疗效,有相当比例的同情使用药物随后获得上市批准。然而,由于某些纳入研究未涵盖安全性数据,因此无法全面评估用于同情的药物的安全性.因此,有必要建立针对同情心使用的不良事件报告系统.
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.