背景:在过去的几十年里,美国国会使美国食品和药物管理局(FDA)能够促进和加快针对严重疾病的药物开发,并通过五种特殊名称和审查途径满足未满足的医疗需求:孤儿,快速通道,加速审批,优先审查,和突破性治疗。
目的:本研究回顾了FDA关于药物开发安全性的五个特殊名称,疗效/临床获益,临床试验,创新,经济激励,发展时间表,和价格。
方法:我们进行了关键词搜索,以确定分析FDA特殊名称影响的研究(孤儿,快速通道,加速审批,优先审查,和突破性治疗)的安全性,疗效/临床获益,试验,创新,经济激励,发展时代,以及新药的定价。结果在叙述性概述中进行了总结。
结果:加速批准缩短了新药上市时间。然而,更快的药物开发和监管审查与更多未被识别的不良事件和上市后安全性修订相关.支持特殊FDA批准的临床试验经常使用小型,非随机化,开放标签设计。监测未知不良事件所需的批准后试验通常会延迟或甚至不启动。证据表明,在特殊审查途径下批准的药物,销售为“突破”,比获得标准FDA批准的产品更具创新性,并提供更高的临床效益。特殊指定是投资者和制药公司开发医疗需求未得到满足的罕见疾病药物的经济上可行的策略,由于财政激励,加快发展时间表,更高的临床试验成功率,除了更高的价格。尽管如此,病人,医师,保险公司担心在没有证实的好处的情况下花钱购买药物,甚至花钱购买无效的药物。尽管欧洲国家建立了基于绩效和财务的管理进入协议,以解决临床试验证据和成本效益方面的不确定性,这些药物的定价和报销在美国基本上不受监管.
结论:FDA的特殊指定缩短了治疗罕见和严重疾病的新药的临床开发和FDA批准时间。特殊指定药物为患者提供更大的临床益处。然而,医师,病人,保险公司必须意识到,特殊指定药物通常是根据非稳健试验批准的,与更多未被识别的副作用有关,并以更高的价格出售。
BACKGROUND: Over the past decades, US Congress enabled the US Food and Drug Administration (FDA) to facilitate and expedite drug development for serious conditions filling unmet medical needs with five special designations and review pathways: orphan, fast track, accelerated approval, priority review, and breakthrough therapy.
OBJECTIVE: This study reviews the FDA\'s five special designations for drug development regarding their safety, efficacy/clinical benefit, clinical trials, innovation, economic incentives, development timelines, and price.
METHODS: We conducted a keyword search to identify studies analyzing the impact of the FDA\'s special designations (orphan, fast track, accelerated approval, priority review, and breakthrough therapy) on the safety, efficacy/clinical benefit, trials, innovativeness, economic incentives, development times, and pricing of new drugs. Results were summarized in a narrative overview.
RESULTS: Expedited approval reduces new drugs\' time to market. However, faster drug development and regulatory review are associated with more unrecognized adverse events and post-marketing safety revisions. Clinical trials supporting special FDA approvals frequently use small, non-randomized, open-label designs. Required post-approval trials to monitor unknown adverse events are often delayed or not even initiated. Evidence suggests that drugs approved under special review pathways, marketed as \"breakthroughs\", are more innovative and deliver a higher clinical benefit than those receiving standard FDA approval. Special designations are an economically viable strategy for investors and pharmaceutical companies to develop drugs for rare diseases with unmet medical needs, due to financial incentives, expedited development timelines, higher clinical trial success rates, alongside greater prices. Nonetheless, patients, physicians, and insurers are concerned about spending money on drugs without a proven benefit or even on drugs that turn out to be ineffective. While European countries established performance- and financial-based managed entry agreements to account for this uncertainty in clinical trial evidence and cost-effectiveness, the pricing and reimbursement of these drugs remain largely unregulated in the US.
CONCLUSIONS: Special FDA designations shorten clinical development and FDA approval times for new drugs treating rare and severe diseases with unmet medical needs. Special-designated drugs offer a greater clinical benefit to patients. However, physicians, patients, and insurers must be aware that special-designated drugs are often approved based on non-robust trials, associated with more unrecognized side effects, and sold for higher prices.