药物研发的特殊 FDA 认定：孤儿药、快速通道、加速批准、优先审评和突破性疗法。

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. OBJECTIVES: 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. CONCLUSION: 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.

背景：在过去几十年中，美国国会授权美国食品和药物管理局（FDA）通过五个特殊指定和审查途径为严重疾病和未满足的医疗需求开发药物，以促进和加快药物开发：孤儿药、快速通道、加速批准、优先审查和突破性疗法。

目的：本研究回顾了 FDA 对药物开发的五个特殊指定，评估其在安全性、疗效/临床获益、临床试验、创新性、经济激励、开发时间和价格方面的影响。

方法：我们进行了关键字搜索，以确定分析 FDA 特殊指定（孤儿药、快速通道、加速批准、优先审查和突破性疗法）对新药安全性、疗效/临床获益、临床试验、创新性、经济激励、开发时间和定价影响的研究。结果以叙述性综述的形式进行总结。

结果：加速批准缩短了新药的上市时间。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、开放标签设计。用于监测未知不良事件的强制性上市后试验经常被延迟甚至根本没有启动。有证据表明，在特殊审查途径下批准的药物，作为“突破性药物”，比接受标准 FDA 批准的药物更具创新性，能带来更高的临床获益。由于经济激励、加快开发时间表、更高的临床试验成功率以及更高的价格，特殊指定是投资者和制药公司开发治疗罕见病和未满足医疗需求药物的可行经济策略。然而，患者、医生和保险公司担心将资金用于没有临床获益的药物，甚至是无效的药物。尽管欧洲国家制定了基于绩效和财务的管理准入协议，以应对临床试验证据和成本效益方面的不确定性，但这些药物的定价和报销在很大程度上仍未在美国受到监管。

结论：FDA 特殊指定缩短了治疗罕见和严重疾病且未满足医疗需求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了更大的临床获益。然而，医生、患者和保险公司必须意识到，特殊指定药物通常是基于非稳健试验批准的，与更多未被识别的副作用相关，并以更高的价格销售。