Project Orbis is a global initiative that aims to streamline regulatory review processes across international regulators in the USA, Canada, Australia, UK, Israel, Brazil, Singapore, and Switzerland to bring promising cancer drugs to patients earlier. We explored the clinical benefit, time to regulatory approval and health technology assessment recommendations, reimbursement outcomes, and monthly treatment prices of cancer drugs reviewed through this initiative. For this retrospective, comparative analysis, we identified cancer drug approvals reviewed through Project Orbis in the USA, Canada, and the UK between May 1, 2019, and Nov 1, 2023. Approvals of cancer drugs reviewed Project Orbis were extracted from the Food and Drug Administration (FDA) Oncology Centre of Excellence and all other FDA approvals from the Drugs@FDA database. The co-primary outcomes were time of regulatory review, time from regulatory approval to health technology assessment recommendation (England, Scotland, and Canada), reimbursement outcomes, clinical benefit (defined as median gains in progression-free survival and overall survival) between cancer drug approvals reviewed by Project Orbis and other FDA approval processes, and monthly treatment prices. The Wilcoxon rank-sum and Fisher's Exact tests were used to examine statistical significance between approvals reviewed through Project Orbis and other FDA approvals during the same period. Between May 1, 2019 and Nov 1, 2023, 81 (33%) of 244 cancer drugs approved by the FDA were reviewed through Project Orbis. The median overall survival gains were 4·1 months (IQR 3·3–5·1) compared with 2·7 months (2·1–3·9) for other FDA approvals. Similarly, progression-free survival gains were 2·6 months (IQR 1·7–4·9) for Project Orbis compared with 2·6 months (0·6–5·1) for other FDA approvals. Neither overall survival (p=0·11) nor progression-free survival (p=0·44) gains were significantly different between the two cohorts of approvals. Of the 14 UK Medicines and Healthcare products Regulatory Agency (MHRA) approvals reviewed by the Scottish Medicines Consortium (SMC), the agency gave positive recommendations for all 14 (100%). Of the 15 MHRA approvals reviewed by the National Institute for Health and Care Excellence (NICE), the agency gave positive recommendations for six (40%). Of the 49 approvals reviewed by the Canadian Agency for Drugs and Technologies in Health (CADTH), the agency conditionally recommended 44 (90%). The time between regulatory approval to NICE recommendation increased from a median of 137 days (IQR 102–172) in 2021 to 302 days (184–483) in 2023, SMC recommendation increased from 185 days (in 2021 for one drug only) to 368 days (IQR 313–476) in 2023, and CADTH decision increased from 97 days (in 2020 for one drug only) to 202 days (IQR 153–304) in 2023. The median monthly price of approvals reviewed through Project Orbis was US$20 000 per month (IQR 13 000–37 000). Clinical outcomes of Project Orbis were no different than other FDA approvals during the same time, and access, after a successful health technology assessment, was considerably delayed or absent, raising questions about whether Project Orbis participation translates into faster patient access to medicines with high clinical benefit and sustainable costs. Although future challenges might benefit from regulatory harmonisation, the advantages are currently unclear. None.

中文翻译：

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通过 Orbis 项目在美国、加拿大、英格兰和苏格兰审查 FDA 批准的癌症药物的临床效益、报销结果和价格：回顾性比较分析


Orbis 项目是一项全球倡议，旨在简化美国、加拿大、澳大利亚、英国、以色列、巴西、新加坡和瑞士等国际监管机构的监管审查流程，以便更早地将有前景的抗癌药物带给患者。我们探讨了通过该计划审查的癌症药物的临床效益、监管批准时间和卫生技术评估建议、报销结果以及每月治疗价格。在这项回顾性比较分析中，我们确定了 2019 年 5 月 1 日至 2023 年 11 月 1 日期间美国、加拿大和英国通过 Orbis 项目审查的癌症药物审批。Orbis 项目审查的癌症药物批准摘自食品和药物管理局。药物管理局 (FDA) 肿瘤学卓越中心以及 Drugs@FDA 数据库中的所有其他 FDA 批准。共同主要结果是监管审查时间、从监管批准到卫生技术评估建议的时间（英格兰、苏格兰和加拿大）、报销结果、癌症之间的临床获益（定义为无进展生存期和总生存期的中位增益）由 Orbis 项目和其他 FDA 审批流程审查的药物审批，以及每月的治疗价格。 Wilcoxon 秩和检验和 Fisher 精确检验用于检查 Orbis 项目审查的批准与同期 FDA 的其他批准之间的统计显着性。 2019年5月1日至2023年11月1日期间，FDA批准的244种抗癌药物中的81种（33%）通过Orbis项目进行了审查。中位总生存期延长为 4·1 个月 (IQR 3·3–5·1)，而其他 FDA 批准的总生存期为 2·7 个月 (2·1–3·9)。 同样，Orbis 项目的无进展生存期延长了 2·6 个月（IQR 1·7–4·9），而其他 FDA 批准的项目则为 2·6 个月（0·6–5·1）。两组批准的总生存期 (p=0·11) 和无进展生存期 (p=0·44) 的增长均无显着差异。在苏格兰药品联盟 (SMC) 审查的英国药品和保健品监管机构 (MHRA) 批准的 14 项批准中，该机构对所有 14 项批准均给出了积极建议 (100%)。在国家健康与护理卓越研究所 (NICE) 审查的 15 项 MHRA 批准中，该机构对其中 6 项 (40%) 给出了积极建议。在加拿大健康药物和技术管理局 (CADTH) 审查的 49 项批准中，该机构有条件推荐了 44 项 (90%)。监管机构批准到 NICE 推荐之间的时间从 2021 年的中位数 137 天（IQR 102-172）增加到 2023 年的 302 天（184-483），SMC 推荐从 185 天（2021 年仅针对一种药物）增加到 368 天2023 年，CADTH 决策时间从 97 天（2020 年仅针对一种药物）增加到 202 天（IQR 313-476），到 2023 年增加到 202 天（IQR 153-304）。通过 Orbis 项目审查的每月批准价格中位数为 20 美元每月 000（IQR 13 000–37 000）。 Orbis 项目的临床结果与 FDA 同期批准的其他药物没有什么不同，并且在成功的卫生技术评估后，获得药物的机会大大延迟或缺失，这引发了人们对 Orbis 项目的参与是否会转化为患者更快获得具有高临床活性的药物的疑问。效益和可持续成本。尽管未来的挑战可能会受益于监管协调，但其优势目前尚不清楚。没有任何。