Department of Health Policy, London School of Economics and Political Science, London, United Kingdom.
Program on Regulation, Therapeutics, and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
JAMA Intern Med. 2021 Apr 1;181(4):490-498. doi: 10.1001/jamainternmed.2020.8441.
Numerous cancer drugs have received accelerated approval from the US Food and Drug Administration (FDA) based on clinical trial outcomes that are otherwise not acceptable for traditional FDA approval; the accelerated approval process allows outcomes based on surrogate measures that are only reasonably likely to estimate clinical benefits. In England, the National Institute for Health and Care Excellence (NICE) evaluates the clinical benefits and cost-effectiveness of drugs after they have received regulatory approval and issues recommendations regarding their coverage in the National Health Service (NHS). However, the level of concordance between European and FDA decision-making in the context of drugs qualifying for FDA accelerated approval is unknown.
To compare FDA accelerated approval decisions for cancer drugs with NICE coverage decisions.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study compared cancer drug indications that received FDA accelerated approval from December 11, 1992, to May 31, 2017, with the same set of drug indication pairs in England until August 31, 2019. Data from European Public Assessment Reports developed by the European Medicines Agency (EMA) and public appraisal documents from NICE were used to determine NHS coverage recommendations. National Institute for Health and Care Excellence (NICE) public appraisal documents were analyzed for drug indications, characteristics of clinical evidence, cost-effectiveness, and coverage decisions. Data were analyzed from September 1 to December 31, 2019.
Cancer drug indication coverage decision by NICE.
From 1992 to 2017, 93 cancer drug indications received FDA accelerated approval, 6 of which were subsequently withdrawn, leaving 87 cancer drug indications on the market. As of August 2019, 5 of these indications had been withdrawn or denied market authorization for the European Union by the EMA. From the cohort of EMA-approved drugs, an additional 7 drug indications were not recommended by NICE and were not deemed to have sufficient clinical benefits or cost-effectiveness to warrant mandatory public coverage in England; 5 drugs were not recommended based on clinical benefit and cost-effectiveness criteria, and 2 drugs were not recommended based on cost-effectiveness criteria alone. In total, 12 drug indications were not recommended for public coverage in the NHS, and an additional 30 drug indications were not reviewed by either the EMA (14 drug indications) or NICE (16 drug indications) by the study end date. Most drug indications recommended by NICE were conditional on the negotiation of additional confidential discounts, the imposition of restricted indications that limited prescribing to specific patient subgroups, or the collection of additional data. Among the 9 drug indications with evidence of overall survival benefit at the time of NICE review, 2 were not recommended for public funding based on cost-effectiveness criteria.
In this cohort study, 30 cancer drug indications that were granted accelerated approval by the FDA were not subsequently reviewed by either European regulators or NICE, and 12 drugs were denied authorization or coverage owing to insufficient safety, clinical efficacy, or cost-effectiveness. National Health Service coverage of cancer drugs given FDA accelerated approval commonly required additional price concessions, restrictions to approved indications, or review of additional data.
许多癌症药物已通过美国食品和药物管理局（FDA）的加速审批获得批准，依据的是其他情况下不符合传统 FDA 批准的临床试验结果；加速审批程序允许使用仅合理可能估计临床获益的替代指标的结果。在英国，国家卫生与保健卓越研究所（NICE）在药物获得监管批准后评估其临床获益和成本效益，并就其在国民保健服务（NHS）中的覆盖范围提出建议。然而，在符合 FDA 加速审批标准的药物方面，欧洲和 FDA 决策之间的一致性程度尚不清楚。
比较 FDA 对癌症药物的加速审批决定与 NICE 的覆盖范围决定。
设计、设置和参与者：本回顾性队列研究比较了 1992 年 12 月 11 日至 2017 年 5 月 31 日获得 FDA 加速批准的癌症药物适应证，以及同一组药物适应证对在英格兰直至 2019 年 8 月 31 日的药物适应证对。使用欧洲药品管理局（EMA）制定的欧洲公共评估报告和 NICE 的公共评估文件来确定 NHS 覆盖范围的建议。分析了 NICE 的公共评估文件，以确定药物适应证、临床证据的特征、成本效益和覆盖范围决策。数据分析于 2019 年 9 月 1 日至 12 月 31 日进行。
NICE 对癌症药物适应证的覆盖决策。
1992 年至 2017 年，有 93 种癌症药物获得了 FDA 的加速审批，其中 6 种随后被撤回，市场上仍有 87 种癌症药物。截至 2019 年 8 月，这些适应证中有 5 种已被 EMA 撤回或拒绝在欧盟上市。在 EMA 批准的药物队列中，另有 7 种适应证未被 NICE 推荐，并且被认为没有足够的临床获益或成本效益来保证英国 NHS 的强制性公共覆盖；5 种药物是基于临床获益和成本效益标准不被推荐的，2 种药物仅基于成本效益标准不被推荐。总的来说，有 12 种药物适应证未被推荐用于 NHS 的公共覆盖，另有 30 种药物适应证要么没有被 EMA（14 种药物适应证）审查，要么没有被 NICE（16 种药物适应证）审查。NICE 推荐的大多数药物适应证都需要在谈判额外的保密折扣、限制适应证以限制特定患者亚群的处方，或收集额外的数据。在接受 NICE 审查时具有总体生存获益证据的 9 种药物适应证中，有 2 种基于成本效益标准不被推荐用于公共资金。
在这项队列研究中，30 种获得 FDA 加速审批的癌症药物未被欧洲监管机构或 NICE 审查，有 12 种药物因安全性、临床疗效或成本效益不足而被拒绝授权或覆盖。获得 FDA 加速审批的 NHS 癌症药物的覆盖范围通常需要额外的价格优惠、对批准适应证的限制或额外数据的审查。
