Initial and supplementary indication approval of new targeted cancer drugs by the FDA, EMA, Health Canada, and TGA.
Initial and supplementary indication approval of new targeted cancer drugs by the FDA, EMA, Health Canada, and TGA.
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DOI：
10.1007/s10637-022-01227-5
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发表时间：
2022-08
影响因子：
3.4
通讯作者：
Kanavos, Panos
中科院分区：
文献类型：
--
作者：
Michaeli, Daniel Tobias;Mills, Mackenzie;Michaeli, Thomas;Miracolo, Aurelio;Kanavos, Panos
关键词：
背景以前的研究集中在支持新抗癌药物最初获得美国食品和药物管理局（FDA）批准的临床证据上。然而，靶向药物越来越多地被批准用于证据和益处未知的补充适应症。目标.检查支持新靶向抗癌药物在美国、欧盟、加拿大和澳大利亚的初始和补充适应症批准的临床试验证据。数据和方法。2009-2019年间，FDA批准了100种适应症的25种抗癌药物。从FDA、欧洲药品管理局（EMA）、加拿大卫生部（HC）、澳大利亚治疗用品管理局（TGA）和clinicaltrials.gov中提取有关监管批准和临床试验的数据。多变量logistic回归比较了初始和补充适应症批准的特征，报告了调整后的比值比（AOR）和95%置信区间（CI）。结果在100种考虑的癌症适应症中，FDA批准了96种，EMA 92种，HC 86种和TGA 83种（83%，p < 0.05）。FDA比其他机构更频繁地授予优先审查，有条件批准和孤儿药指定。初始批准更有可能获得有条件/加速批准（AOR：2.69，95%CI [1.07-6.77]，p < 0.05），孤儿药（AOR：3.32，95%CI [1.38-8.00]，p < 0.01），优先审查（AOR：2.60，95%CI [1.17-5.78]，p < 0.05），并且是单药治疗（AOR：5.91，95%CI [1.14-30.65]，p < 0.05）。初始适应症的关键性试验往往较短（每月AOR：0.96，95%CI [0.93-0.99]，p < 0.05），低阶段设计（每个临床阶段的AOR：0.28，95%CI [0.09-0.85]，p < 0.05），并招募更多患者（每100例患者的AOR：1.19，95%CI [1.01-1.39]，p < 0.05）。结论.靶向抗癌药物越来越多地被批准用于具有不同临床益处的多种适应症。药物首先被批准作为单一疗法用于治疗需求高度未满足的罕见疾病。虽然加速监管审查激励了这种优先顺序，但适应症特定的安全性，有效性和定价政策是必要的，以反映每个适应症的差异临床和经济价值。在线版本包含补充材料，可通过10.1007/s10637-022-01227-5获得。
Background. Previous research focused on the clinical evidence supporting new cancer drugs’ initial US Food and Drug Administration (FDA) approval. However, targeted drugs are increasingly approved for supplementary indications of unknown evidence and benefit. Objectives. To examine the clinical trial evidence supporting new targeted cancer drugs’ initial and supplementary indication approval in the US, EU, Canada, and Australia. Data and Methods. 25 cancer drugs across 100 indications were identified with FDA approval between 2009–2019. Data on regulatory approval and clinical trials were extracted from the FDA, European Medicines Agency (EMA), Health Canada (HC), Australian Therapeutic Goods Administration (TGA), and clinicaltrials.gov. Regional variations were compared with χ2-tests. Multivariate logistic regressions compared characteristics of initial and supplementary indication approvals, reporting adjusted odds ratios (AOR) with 95% confidence intervals (CI). Results. Out of 100 considered cancer indications, the FDA approved 96, the EMA 92, HC 86, and the TGA 83 (83%, p < 0.05). The FDA more frequently granted priority review, conditional approval, and orphan designations than other agencies. Initial approvals were more likely to receive conditional / accelerated approval (AOR: 2.69, 95%CI [1.07–6.77], p < 0.05), an orphan designation (AOR: 3.32, 95%CI [1.38–8.00], p < 0.01), be under priority review (AOR: 2.60, 95%CI [1.17–5.78], p < 0.05), and be monotherapies (AOR: 5.91, 95%CI [1.14–30.65], p < 0.05) than supplementary indications. Initial indications’ pivotal trials tended to be shorter (AOR per month: 0.96, 95%CI [0.93–0.99], p < 0.05), of lower phase design (AOR per clinical phase: 0.28, 95%CI [0.09–0.85], p < 0.05), and enroll more patients (AOR per 100 patients: 1.19, 95%CI [1.01–1.39], p < 0.05). Conclusions. Targeted cancer drugs are increasingly approved for multiple indications of varying clinical benefit. Drugs are first approved as monotherapies in rare diseases with a high unmet need. Whilst expedited regulatory review incentivizes this prioritization, indication-specific safety, efficacy, and pricing policies are necessary to reflect each indication’s differential clinical and economic value. The online version contains supplementary material available at 10.1007/s10637-022-01227-5.
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13.8
作者：
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6.2
作者：
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通讯作者：
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影响因子：
4.4
作者：
Mestre-Ferrandiz, Jorge;Zozaya, Neboa;Hidalgo-Vega, Alvaro
通讯作者：
Hidalgo-Vega, Alvaro
DOI：
10.3402/jmahp.v4.30970
发表时间：
2016
期刊：
Journal of market access & health policy
影响因子：
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作者：
Flume M;Bardou M;Capri S;Sola-Morales O;Cunningham D;Levin LA;Touchot N;Payers’ Insight
通讯作者：
Payers’ Insight