Clinical Trial Evidence Supporting US Food and Drug Administration Approval of Novel Cancer Therapies Between 2000 and 2016.
Clinical Trial Evidence Supporting US Food and Drug Administration Approval of Novel Cancer Therapies Between 2000 and 2016.
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DOI：
10.1001/jamanetworkopen.2020.24406
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发表时间：
2020-11-02
影响因子：
13.8
通讯作者：
Hemkens LG
中科院分区：
文献类型：
--
作者：
Ladanie A;Schmitt AM;Speich B;Naudet F;Agarwal A;Pereira TV;Sclafani F;Herbrand AK;Briel M;Martin-Liberal J;Schmid T;Ewald H;Ioannidis JPA;Bucher HC;Kasenda B;Hemkens LG
美国食品和药物管理局批准的新癌症疗法有哪些关于癌症治疗结果的可用数据？在这项 17 年来批准用于 100 种适应症的 92 种新型癌症疗法的有效性比较研究中，44% 的药物批准是基于非随机临床试验的数据。随机临床试验通常报告这些药物与显着的肿瘤反应和延迟进展或死亡时间相关，但总生存期的中位绝对增加仅为 2 个月。这项研究的结果表明，在药物批准时，决策者可以获得的支持数据有限，并且与新抗癌药物相关的总体生存率的增加通常很小。当新的癌症疗法出现时，用于支持药物批准的临床试验证据通常是患者和临床医生可以用于决策的唯一关于益处和危害的信息。各种评估引起了人们对这些数据不确定性的担忧，有必要对美国食品和药物管理局 (FDA) 批准的抗癌药物治疗结果的现有信息进行系统调查。描述 2000 年至 2016 年期间首次批准的所有新抗癌药物在 FDA 批准时可获得的治疗结果的临床试验数据。这项比较有效性研究分析了首次批准用于治疗任何类型癌症的新药的随机临床试验和单臂临床试验。批准包是从 drug@FDA 获得的，这是一个公开数据库，包含在美国批准用于人类使用的药物和生物制品的信息。本研究纳入2000年1月至2016年12月的数据。描述了监管和临床试验特征。对于随机临床试验，计算了所有疗法的总生存期、无进展生存期和肿瘤反应的总结治疗结果，并估计了中位绝对生存期的增加。分别评估肿瘤类型和监管特征。 2000年至2016年间，基于127项临床试验的数据，FDA批准了92种新型抗癌药物用于100个适应症。 127 项临床试验中位数为 191 名参与者（四分位数范围 [IQR]，106-448 名参与者）。总体而言，65 项临床试验（51.2%）是随机的，95 项临床试验（74.8%）是开放标签的。 100个适应症中，44个适应症获得加速批准，42个适应症为血液肿瘤，58个适应症为实体瘤。新药的总生存期平均风险比为 0.77（95% CI，0.73-0.81；I2 = 46%），无进展生存期平均风险比为 0.52（95% CI，0.47-0.57；I2= 88%）。以相对风险表示的中位肿瘤反应为 2.37 (95% CI, 2.00-2.80; I2 = 91%)。中位绝对生存获益为 2.40 个月（IQR，1.25-3.89 个月）。在这项研究中，FDA 药物批准时的可用数据表明，新型癌症疗法与显着的肿瘤反应相关，但中位总生存期仅延长 2.40 个月。 17 年临床试验的批准数据表明，患者和临床医生在进入市场时通常对新型癌症治疗方法的益处了解有限。这项比较有效性研究检查了治疗结果的临床试验数据，这些数据用于支持美国食品和药物管理局批准 2000 年至 2016 年间首次批准的新型癌症疗法。
What are the available data on cancer treatment outcomes for new cancer therapies approved by the US Food and Drug Administration? In this comparative effectiveness study of 92 novel cancer therapies approved for 100 indications over 17 years, 44% of drug approvals were based on data from nonrandomized clinical trials. Randomized clinical trials typically reported that these drugs were associated with substantial tumor responses and delays in the time to progression or death, but the median absolute increase in overall survival was only 2 months. This study’s findings indicate that, at the time of drug approval, limited supporting data are available to decision-makers, and the increase in overall survival associated with new cancer drugs is typically small. Clinical trial evidence used to support drug approval is typically the only information on benefits and harms that patients and clinicians can use for decision-making when novel cancer therapies become available. Various evaluations have raised concern about the uncertainty surrounding these data, and a systematic investigation of the available information on treatment outcomes for cancer drugs approved by the US Food and Drug Administration (FDA) is warranted. To describe the clinical trial data available on treatment outcomes at the time of FDA approval of all novel cancer drugs approved for the first time between 2000 and 2016. This comparative effectiveness study analyzed randomized clinical trials and single-arm clinical trials of novel drugs approved for the first time to treat any type of cancer. Approval packages were obtained from drugs@FDA, a publicly available database containing information on drug and biologic products approved for human use in the US. Data from January 2000 to December 2016 were included in this study. Regulatory and clinical trial characteristics were described. For randomized clinical trials, summary treatment outcomes for overall survival, progression-free survival, and tumor response across all therapies were calculated, and median absolute survival increases were estimated. Tumor types and regulatory characteristics were assessed separately. Between 2000 and 2016, 92 novel cancer drugs were approved by the FDA for 100 indications based on data from 127 clinical trials. The 127 clinical trials included a median of 191 participants (interquartile range [IQR], 106-448 participants). Overall, 65 clinical trials (51.2%) were randomized, and 95 clinical trials (74.8%) were open label. Of 100 indications, 44 indications underwent accelerated approval, 42 indications were for hematological cancers, and 58 indications were for solid tumors. Novel drugs had mean hazard ratios of 0.77 (95% CI, 0.73-0.81; I2 = 46%) for overall survival and 0.52 (95% CI, 0.47-0.57; I2 = 88%) for progression-free survival. The median tumor response, expressed as relative risk, was 2.37 (95% CI, 2.00-2.80; I2 = 91%). The median absolute survival benefit was 2.40 months (IQR, 1.25-3.89 months). In this study, data available at the time of FDA drug approval indicated that novel cancer therapies were associated with substantial tumor responses but with prolonging median overall survival by only 2.40 months. Approval data from 17 years of clinical trials suggested that patients and clinicians typically had limited information available regarding the benefits of novel cancer treatments at market entry. This comparative effectiveness research examines clinical trial data on treatment outcomes used to support US Food and Drug Administration approval of novel cancer therapies that were approved for the first time between 2000 and 2016.
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影响因子：
105.7
作者：
Naci, Huseyin;Davis, Courtney;Booth, Christopher M.
通讯作者：
Booth, Christopher M.
影响因子：
158.5
作者：
Larkin, J.;Chiarion-Sileni, V.;Wolchok, J. D.
通讯作者：
Wolchok, J. D.
DOI：
10.1136/bmj.j4530
发表时间：
2017-10-04
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Davis C;Naci H;Gurpinar E;Poplavska E;Pinto A;Aggarwal A
通讯作者：
Aggarwal A
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N
影响因子：
168.9
作者：
Garon, Edward B.;Ciuleanu, Tudor-Eliade;Perol, Maurice
通讯作者：
Perol, Maurice