Abstract：
BACKGROUND: New cancer drugs can be approved by the US Food and Drug Administration (FDA) on the basis of surrogate endpoints while data on overall survival are still incomplete or immature, with too few deaths for meaningful analysis. We aimed to evaluate whether clinical trials with immature survival data generated evidence of overall survival benefit during the period after marketing authorisation, and where that evidence was reported.
METHODS: In this retrospective analysis, we searched Drugs@FDA to identify cancer drug indications approved between Jan 1, 2001, and Dec 31, 2018, on the basis of immature survival data. We systematically collected publicly available data on postapproval overall survival results in labelling (Drugs@FDA), journal publications (MEDLINE via PubMed), and clinical trial registries (ClinicalTrials.gov). The primary outcome was availability of statistically significant overall survival benefits during the period after marketing authorisation (until March 31, 2023). Additionally, we evaluated the availability and timing of overall survival findings in labelling, journal publications, and ClinicalTrials.gov records.
RESULTS: During the study period, the FDA granted marketing authorisation to 223 cancer drug indications, 95 of which had overall survival as an endpoint. 39 (41%) of these 95 indications had immature survival data. After a minimum of 4·3 years of follow-up during the period after marketing authorisation (and median 8·2 years [IQR 5·3-12·0] since FDA approval), additional survival data from the pivotal trials became available in either revised labelling or publications, or both, for 38 (97%) of 39 indications. Additional data on overall survival showed a statistically significant benefit in 12 (32%) of 38 indications, whereas mature data yielded statistically non-significant overall survival findings for 24 (63%) indications. Statistically significant evidence of overall survival benefit was reported in either labelling or publications a median of 1·5 years (IQR 0·8-2·3) after initial approval. The median time to availability of statistically non-significant overall survival results was 3·3 years (2·2-4·5). The availability of overall survival results on ClinicalTrials.gov varied considerably.
CONCLUSIONS: Fewer than a third of indications approved with immature survival data showed a statistically significant overall survival benefit after approval. Notable inconsistencies in timing and availability of information after approval across different sources emphasise the need for better reporting standards.
BACKGROUND: None.
METHODS: In this retrospective analysis, we searched Drugs@FDA to identify cancer drug indications approved between Jan 1, 2001, and Dec 31, 2018, on the basis of immature survival data. We systematically collected publicly available data on postapproval overall survival results in labelling (Drugs@FDA), journal publications (MEDLINE via PubMed), and clinical trial registries (ClinicalTrials.gov). The primary outcome was availability of statistically significant overall survival benefits during the period after marketing authorisation (until March 31, 2023). Additionally, we evaluated the availability and timing of overall survival findings in labelling, journal publications, and ClinicalTrials.gov records.
RESULTS: During the study period, the FDA granted marketing authorisation to 223 cancer drug indications, 95 of which had overall survival as an endpoint. 39 (41%) of these 95 indications had immature survival data. After a minimum of 4·3 years of follow-up during the period after marketing authorisation (and median 8·2 years [IQR 5·3-12·0] since FDA approval), additional survival data from the pivotal trials became available in either revised labelling or publications, or both, for 38 (97%) of 39 indications. Additional data on overall survival showed a statistically significant benefit in 12 (32%) of 38 indications, whereas mature data yielded statistically non-significant overall survival findings for 24 (63%) indications. Statistically significant evidence of overall survival benefit was reported in either labelling or publications a median of 1·5 years (IQR 0·8-2·3) after initial approval. The median time to availability of statistically non-significant overall survival results was 3·3 years (2·2-4·5). The availability of overall survival results on ClinicalTrials.gov varied considerably.
CONCLUSIONS: Fewer than a third of indications approved with immature survival data showed a statistically significant overall survival benefit after approval. Notable inconsistencies in timing and availability of information after approval across different sources emphasise the need for better reporting standards.
BACKGROUND: None.
摘要：
背景：新的癌症药物可以在替代终点的基础上获得美国食品和药物管理局（FDA）的批准，而总生存期的数据仍然不完整或不成熟，死亡人数太少，无法进行有意义的分析。我们的目的是评估不成熟生存数据的临床试验是否在上市许可后的这段时间内产生了总体生存获益的证据。以及证据报告的地方。
方法：在本回顾性分析中，我们在未成熟生存数据的基础上搜索了FDA@Drugs,以确定2001年1月1日至2018年12月31日之间批准的癌症药物适应症.我们系统地收集了有关标签批准后总体生存结果的公开数据（药物@FDA），期刊出版物(MEDLINE通过PubMed)，和临床试验注册(ClinicalTrials.gov)。主要结果是在上市许可后（至2023年3月31日）期间，可获得具有统计学意义的总体生存益处。此外,我们评估了标签中总体生存结果的可用性和时间，期刊出版物,和ClinicalTrials.gov记录。
结果：在研究期间，FDA授予223种癌症药物适应症的上市许可，其中95例以总生存期为终点。这95例适应症中有39例(41%)的生存数据不成熟。在上市许可后的至少4·3年的随访（自FDA批准以来，中位数为8·2年[IQR5·3-12·0]），来自关键试验的其他生存数据可以在修订后的标签或出版物中获得，或者两者兼而有之,39个适应症中的38个（97%）。关于总生存率的其他数据显示，在38个适应症中，有12个（32％）具有统计学上的显着益处。而成熟数据对24例(63%)适应症的总生存结果无统计学意义.在首次批准后的中位数为1·5年（IQR0·8-2·3）的标签或出版物中报告了总体生存获益的统计学显着证据。获得统计学上无统计学意义的总生存结果的中位时间为3·3年（2·2-4·5）。ClinicalTrials.gov上的总体生存结果的可用性差异很大。
结论：在未成熟生存数据中，不到三分之一的适应症在批准后显示出统计学上显著的总体生存获益。在不同来源获得批准后，信息的时间和可用性存在明显的不一致，这强调了需要更好的报告标准。
背景：无。
方法：在本回顾性分析中，我们在未成熟生存数据的基础上搜索了FDA@Drugs,以确定2001年1月1日至2018年12月31日之间批准的癌症药物适应症.我们系统地收集了有关标签批准后总体生存结果的公开数据（药物@FDA），期刊出版物(MEDLINE通过PubMed)，和临床试验注册(ClinicalTrials.gov)。主要结果是在上市许可后（至2023年3月31日）期间，可获得具有统计学意义的总体生存益处。此外,我们评估了标签中总体生存结果的可用性和时间，期刊出版物,和ClinicalTrials.gov记录。
结果：在研究期间，FDA授予223种癌症药物适应症的上市许可，其中95例以总生存期为终点。这95例适应症中有39例(41%)的生存数据不成熟。在上市许可后的至少4·3年的随访（自FDA批准以来，中位数为8·2年[IQR5·3-12·0]），来自关键试验的其他生存数据可以在修订后的标签或出版物中获得，或者两者兼而有之,39个适应症中的38个（97%）。关于总生存率的其他数据显示，在38个适应症中，有12个（32％）具有统计学上的显着益处。而成熟数据对24例(63%)适应症的总生存结果无统计学意义.在首次批准后的中位数为1·5年（IQR0·8-2·3）的标签或出版物中报告了总体生存获益的统计学显着证据。获得统计学上无统计学意义的总生存结果的中位时间为3·3年（2·2-4·5）。ClinicalTrials.gov上的总体生存结果的可用性差异很大。
结论：在未成熟生存数据中，不到三分之一的适应症在批准后显示出统计学上显著的总体生存获益。在不同来源获得批准后，信息的时间和可用性存在明显的不一致，这强调了需要更好的报告标准。
背景：无。
