Abstract：
OBJECTIVE: It is unknown whether and to what degree trials submitted to the US FDA to support drug approval adhere to NCCN guideline-recommended care in their baseline and surveillance CNS imaging protocols.
OBJECTIVE: We sought to characterize the frequency with which the trials cited in US FDA drug approvals for first line advanced NSCLC between 2015 and 2020 deviated from NCCN guideline-recommended care for baseline and surveillance CNS imaging.
METHODS: Retrospective observational analysis using publicly available data of (1) list of trials cited by the FDA in drug approvals for first line advanced NSCLC from 2015 to 2020 (2) individual trial protocols (3) published trial data and supplementary appendices (4) archived versions of the NCCN guidelines for NSCLC from 2009 to 2018 (the years during which the trials were enrolling).
METHODS: Estimated percentage of trials for first line advanced NSCLC leading to FDA approval which deviated from NCCN guideline-recommended care with regards to CNS baseline and surveillance imaging.
RESULTS: A total of 14 studies that had been cited in FDA drug approvals for first line advanced NSCLC met our inclusion criteria between January 1, 2015 and September 30, 2020. Of these trials, 8 (57.1%) deviated from NCCN guidelines in their baseline CNS imaging requirement. The frequency of re-assessment of CNS disease was variable amongst trials as well, with 9 (64.3%) deviating from NCCN recommendations.
CONCLUSIONS: The trials supporting US FDA drug approvals in first line advanced NSCLC often have CNS imaging requirements that do not adhere to NCCN guidelines. Many trials permit alternative, substandard methods and the proportion of patients undergoing each modality is uniformly not reported. Nonstandard CNS surveillance protocols are common. To best serve patients with advanced NSCLC in the US, drug approvals by the FDA must be based on trials that mirror clinical practice and have imaging requirements consistent with current US standard of care.
OBJECTIVE: We sought to characterize the frequency with which the trials cited in US FDA drug approvals for first line advanced NSCLC between 2015 and 2020 deviated from NCCN guideline-recommended care for baseline and surveillance CNS imaging.
METHODS: Retrospective observational analysis using publicly available data of (1) list of trials cited by the FDA in drug approvals for first line advanced NSCLC from 2015 to 2020 (2) individual trial protocols (3) published trial data and supplementary appendices (4) archived versions of the NCCN guidelines for NSCLC from 2009 to 2018 (the years during which the trials were enrolling).
METHODS: Estimated percentage of trials for first line advanced NSCLC leading to FDA approval which deviated from NCCN guideline-recommended care with regards to CNS baseline and surveillance imaging.
RESULTS: A total of 14 studies that had been cited in FDA drug approvals for first line advanced NSCLC met our inclusion criteria between January 1, 2015 and September 30, 2020. Of these trials, 8 (57.1%) deviated from NCCN guidelines in their baseline CNS imaging requirement. The frequency of re-assessment of CNS disease was variable amongst trials as well, with 9 (64.3%) deviating from NCCN recommendations.
CONCLUSIONS: The trials supporting US FDA drug approvals in first line advanced NSCLC often have CNS imaging requirements that do not adhere to NCCN guidelines. Many trials permit alternative, substandard methods and the proportion of patients undergoing each modality is uniformly not reported. Nonstandard CNS surveillance protocols are common. To best serve patients with advanced NSCLC in the US, drug approvals by the FDA must be based on trials that mirror clinical practice and have imaging requirements consistent with current US standard of care.
摘要：
目的：目前尚不清楚试验是否以及在何种程度上提交给美国FDA以支持药物批准，在其基线和监测CNS成像方案中遵守NCCN指南推荐的护理。
目的：我们试图描述2015年至2020年间美国FDA批准的一线晚期NSCLC药物中引用的试验偏离NCCN指南推荐的基线和监测中枢神经系统成像的频率。
方法：使用以下公开数据进行回顾性观察分析：（1）FDA在2015年至2020年一线晚期NSCLC药物批准中引用的试验清单（2）单独试验方案（3）已发表的试验数据和补充附录（4）2009年至2018年（试验注册的年份）NSCLCNCCN指南的存档版本。
方法：导致FDA批准的一线晚期NSCLC试验的估计百分比偏离了NCCN关于CNS基线和监测成像的指南推荐治疗。
结果：2015年1月1日至2020年9月30日，FDA一线晚期NSCLC药物批准中引用的14项研究符合我们的纳入标准。在这些试验中,8（57.1％）在基线CNS成像要求方面偏离NCCN指南。中枢神经系统疾病的重新评估频率在试验中也是可变的，9（64.3%）偏离NCCN建议。
结论：支持美国FDA批准一线晚期NSCLC药物的试验通常具有不符合NCCN指南的CNS成像要求。许多试验允许替代，不合格的方法和接受每种模式的患者比例均未报告。非标准CNS监测方案是常见的。为了最好地服务于美国晚期非小细胞肺癌患者，FDA的药物批准必须基于反映临床实践的试验,并且影像学要求与美国现行治疗标准一致.
目的：我们试图描述2015年至2020年间美国FDA批准的一线晚期NSCLC药物中引用的试验偏离NCCN指南推荐的基线和监测中枢神经系统成像的频率。
方法：使用以下公开数据进行回顾性观察分析：（1）FDA在2015年至2020年一线晚期NSCLC药物批准中引用的试验清单（2）单独试验方案（3）已发表的试验数据和补充附录（4）2009年至2018年（试验注册的年份）NSCLCNCCN指南的存档版本。
方法：导致FDA批准的一线晚期NSCLC试验的估计百分比偏离了NCCN关于CNS基线和监测成像的指南推荐治疗。
结果：2015年1月1日至2020年9月30日，FDA一线晚期NSCLC药物批准中引用的14项研究符合我们的纳入标准。在这些试验中,8（57.1％）在基线CNS成像要求方面偏离NCCN指南。中枢神经系统疾病的重新评估频率在试验中也是可变的，9（64.3%）偏离NCCN建议。
结论：支持美国FDA批准一线晚期NSCLC药物的试验通常具有不符合NCCN指南的CNS成像要求。许多试验允许替代，不合格的方法和接受每种模式的患者比例均未报告。非标准CNS监测方案是常见的。为了最好地服务于美国晚期非小细胞肺癌患者，FDA的药物批准必须基于反映临床实践的试验,并且影像学要求与美国现行治疗标准一致.
