PDF(Pubmed)
Abstract：
UNASSIGNED: Response Evaluation Criteria in Solid Tumors (RECIST) are commonly used to assess therapeutic response in clinical trials but not in routine care; thus, RECIST-based end points are difficult to include in observational studies. Clinician-anchored approaches for measuring clinical response have been validated but not widely compared with clinical trial data, limiting their use as evidence for clinical decision-making.
UNASSIGNED: To compare response- and progression-based end points in clinical trial and observational cohorts of patients with non-small cell lung cancer (NSCLC).
UNASSIGNED: This retrospective cohort study used patient-level data from the IMpower132 trial (conducted April 7, 2016, to May 31, 2017) and a nationwide electronic health record (EHR)-derived deidentified database (data collected January 1, 2011, to March 31, 2022). Patients in the observational cohort were selected according to the inclusion and exclusion criteria of the IMpower132 trial. All patients in the observational cohort had stage IV NSCLC.
UNASSIGNED: All patients were randomized to or received first-line carboplatin or cisplatin plus pemetrexed.
UNASSIGNED: End points included response rates, duration of response, and progression-free survival, compared between the trial and observational cohorts before and after weighting. Response rates for the observational cohort were derived from the EHR.
UNASSIGNED: A total of 769 patients met inclusion criteria, 494 in the observational cohort (median [IQR] age, 67 [60-74] years; 228 [46.2%] female; 45 [9.1%] Black or African American; 352 [71.3%] White; 53 [10.7%] American Indian or Alaska Native, Asian, Hawaiian or Pacific Islander, or multiracial) and 275 in the trial cohort (median [IQR] age, 63 [56-68] years; 90 [32.7%] female; 4 [1.5%] Black or African American; 194 [70.5%] White; 65 [23.6%] American Indian or Alaska Native, Asian, Hawaiian or Pacific Islander, or multiracial). All 3 end points were comparable between the study cohorts. Trial patients had a higher number of response assessments compared with patients in the weighted observational cohort. The EHR-derived response rate was numerically higher than the objective response rate after weighting (100.3 of 249.3 [40.2%] vs 105 of 275 [38.2%]) due to higher rates of observed partial response than RECIST-based partial response. Among patients with at least 1 response assessment, the EHR-derived response rate remained higher than the objective response rate (100.3 of 193.4 [51.9%] vs 105 of 256 [41.0%]) due to a higher proportion of patients in the observational cohort with no response assessment.
UNASSIGNED: In this study, response- and progression-based end points were similar between clinical trial and weighted observational cohorts, which increases confidence in the reliability of observational end points and can inform their interpretation in relation to trial end points. Additionally, the difference observed in response rates (including vs excluding patients with no response assessment) highlights the importance of future research adopting this 2-way approach when evaluating the relationship of EHR-derived and objective response rates.
UNASSIGNED: To compare response- and progression-based end points in clinical trial and observational cohorts of patients with non-small cell lung cancer (NSCLC).
UNASSIGNED: This retrospective cohort study used patient-level data from the IMpower132 trial (conducted April 7, 2016, to May 31, 2017) and a nationwide electronic health record (EHR)-derived deidentified database (data collected January 1, 2011, to March 31, 2022). Patients in the observational cohort were selected according to the inclusion and exclusion criteria of the IMpower132 trial. All patients in the observational cohort had stage IV NSCLC.
UNASSIGNED: All patients were randomized to or received first-line carboplatin or cisplatin plus pemetrexed.
UNASSIGNED: End points included response rates, duration of response, and progression-free survival, compared between the trial and observational cohorts before and after weighting. Response rates for the observational cohort were derived from the EHR.
UNASSIGNED: A total of 769 patients met inclusion criteria, 494 in the observational cohort (median [IQR] age, 67 [60-74] years; 228 [46.2%] female; 45 [9.1%] Black or African American; 352 [71.3%] White; 53 [10.7%] American Indian or Alaska Native, Asian, Hawaiian or Pacific Islander, or multiracial) and 275 in the trial cohort (median [IQR] age, 63 [56-68] years; 90 [32.7%] female; 4 [1.5%] Black or African American; 194 [70.5%] White; 65 [23.6%] American Indian or Alaska Native, Asian, Hawaiian or Pacific Islander, or multiracial). All 3 end points were comparable between the study cohorts. Trial patients had a higher number of response assessments compared with patients in the weighted observational cohort. The EHR-derived response rate was numerically higher than the objective response rate after weighting (100.3 of 249.3 [40.2%] vs 105 of 275 [38.2%]) due to higher rates of observed partial response than RECIST-based partial response. Among patients with at least 1 response assessment, the EHR-derived response rate remained higher than the objective response rate (100.3 of 193.4 [51.9%] vs 105 of 256 [41.0%]) due to a higher proportion of patients in the observational cohort with no response assessment.
UNASSIGNED: In this study, response- and progression-based end points were similar between clinical trial and weighted observational cohorts, which increases confidence in the reliability of observational end points and can inform their interpretation in relation to trial end points. Additionally, the difference observed in response rates (including vs excluding patients with no response assessment) highlights the importance of future research adopting this 2-way approach when evaluating the relationship of EHR-derived and objective response rates.
摘要：
■实体瘤的反应评估标准（RECIST）通常用于评估临床试验中的治疗反应，但不用于常规护理；因此，基于RECIST的终点难以纳入观察性研究。用于测量临床反应的临床医师锚定方法已得到验证，但未与临床试验数据进行广泛比较。限制它们作为临床决策证据的使用。
比较非小细胞肺癌（NSCLC）患者临床试验和观察队列中基于反应和进展的终点。
这项回顾性队列研究使用了IMpower132试验（2016年4月7日至2017年5月31日进行）的患者水平数据和一个全国性的电子健康记录（EHR）衍生的去识别数据库（2011年1月1日至2022年3月31日收集的数据）。根据IMpower132试验的纳入和排除标准选择观察队列中的患者。观察队列中的所有患者均患有IV期NSCLC。
■所有患者均随机接受或接受一线卡铂或顺铂联合培美曲塞治疗。
■终点包括响应率，响应的持续时间，和无进展生存期，比较研究和观察队列在加权前后.观察性队列的反应率来自EHR。
■共有769名患者符合纳入标准，494在观察性队列中(中位[IQR]年龄，67[60-74]岁;228[46.2％]女性;45[9.1％]黑人或非裔美国人;352[71.3％]白人;53[10.7％]美洲印第安人或阿拉斯加原住民，亚洲人,夏威夷或太平洋岛民，或多种族)和试验队列中的275人(中位[IQR]年龄，63[56-68]年;90[32.7％]女性;4[1.5％]黑人或非裔美国人;194[70.5％]白人;65[23.6％]美洲印第安人或阿拉斯加原住民，亚洲人,夏威夷或太平洋岛民，或多种族)。所有3个终点在研究队列之间具有可比性。与加权观察队列中的患者相比，试验患者的反应评估数量更高。由于观察到的部分反应率高于基于RECIST的部分反应率，因此EHR得出的反应率在数字上高于加权后的客观反应率（249.3的100.3[40.2％]对275的105[38.2％]）。在至少有1次反应评估的患者中，EHR得出的缓解率仍然高于客观缓解率(100.3/193.4[51.9%]vs105/256[41.0%]),这是因为观察队列中无缓解评估的患者比例较高.
■在这项研究中，临床试验和加权观察组之间基于反应和进展的终点相似,这增加了对观察终点可靠性的信心，并可以为它们与试验终点的关系提供信息。此外,观察到的应答率差异(包括与排除无应答评估患者的差异)凸显了未来研究在评估EHR来源的应答率和客观应答率之间的关系时采用这种双向方法的重要性.
比较非小细胞肺癌（NSCLC）患者临床试验和观察队列中基于反应和进展的终点。
这项回顾性队列研究使用了IMpower132试验（2016年4月7日至2017年5月31日进行）的患者水平数据和一个全国性的电子健康记录（EHR）衍生的去识别数据库（2011年1月1日至2022年3月31日收集的数据）。根据IMpower132试验的纳入和排除标准选择观察队列中的患者。观察队列中的所有患者均患有IV期NSCLC。
■所有患者均随机接受或接受一线卡铂或顺铂联合培美曲塞治疗。
■终点包括响应率，响应的持续时间，和无进展生存期，比较研究和观察队列在加权前后.观察性队列的反应率来自EHR。
■共有769名患者符合纳入标准，494在观察性队列中(中位[IQR]年龄，67[60-74]岁;228[46.2％]女性;45[9.1％]黑人或非裔美国人;352[71.3％]白人;53[10.7％]美洲印第安人或阿拉斯加原住民，亚洲人,夏威夷或太平洋岛民，或多种族)和试验队列中的275人(中位[IQR]年龄，63[56-68]年;90[32.7％]女性;4[1.5％]黑人或非裔美国人;194[70.5％]白人;65[23.6％]美洲印第安人或阿拉斯加原住民，亚洲人,夏威夷或太平洋岛民，或多种族)。所有3个终点在研究队列之间具有可比性。与加权观察队列中的患者相比，试验患者的反应评估数量更高。由于观察到的部分反应率高于基于RECIST的部分反应率，因此EHR得出的反应率在数字上高于加权后的客观反应率（249.3的100.3[40.2％]对275的105[38.2％]）。在至少有1次反应评估的患者中，EHR得出的缓解率仍然高于客观缓解率(100.3/193.4[51.9%]vs105/256[41.0%]),这是因为观察队列中无缓解评估的患者比例较高.
■在这项研究中，临床试验和加权观察组之间基于反应和进展的终点相似,这增加了对观察终点可靠性的信心，并可以为它们与试验终点的关系提供信息。此外,观察到的应答率差异(包括与排除无应答评估患者的差异)凸显了未来研究在评估EHR来源的应答率和客观应答率之间的关系时采用这种双向方法的重要性.
