PDF(Pubmed)
Abstract：
BACKGROUND: This proof-of-concept retrospective case study investigated whether patient-reported outcomes (PRO) instruments, designed to capture symptomatic adverse event data, could identity a known exposure-response (ER) relationship for safety characterized in an original FDA analysis of an approved anti-cancer agent. PRO instruments have been designed to uniquely quantify the tolerability aspects of exposure-associated symptomatic adverse events. We explored whether standard ER analyses of clinician-reported safety data for symptomatic adverse events could be complemented by ER analysis using PRO data that capture and quantify the tolerability aspects of these same symptomatic adverse events.
METHODS: Exposure-associated adverse event data for diarrhea were analyzed in parallel in 120 patients enrolled in a clinical trial using physician reported Common Terminology Criteria for Adverse Events (CTCAE) and patient-reported symptomatic adverse event data captured by the National Cancer Institute\'s (NCI) PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE) instrument. Comparative ER analyses of diarrhea were conducted using the same dataset. Results from the CTCAE and PRO-CTCAE ER analyses were assessed for consistency with the ER relationship for diarrhea established in the original NDA using a 750-patient dataset. The analysis was limited to the 120-patient subset with parallel CTCAE and PRO-CTCAE assessments.
RESULTS: Within the same 120-patient dataset, ER analysis using dense, longitudinal PRO-CTCAE-derived data was sensitive to identify the known ER relationship for diarrhea, whereas the standard CTCAE based ER analysis was not.
CONCLUSIONS: ER analysis using PRO assessed symptomatic adverse event data may be a sensitive tool to complement traditional ER analysis. Improved identification of relationships for safety, by including quantification of the tolerability aspect of symptomatic adverse events using PRO instruments, may be useful to improve the sensitivity of exposure response analysis to support early clinical trial dosage optimization strategies, where decision making occurs within limited small patient datasets.
METHODS: Exposure-associated adverse event data for diarrhea were analyzed in parallel in 120 patients enrolled in a clinical trial using physician reported Common Terminology Criteria for Adverse Events (CTCAE) and patient-reported symptomatic adverse event data captured by the National Cancer Institute\'s (NCI) PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE) instrument. Comparative ER analyses of diarrhea were conducted using the same dataset. Results from the CTCAE and PRO-CTCAE ER analyses were assessed for consistency with the ER relationship for diarrhea established in the original NDA using a 750-patient dataset. The analysis was limited to the 120-patient subset with parallel CTCAE and PRO-CTCAE assessments.
RESULTS: Within the same 120-patient dataset, ER analysis using dense, longitudinal PRO-CTCAE-derived data was sensitive to identify the known ER relationship for diarrhea, whereas the standard CTCAE based ER analysis was not.
CONCLUSIONS: ER analysis using PRO assessed symptomatic adverse event data may be a sensitive tool to complement traditional ER analysis. Improved identification of relationships for safety, by including quantification of the tolerability aspect of symptomatic adverse events using PRO instruments, may be useful to improve the sensitivity of exposure response analysis to support early clinical trial dosage optimization strategies, where decision making occurs within limited small patient datasets.
摘要：
背景：这项概念验证回顾性案例研究调查了患者报告的结果（PRO）工具是否，旨在捕获有症状的不良事件数据，在FDA对批准的抗癌药的原始分析中，可以确定已知的暴露-反应（ER）与安全性的关系。PRO仪器被设计为唯一地量化暴露相关症状不良事件的耐受性方面。我们探讨了临床医生报告的症状性不良事件安全性数据的标准ER分析是否可以通过使用PRO数据捕获和量化这些相同症状性不良事件的耐受性方面的ER分析来补充。
方法：使用美国国家癌症研究所（NCI）PRO的不良事件通用术语标准（PRO-CTCAE）工具捕获的医生报告的不良事件通用术语标准（CTCAE）和患者报告的不良事件数据，对参加临床试验的120名患者进行平行分析。使用相同的数据集进行腹泻的比较ER分析。使用750名患者的数据集，评估CTCAE和PRO-CTCAEER分析的结果与原始NDA中建立的腹泻的ER关系的一致性。分析仅限于120名患者的子集，并进行平行的CTCAE和PRO-CTCAE评估。
结果：在相同的120名患者数据集中，ER分析使用密集，纵向PRO-CTCAE数据对确定已知的腹泻ER关系敏感，而基于标准CTCAE的ER分析则不是.
结论：使用PRO评估症状不良事件数据的ER分析可能是补充传统ER分析的敏感工具。改进了对安全关系的识别，通过使用PRO仪器对有症状的不良事件的耐受性方面进行量化，可能有助于提高暴露反应分析的敏感性，以支持早期临床试验剂量优化策略，在有限的小患者数据集内进行决策。
方法：使用美国国家癌症研究所（NCI）PRO的不良事件通用术语标准（PRO-CTCAE）工具捕获的医生报告的不良事件通用术语标准（CTCAE）和患者报告的不良事件数据，对参加临床试验的120名患者进行平行分析。使用相同的数据集进行腹泻的比较ER分析。使用750名患者的数据集，评估CTCAE和PRO-CTCAEER分析的结果与原始NDA中建立的腹泻的ER关系的一致性。分析仅限于120名患者的子集，并进行平行的CTCAE和PRO-CTCAE评估。
结果：在相同的120名患者数据集中，ER分析使用密集，纵向PRO-CTCAE数据对确定已知的腹泻ER关系敏感，而基于标准CTCAE的ER分析则不是.
结论：使用PRO评估症状不良事件数据的ER分析可能是补充传统ER分析的敏感工具。改进了对安全关系的识别，通过使用PRO仪器对有症状的不良事件的耐受性方面进行量化，可能有助于提高暴露反应分析的敏感性，以支持早期临床试验剂量优化策略，在有限的小患者数据集内进行决策。
