美国FDA批准的抗肿瘤靶向药物早期临床试验设计与研发策略
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摘要
本文通过回顾性分析美国FDA首次批准上市的抗肿瘤靶向药物早期临床研究设计和临床研发策略的特点及趋势,为抗肿瘤靶向新药的早期临床研究设计和临床研发策略的制定提供参考。通过分析2001年1月1日—2017年5月30日期间美国FDA首次批准上市的62个抗肿瘤靶向新药的相关数据,从首次人体试验适应证人群的选择、研究设计、药政申报策略3个角度进行回顾性分析。通过对上述数据的分析,总结出抗肿瘤靶向新药早期临床研究设计与临床研发策略的共性与趋势,并就研究结果对于中国肿瘤创新药的早期开发的意义做阐述。
This paper analyzes retrospectively the characteristics and trends of the design of early clinical trials and clinical development strategies of targeted anticancer drugs which were first approved by the FDA,to provide reference for researchers in this field so as to make more effective targeted anticancer drugs available for clinical therapy faster. The targeted anticancer drugs which were first approved by FDA from January 1 st 2001 to May 30 th 2017 were included in this study. Data analysis was carried out from three aspects: selection of target population,study design,and drug policy declaration strategy. Through analyzing the above data the authors summarized the commonness and tendency of the design of early clinical trials and clinical research development strategy of targetd anticancer drugs and expounded the significance of the research results on early development of innovative anticancer drugs in China.
This paper analyzes retrospectively the characteristics and trends of the design of early clinical trials and clinical development strategies of targeted anticancer drugs which were first approved by the FDA,to provide reference for researchers in this field so as to make more effective targeted anticancer drugs available for clinical therapy faster. The targeted anticancer drugs which were first approved by FDA from January 1 st 2001 to May 30 th 2017 were included in this study. Data analysis was carried out from three aspects: selection of target population,study design,and drug policy declaration strategy. Through analyzing the above data the authors summarized the commonness and tendency of the design of early clinical trials and clinical research development strategy of targetd anticancer drugs and expounded the significance of the research results on early development of innovative anticancer drugs in China.
引文
[1] HAY M,THOMAS DW,CRAIGHEAD JL,et al. Clinical development success rates for investigational drugs[J]. Nat Biotechnol,2014,32(1):40-51.
[2] DIMASI JA,GRABOWSKI HG. Economics of new oncology drug development[J]. J Clin Oncol,2007,25(2):209-216.
[3] TOWNSEND MJ,ARRON JR. Reducing the risk of failure:biomarker-guided trial design[J]. Nat Rev Drug Discov,2016,15(8):517-518.
[4] IASONOS A,O QUIGLEY J. Dose expansion cohorts in phase I trials[J]. Stat Biopharm Res,2016,8(2):161-170.
[5]袁林,邵明立.美国FDA加快新药审评策略以及对我国的启示[J].中国新药杂志,2015,24(21):2401-2404.
[6]张丽杨,颜建周,孙圆圆,等.创新激励视角下的特殊审评与再评价的衔接研究——基于美国经验[J].中国新药杂志,2017,26(22):2625-2630.
[7] U. S. FDA. NDA and BLA Calendar Year Approvals[EB/OL].[2016-11-23]. https://www. fda. gov/Drugs/Development ApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/NDAandBLAApprovalReports/ucm373413. htm.
[8] YIN J,SHEN S. Challenges and innovations in phase I dosefinding designs for molecularly targeted agents and cancer immunotherapies[J]. J Biom Biostat,2016,7(4):pii:324.
[9] WONG KM,CAPASSO A,ECKHARDT SG. The changing landscape of phase I trials in oncology[J]. Nat Rev Clin Oncol,2016,13(2):106-117.
[10] POSTEL-VINAY S,GOMEZ-ROCA C,MOLIFE LR,et al.Phase I trials of molecularly targeted agents:should we pay more attention to late toxicities?[J]. J Clin Oncol,2011,29(13):1728-1735.
[11] BUGANO DDG,HESS K,JARDIM DLF,et al. Use of expansion cohorts in phase I trials and probability of success in phase II for 381 anticancer drugs[J]. Clin Cancer Res,2017,23(15):4020-4026.
[2] DIMASI JA,GRABOWSKI HG. Economics of new oncology drug development[J]. J Clin Oncol,2007,25(2):209-216.
[3] TOWNSEND MJ,ARRON JR. Reducing the risk of failure:biomarker-guided trial design[J]. Nat Rev Drug Discov,2016,15(8):517-518.
[4] IASONOS A,O QUIGLEY J. Dose expansion cohorts in phase I trials[J]. Stat Biopharm Res,2016,8(2):161-170.
[5]袁林,邵明立.美国FDA加快新药审评策略以及对我国的启示[J].中国新药杂志,2015,24(21):2401-2404.
[6]张丽杨,颜建周,孙圆圆,等.创新激励视角下的特殊审评与再评价的衔接研究——基于美国经验[J].中国新药杂志,2017,26(22):2625-2630.
[7] U. S. FDA. NDA and BLA Calendar Year Approvals[EB/OL].[2016-11-23]. https://www. fda. gov/Drugs/Development ApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/NDAandBLAApprovalReports/ucm373413. htm.
[8] YIN J,SHEN S. Challenges and innovations in phase I dosefinding designs for molecularly targeted agents and cancer immunotherapies[J]. J Biom Biostat,2016,7(4):pii:324.
[9] WONG KM,CAPASSO A,ECKHARDT SG. The changing landscape of phase I trials in oncology[J]. Nat Rev Clin Oncol,2016,13(2):106-117.
[10] POSTEL-VINAY S,GOMEZ-ROCA C,MOLIFE LR,et al.Phase I trials of molecularly targeted agents:should we pay more attention to late toxicities?[J]. J Clin Oncol,2011,29(13):1728-1735.
[11] BUGANO DDG,HESS K,JARDIM DLF,et al. Use of expansion cohorts in phase I trials and probability of success in phase II for 381 anticancer drugs[J]. Clin Cancer Res,2017,23(15):4020-4026.