Crossover designs are well-known to have major advantages when comparing the effects of various non-curative treatments. We compare efficiencies of several crossover designs along with the Balaam’s design with that o...Crossover designs are well-known to have major advantages when comparing the effects of various non-curative treatments. We compare efficiencies of several crossover designs along with the Balaam’s design with that of a parallel group design pertaining to longitudinal studies where event time can only be measured in discrete time intervals. With equally sized sequences, the parallel group design results in the greater efficiency if the number of time periods is small. However, the crossover and Balaam’s designs tend to be more efficient as the study duration increases. The degree to which these designs add efficiency depends on the baseline hazard function and effect size. Additionally, we incorporate different cost considerations at the subject level when comparing the designs to determine the most cost-efficient design. Researchers might consider the crossover or Balaam’s design more efficient if the duration of the study is long enough, especially if the costs of applying the baseline treatment are higher.展开更多
BACKGROUND：Progression-free survival（PFS）has not been extensively investigated as a surrogate for survival in the firstline treatments of pancreatic cancer.The aim of this review was to evaluate PFS as a potential ...BACKGROUND：Progression-free survival（PFS）has not been extensively investigated as a surrogate for survival in the firstline treatments of pancreatic cancer.The aim of this review was to evaluate PFS as a potential surrogate endpoint for overall survival（OS）in advanced pancreatic cancer in trials comparing poly-chemotherapy to gemcitabine alone.DATA SOURCES： A systematic literature search in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted. The key words included randomized trial, first-line chemotherapy, pancreatic cancer, gemcitabine and poly-chemotherapy. Adjusted weighted linear regression was used to calculate Rs （Spearman＇s rank-order correlation coefficient） between PFS and post-progression survival （PPS） with OS （Rs） and between treatment effects on PFS and OS （RHR）. RESUEFS： A total of 30 trials including 8467 patients met the inclusion criteria. Correlation between the treatment effects on PFS and OS （RHR=0.78） and between the endpoint PFS and OS was high across all studies （Rs=0.75）. The slope of the re- gression line was 0.76±0.26, indicating that an agent produc- ing a 10% risk reduction for PFS will provide a 7.6%±2.6% risk reduction for OS. Correlation between PPS and OS was very strong （Rs=0.71） and accounted for more than 50% of the whole OS variability （R2=0.57）. CONCLUSION： Because of the robust correlation with OS and the potential influence of PPS caused by the second line therapies, it may be justified to consider PFS as a surrogate endpoint in trials evaluating new cytotoxic agents when gemcitabine is the control arm.展开更多
The laparoscopic technique in distal pancreatic resection(LDP) has been widely accepted, and outcome data support the hypothesis that survival is improved,partly due to improved postoperative safety and recovery, thus...The laparoscopic technique in distal pancreatic resection(LDP) has been widely accepted, and outcome data support the hypothesis that survival is improved,partly due to improved postoperative safety and recovery, thus optimizing treatment with adjuvant chemotherapy. But laparoscopic pancreaticoduodenectomy(LPD or Whipple-procedures) has spread more slowly, due to the complexity of the procedure. Surgical safety has been a problem in hospitals with low patient volume, resulting in raised postoperative mortality, requiring careful monitoring of outcome during the surgical learning curve. Robotic assistance is expected to improve surgical safety, but data on long term oncological outcome of laparoscopic Whipple procedures with or without robotic assistance is scarce. Future research should still focus surgical safety, but most importantly long term outcome, recorded as recurrence at maximal follow up or-at best-overall long term survival(OS). Available data show median survival above 2.5 years, five year OS more than 30% after LDP even in series with suboptimal adjuvant chemotherapy. Also after LPD, long term survival is reported equal to or longer than open resection. However, surgical safety during the learning curve of LPD is a problem, which hopefully can be facilitated by robotic assistance. Patient reported outcome should also be an endpoint in future trials, including patients with pancreatic ductal adenocarcinoma.展开更多
文摘Crossover designs are well-known to have major advantages when comparing the effects of various non-curative treatments. We compare efficiencies of several crossover designs along with the Balaam’s design with that of a parallel group design pertaining to longitudinal studies where event time can only be measured in discrete time intervals. With equally sized sequences, the parallel group design results in the greater efficiency if the number of time periods is small. However, the crossover and Balaam’s designs tend to be more efficient as the study duration increases. The degree to which these designs add efficiency depends on the baseline hazard function and effect size. Additionally, we incorporate different cost considerations at the subject level when comparing the designs to determine the most cost-efficient design. Researchers might consider the crossover or Balaam’s design more efficient if the duration of the study is long enough, especially if the costs of applying the baseline treatment are higher.
文摘BACKGROUND：Progression-free survival（PFS）has not been extensively investigated as a surrogate for survival in the firstline treatments of pancreatic cancer.The aim of this review was to evaluate PFS as a potential surrogate endpoint for overall survival（OS）in advanced pancreatic cancer in trials comparing poly-chemotherapy to gemcitabine alone.DATA SOURCES： A systematic literature search in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted. The key words included randomized trial, first-line chemotherapy, pancreatic cancer, gemcitabine and poly-chemotherapy. Adjusted weighted linear regression was used to calculate Rs （Spearman＇s rank-order correlation coefficient） between PFS and post-progression survival （PPS） with OS （Rs） and between treatment effects on PFS and OS （RHR）. RESUEFS： A total of 30 trials including 8467 patients met the inclusion criteria. Correlation between the treatment effects on PFS and OS （RHR=0.78） and between the endpoint PFS and OS was high across all studies （Rs=0.75）. The slope of the re- gression line was 0.76±0.26, indicating that an agent produc- ing a 10% risk reduction for PFS will provide a 7.6%±2.6% risk reduction for OS. Correlation between PPS and OS was very strong （Rs=0.71） and accounted for more than 50% of the whole OS variability （R2=0.57）. CONCLUSION： Because of the robust correlation with OS and the potential influence of PPS caused by the second line therapies, it may be justified to consider PFS as a surrogate endpoint in trials evaluating new cytotoxic agents when gemcitabine is the control arm.
文摘The laparoscopic technique in distal pancreatic resection(LDP) has been widely accepted, and outcome data support the hypothesis that survival is improved,partly due to improved postoperative safety and recovery, thus optimizing treatment with adjuvant chemotherapy. But laparoscopic pancreaticoduodenectomy(LPD or Whipple-procedures) has spread more slowly, due to the complexity of the procedure. Surgical safety has been a problem in hospitals with low patient volume, resulting in raised postoperative mortality, requiring careful monitoring of outcome during the surgical learning curve. Robotic assistance is expected to improve surgical safety, but data on long term oncological outcome of laparoscopic Whipple procedures with or without robotic assistance is scarce. Future research should still focus surgical safety, but most importantly long term outcome, recorded as recurrence at maximal follow up or-at best-overall long term survival(OS). Available data show median survival above 2.5 years, five year OS more than 30% after LDP even in series with suboptimal adjuvant chemotherapy. Also after LPD, long term survival is reported equal to or longer than open resection. However, surgical safety during the learning curve of LPD is a problem, which hopefully can be facilitated by robotic assistance. Patient reported outcome should also be an endpoint in future trials, including patients with pancreatic ductal adenocarcinoma.
文摘总生存期(overall survival,OS)是转移性结直肠癌(metastatic colorectal cancer,m CRC)临床试验的主要研究终点,被认为是"金标准"。因为mCRC患者的OS较十年前有明显延长,OS作为临床试验的主要研究终点和评价疗效都受到挑战。在1999年前的单纯化疗时代,无进展生存期(progression-free survival,PFS)被认为是OS的可靠替代终点,由于有效后线治疗的增加,PFS对OS的影响越来越小,其替代性降低;在含靶向药物方案中,尤其是抗血管生成药物治疗中,PFS和OS的相关性也下降。疾病控制时间(duration of disease control,DDC)和治疗策略失败时间(time to failure of strategy,TFS)等新的研究终点逐步显示替代OS的可能性。文章对以上内容进行综述,希望对临床试验的设计和解读提供参考。
