Dexmedetomidine is indicated as a sedative agent in intensive care units(ICUs). While several clinical trials and two meta-analyses have compared this agent with propofol or midazolam, the results were variable depend...Dexmedetomidine is indicated as a sedative agent in intensive care units(ICUs). While several clinical trials and two meta-analyses have compared this agent with propofol or midazolam, the results were variable depending on the specific end-point(e.g., duration of mechanical ventilation, ICU mortality, maintaining a target depth of sedation, incidence of delirium episodes, length of hospital stay). Hence, the effectiveness of this new agent vs the comparators seems to be controversial. Trial sequential analysis(TSA) is a statistical technique that can estimate the optimal, cumulative number of patients that would be needed to generate a conclusive result. We therefore applied a TSA model to the most recent meta-analysis evaluating dexmedetomidine. A total of 10 randomized controlled trials were included in our analysis. According to our results, the comparison of dexmedetomidine vs propofol showed no proof of incremental effectiveness for the end-points of length of ICUs stay and incidence of delirium episodes. In contrast, futility(i.e., proof of no incremental effectiveness) was demonstrated for the end-point of mechanical ventilation. Hence, the results for the comparison of dexmedetomidine vs propofol were inconclusive for the first two end-points; on the other hand, conclusiveness was reached for the third end-point. We conclude that the place of dexmedetomidine in therapy of critically ill patients is very uncertain and further controlled trials are still needed.展开更多
AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 tre...AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 treatments were evaluated:(1) irinotecan(camptothecins);(2) paclitaxel(taxanes class);(3) docetaxel(taxanes);(4) everolimus(mammalian target of rapamycin inhibitors);(5) ramucirumab(vascular endothelial growth factor receptor 2 inhibitors);(6) ramucirumab + paclitaxel. Our methodology was based on standard models of Bayesian network meta-analysis. The reference treatment was best supportive care(BSC). The endpoint was overall survival. Median survival was the outcome measure along with 95% credible intervals. RESULTS: Our search identified a total of 7 randomized controlled trials. These trials included 2298 patients(in 15 treatment arms) in whom a total of 6 active treatments were evaluated as well as BSC. There were 21 head-to-head comparisons(6 direct, 15 indirect). The difference in survival between each of two active treatments(paclitaxel and ramucirumab + paclitaxel) vs BSC was statistically significant, while the other 4 showed no statistical difference. In the 6 head-to-head comparisons between active treatments, no significant survival difference was demonstrated. CONCLUSION: Our results indicate that both paclitaxel monotherapy and ramucirumab + paclitaxel determine a significant prolongation in survival as compared with BSC.展开更多
To evaluate the overall effectiveness of treatments for metastatic colorectal cancer, a meta-regression was undertaken in which randomized studies from 2000 to 2012 were evaluated and the temporal trend for both overa...To evaluate the overall effectiveness of treatments for metastatic colorectal cancer, a meta-regression was undertaken in which randomized studies from 2000 to 2012 were evaluated and the temporal trend for both overall survival(OS) and progression-free survival(PFS) was determined. Our literature search was essentially based on Pub Med but information sources were scanned. Trials were included if a fluoropyrimidine regimen was given to at least one arm and information on PFS and OS was available. Medians for OS and PFS were our end-points. Covariates included temporal trend, arm allocation and Kirsten rat sarcoma status. In analyzing 130 treatment arms identified through our literature search, meta-regression showed an improvement with time for both OS(P < 0.001) and PFS(P < 0.001). The increase in median OS was from 14.9 mo in 2000 to 18.8 mo in 2012. Likewise, the improvement in PFS was from 5.7 to 8.1 mo. Multivariate analysis confirmed these findings. A post-hoc multivariate analysis was focused on patient arms treated with bevacizumab(n = 17) or without bevacizumab(n = 113); the multivariate-adjusted improvement attributable to bevacizumab was 1.66 mo for OS(P = 0.071) and 1.59 mo for PFS(P = 0.002). Overall, our results indicatethat OS and PFS have improved from 2000 to 2012 but the extent of this improvement is small and seems to have quite a questionable clinical relevance.展开更多
In patients with epithelian ovarian cancer who have achieved remission after initial surgery and induction chemotherapy, the role of maintenance chemotherapy is controversial. We carried out a trial-sequential analysi...In patients with epithelian ovarian cancer who have achieved remission after initial surgery and induction chemotherapy, the role of maintenance chemotherapy is controversial. We carried out a trial-sequential analysis that included 4 randomised controlled trials. The end-point was progression at 3 years while the boundary for non-inferiority was set at ±20% in risk ratio. The results of our trial-sequential analysis indicated the futility of maintenance chemotherapy, i.e. proof of no effectiveness. Consequently, no further trials of this type should be performed to assess the effectiveness of this intervention in this clinical condition.展开更多
Evidence-based research is increasingly aimed at differentiating between no proof of difference (failed demonstration of superiority) and proof of no difference (demonstration of equivalence). The latter requires that...Evidence-based research is increasingly aimed at differentiating between no proof of difference (failed demonstration of superiority) and proof of no difference (demonstration of equivalence). The latter requires that equivalence margins are incorporated in the analysis of outcomes. We applied an analysis of equivalence to study the incremental benefit of newer-generation vs early-generation drug-eluting stents (DES) in women receiving percutaneous coronary intervention. The clinical material was derived from published data. Our equivalence testing was focused on the end-point of target-lesion revascularisation (TLR). Results were expressed as rate differences (RDs), while the equivalence margins (±2.9%) were derived from the statistical power calculations of a recent trial. Our results clearly indicated that, in women, there was an equivalent effectiveness between newer-generation and early-generation of DES.展开更多
文摘Dexmedetomidine is indicated as a sedative agent in intensive care units(ICUs). While several clinical trials and two meta-analyses have compared this agent with propofol or midazolam, the results were variable depending on the specific end-point(e.g., duration of mechanical ventilation, ICU mortality, maintaining a target depth of sedation, incidence of delirium episodes, length of hospital stay). Hence, the effectiveness of this new agent vs the comparators seems to be controversial. Trial sequential analysis(TSA) is a statistical technique that can estimate the optimal, cumulative number of patients that would be needed to generate a conclusive result. We therefore applied a TSA model to the most recent meta-analysis evaluating dexmedetomidine. A total of 10 randomized controlled trials were included in our analysis. According to our results, the comparison of dexmedetomidine vs propofol showed no proof of incremental effectiveness for the end-points of length of ICUs stay and incidence of delirium episodes. In contrast, futility(i.e., proof of no incremental effectiveness) was demonstrated for the end-point of mechanical ventilation. Hence, the results for the comparison of dexmedetomidine vs propofol were inconclusive for the first two end-points; on the other hand, conclusiveness was reached for the third end-point. We conclude that the place of dexmedetomidine in therapy of critically ill patients is very uncertain and further controlled trials are still needed.
文摘AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 treatments were evaluated:(1) irinotecan(camptothecins);(2) paclitaxel(taxanes class);(3) docetaxel(taxanes);(4) everolimus(mammalian target of rapamycin inhibitors);(5) ramucirumab(vascular endothelial growth factor receptor 2 inhibitors);(6) ramucirumab + paclitaxel. Our methodology was based on standard models of Bayesian network meta-analysis. The reference treatment was best supportive care(BSC). The endpoint was overall survival. Median survival was the outcome measure along with 95% credible intervals. RESULTS: Our search identified a total of 7 randomized controlled trials. These trials included 2298 patients(in 15 treatment arms) in whom a total of 6 active treatments were evaluated as well as BSC. There were 21 head-to-head comparisons(6 direct, 15 indirect). The difference in survival between each of two active treatments(paclitaxel and ramucirumab + paclitaxel) vs BSC was statistically significant, while the other 4 showed no statistical difference. In the 6 head-to-head comparisons between active treatments, no significant survival difference was demonstrated. CONCLUSION: Our results indicate that both paclitaxel monotherapy and ramucirumab + paclitaxel determine a significant prolongation in survival as compared with BSC.
文摘To evaluate the overall effectiveness of treatments for metastatic colorectal cancer, a meta-regression was undertaken in which randomized studies from 2000 to 2012 were evaluated and the temporal trend for both overall survival(OS) and progression-free survival(PFS) was determined. Our literature search was essentially based on Pub Med but information sources were scanned. Trials were included if a fluoropyrimidine regimen was given to at least one arm and information on PFS and OS was available. Medians for OS and PFS were our end-points. Covariates included temporal trend, arm allocation and Kirsten rat sarcoma status. In analyzing 130 treatment arms identified through our literature search, meta-regression showed an improvement with time for both OS(P < 0.001) and PFS(P < 0.001). The increase in median OS was from 14.9 mo in 2000 to 18.8 mo in 2012. Likewise, the improvement in PFS was from 5.7 to 8.1 mo. Multivariate analysis confirmed these findings. A post-hoc multivariate analysis was focused on patient arms treated with bevacizumab(n = 17) or without bevacizumab(n = 113); the multivariate-adjusted improvement attributable to bevacizumab was 1.66 mo for OS(P = 0.071) and 1.59 mo for PFS(P = 0.002). Overall, our results indicatethat OS and PFS have improved from 2000 to 2012 but the extent of this improvement is small and seems to have quite a questionable clinical relevance.
文摘In patients with epithelian ovarian cancer who have achieved remission after initial surgery and induction chemotherapy, the role of maintenance chemotherapy is controversial. We carried out a trial-sequential analysis that included 4 randomised controlled trials. The end-point was progression at 3 years while the boundary for non-inferiority was set at ±20% in risk ratio. The results of our trial-sequential analysis indicated the futility of maintenance chemotherapy, i.e. proof of no effectiveness. Consequently, no further trials of this type should be performed to assess the effectiveness of this intervention in this clinical condition.
文摘Evidence-based research is increasingly aimed at differentiating between no proof of difference (failed demonstration of superiority) and proof of no difference (demonstration of equivalence). The latter requires that equivalence margins are incorporated in the analysis of outcomes. We applied an analysis of equivalence to study the incremental benefit of newer-generation vs early-generation drug-eluting stents (DES) in women receiving percutaneous coronary intervention. The clinical material was derived from published data. Our equivalence testing was focused on the end-point of target-lesion revascularisation (TLR). Results were expressed as rate differences (RDs), while the equivalence margins (±2.9%) were derived from the statistical power calculations of a recent trial. Our results clearly indicated that, in women, there was an equivalent effectiveness between newer-generation and early-generation of DES.
