In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is...In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is intended to enlarge the expected effect size and thereby increase the power of the study. However, composite endpoints also come along with serious challenges and problems. On the one hand, composite endpoints may lead to difficulties during the planning phase of a trial with respect to the sample size calculation, asthe expected clinical effect of an intervention on the composite endpoint depends on the effects on its single components and their correlations. This may lead to wrong assumptions on the sample size needed. Too optimistic assumptions on the expected effect may lead to an underpowered of the trial, whereas a too conservatively estimated effect results in an unnecessarily high sample size. On the other hand, the interpretation of composite endpoints may be difficult, as the observed effect of the composite does not necessarily reflect the effects of the single components. Therefore the demonstration of the clinical efficacy of a new intervention by exclusively evaluating the composite endpoint may be misleading. The present paper summarizes results and recommendations of the latest research addressing the above mentioned problems in the planning, analysis and interpretation of clinical trials with composite endpoints, thereby providing a practical guidance for users.展开更多
Numerical simulation has been carried out to investigate the major factors affecting the time of composite regeneration due to coupling cerium-based additive and microwave for diesel particulate f3ilter(DPF). Effect o...Numerical simulation has been carried out to investigate the major factors affecting the time of composite regeneration due to coupling cerium-based additive and microwave for diesel particulate f3ilter(DPF). Effect on the composite regeneration time from various factors such as mass flow rate of exhaust gas, temperature of exhaust gas, oxygen concentration of exhaust gas, microwave power and amount of cerium-based additive are investigated. And a mathematical model based on fuzzy least squares support vector machines has been developed to forecast the endpoint of the composite regeneration. The results show that the relative error of endpoint forecasting model of composite regeneration is less than 3.5%, and the oxygen concentration of exhaust gas has the biggest effect on the endpoint of composite regeneration, followed by the mass flow rate of exhaust gas, the microwave power, the temperature of exhaust gas and the amount of cerium-based additive.展开更多
Objective: To create a multidimensional composite outcomes endpoint for gouty arthritis treatment in order to consolidate disparate measures of comparative effectiveness. Methods: One solution is to create a multidime...Objective: To create a multidimensional composite outcomes endpoint for gouty arthritis treatment in order to consolidate disparate measures of comparative effectiveness. Methods: One solution is to create a multidimensional composite endpoint that consolidates the complexity of outcomes into a single scale, as was done in this study. The psychometrics of the multidimensional scale and subgroup differences were investigated. Results: Cronbach’s alpha for the multidimensional composite endpoint created in this study was 0.76, indicating good internal reliability. Similar results were found across age, race, and gender. Removing any single item did not increase Cronbach’s alpha beyond 0.77, indicating that none of the items were interfering with the reliability of the scale. However, a reduction in serum urate levels was not significantly correlated with the overall multidimensional endpoint scale with that variable removed, r = 0.03, p > 0.05. Conclusion: This study demonstrated the feasibility and usefulness of creating a composite multidimensional endpoint for assessing treatment outcomes among individuals with gouty arthritis.展开更多
Recurrent event data are commonly encountered in many scientific fields,including biomedical studies,clinical trials and epidemiological surveys,and many statistical methods have been proposed for their analysis.In th...Recurrent event data are commonly encountered in many scientific fields,including biomedical studies,clinical trials and epidemiological surveys,and many statistical methods have been proposed for their analysis.In this paper,we consider to use a weighted composite endpoint of recurrent and terminal events,which is weighted by the severity of each event,to assess the overall effects of covariates on the two types of events.A flexible additive-multiplicative model incorporating both multiplicative and additive effects on the rate function is proposed to analyze such weighted composite event process,and more importantly,the dependence structure among the recurrent and terminal events is left unspecified.For the estimation,we construct the unbiased estimating equations by virtue of the inverse probability weighting technique,and the resulting estimators are shown to be consistent and asymptotically normal under some mild regularity conditions.We evaluate the finite-sample performance of the proposed method via simulation studies and apply the proposed method to a set of real data arising from a bladder cancer study.展开更多
Objective To explore associations between lipoprotein-associated phospholipase A2(Lp-PLA2)and the risk of cardiovascular events in a Chinese population,with a long-term follow-up.Methods A random sample of 2,031 parti...Objective To explore associations between lipoprotein-associated phospholipase A2(Lp-PLA2)and the risk of cardiovascular events in a Chinese population,with a long-term follow-up.Methods A random sample of 2,031 participants(73.6%males,mean age=60.4 years)was derived from the Asymptomatic Polyvascular Abnormalities Community study(APAC)from 2010 to 2011.Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay(ELISA).The composite endpoint was a combination of first-ever stroke,myocardial infarction(MI)or all-cause death.Lp-PLA2 associations with outcomes were assessed using Cox models.Results The median Lp-PLA2 level was 141.0 ng/m L.Over a median follow-up of 9.1 years,we identified 389 events(19.2%),including 137 stroke incidents,43 MIs,and 244 all-cause deaths.Using multivariate Cox regression,when compared with the lowest Lp-PLA2 quartile,the hazard ratios with95%confidence intervals for developing composite endpoints,stroke,major adverse cardiovascular events,and all-cause death were 1.77(1.24–2.54),1.92(1.03–3.60),1.69(1.003–2.84),and 1.94(1.18–3.18)in the highest quartile,respectively.Composite endpoints in 145(28.6%)patients occurred in the highest quartile where Lp-PLA2(159.0 ng/m L)was much lower than the American Association of Clinical Endocrinologists recommended cut-off point,200 ng/m L.Conclusion Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population.The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.展开更多
目的:探讨沙库巴曲缬沙坦对持续性心房颤动(房颤)导管消融术后中远期预后的影响。方法:回顾性分析我院2019年1月—2022年11月因持续性房颤行导管消融术的患者210例,分为沙库巴曲缬沙坦组(ARNI组,93例)和ACEI/ARB组(117例)。采用1∶1倾...目的:探讨沙库巴曲缬沙坦对持续性心房颤动(房颤)导管消融术后中远期预后的影响。方法:回顾性分析我院2019年1月—2022年11月因持续性房颤行导管消融术的患者210例,分为沙库巴曲缬沙坦组(ARNI组,93例)和ACEI/ARB组(117例)。采用1∶1倾向性匹配评分,比较匹配后两组手术相关参数(手术时间、术式、单圈隔离率、左心房基质、手术前后左心房脉冲压、平均左心房压)、手术并发症、复合终点事件和左心功能指标的差异。结果:倾向性评分后ARNI组和ACEI/ARB组共有72对匹配成功,两组手术时间、单圈隔离率、电复律率、手术前后左心房脉冲压、平均左心房压和术后并发症比较均差异无统计学意义。与ACEI/ARB组相比,ARNI组术后6个月的房颤复发率显著降低(25.00%vs 11.11%,P=0.048),心力衰竭加重比例明显减少(11.11%vs 2.78%,P=0.044);两组心血管死亡率和再住院率比较差异无统计学意义。亚组分析中,基质标测显示,两组存在低电压区域比例比较差异无统计学意义(65.28%vs 72.22%);与ACEI/ARB组相比,ARNI组存在左心房基质不良的患者6个月房颤复发率显著降低(33.33%vs 12.00%,P=0.017)。6个月左心功能和生化指标随访发现,与ACEI/ARB组相比,ARNI组左心房直径(LAD)显著降低[(43.08±6.54) mm vs (40.71±4.50) mm,P=0.017],N末端脑钠肽前体(NT-proBNP)水平显著降低[333.00(121.00,870.00) pg/mL vs 195.00(88.50,429.50) pg/mL,P=0.018],纽约心功能分级显著减小(P=0.025)。多因素logistic回归分析显示,沙库巴曲缬沙坦为左心房基质不良的持续性房颤患者导管消融术后6个月无房颤复发的保护性因素(OR=0.291,95%CI:0.094~0.904,P=0.033)。结论:沙库巴曲缬沙坦可有效减少持续性房颤导管消融术后6个月的复发率,改善其左心功能,获益可能主要来自对左心房不良基质的改善作用。展开更多
文摘In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is intended to enlarge the expected effect size and thereby increase the power of the study. However, composite endpoints also come along with serious challenges and problems. On the one hand, composite endpoints may lead to difficulties during the planning phase of a trial with respect to the sample size calculation, asthe expected clinical effect of an intervention on the composite endpoint depends on the effects on its single components and their correlations. This may lead to wrong assumptions on the sample size needed. Too optimistic assumptions on the expected effect may lead to an underpowered of the trial, whereas a too conservatively estimated effect results in an unnecessarily high sample size. On the other hand, the interpretation of composite endpoints may be difficult, as the observed effect of the composite does not necessarily reflect the effects of the single components. Therefore the demonstration of the clinical efficacy of a new intervention by exclusively evaluating the composite endpoint may be misleading. The present paper summarizes results and recommendations of the latest research addressing the above mentioned problems in the planning, analysis and interpretation of clinical trials with composite endpoints, thereby providing a practical guidance for users.
基金Projects(51176045,51276056)supported by the National Natural Science Foundation of ChinaProject(201208430262)supported by the National Studying Abroad Foundation Project of China
文摘Numerical simulation has been carried out to investigate the major factors affecting the time of composite regeneration due to coupling cerium-based additive and microwave for diesel particulate f3ilter(DPF). Effect on the composite regeneration time from various factors such as mass flow rate of exhaust gas, temperature of exhaust gas, oxygen concentration of exhaust gas, microwave power and amount of cerium-based additive are investigated. And a mathematical model based on fuzzy least squares support vector machines has been developed to forecast the endpoint of the composite regeneration. The results show that the relative error of endpoint forecasting model of composite regeneration is less than 3.5%, and the oxygen concentration of exhaust gas has the biggest effect on the endpoint of composite regeneration, followed by the mass flow rate of exhaust gas, the microwave power, the temperature of exhaust gas and the amount of cerium-based additive.
文摘Objective: To create a multidimensional composite outcomes endpoint for gouty arthritis treatment in order to consolidate disparate measures of comparative effectiveness. Methods: One solution is to create a multidimensional composite endpoint that consolidates the complexity of outcomes into a single scale, as was done in this study. The psychometrics of the multidimensional scale and subgroup differences were investigated. Results: Cronbach’s alpha for the multidimensional composite endpoint created in this study was 0.76, indicating good internal reliability. Similar results were found across age, race, and gender. Removing any single item did not increase Cronbach’s alpha beyond 0.77, indicating that none of the items were interfering with the reliability of the scale. However, a reduction in serum urate levels was not significantly correlated with the overall multidimensional endpoint scale with that variable removed, r = 0.03, p > 0.05. Conclusion: This study demonstrated the feasibility and usefulness of creating a composite multidimensional endpoint for assessing treatment outcomes among individuals with gouty arthritis.
基金the National Natural Science Foundation of China(Grant Nos.11771431,11690015,11926341,11731015,11901128 and 11601097)Key Laboratory of RCSDS,CAS(Grant No.2008DP173182)+2 种基金Natural Science Foundation of Guangdong Province of China(Grant Nos.2018A030310068,2021A1515010044)University Innovation Team Project of Guangdong Province(Grant No.2020WCXTD018)Science and Technology Program of Guangzhou,China(Grant Nos.202102020368,202102010512)。
文摘Recurrent event data are commonly encountered in many scientific fields,including biomedical studies,clinical trials and epidemiological surveys,and many statistical methods have been proposed for their analysis.In this paper,we consider to use a weighted composite endpoint of recurrent and terminal events,which is weighted by the severity of each event,to assess the overall effects of covariates on the two types of events.A flexible additive-multiplicative model incorporating both multiplicative and additive effects on the rate function is proposed to analyze such weighted composite event process,and more importantly,the dependence structure among the recurrent and terminal events is left unspecified.For the estimation,we construct the unbiased estimating equations by virtue of the inverse probability weighting technique,and the resulting estimators are shown to be consistent and asymptotically normal under some mild regularity conditions.We evaluate the finite-sample performance of the proposed method via simulation studies and apply the proposed method to a set of real data arising from a bladder cancer study.
基金supported by the National Natural Science Foundation of China [Grant No. 81973112 and Grant No.9204930002]
文摘Objective To explore associations between lipoprotein-associated phospholipase A2(Lp-PLA2)and the risk of cardiovascular events in a Chinese population,with a long-term follow-up.Methods A random sample of 2,031 participants(73.6%males,mean age=60.4 years)was derived from the Asymptomatic Polyvascular Abnormalities Community study(APAC)from 2010 to 2011.Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay(ELISA).The composite endpoint was a combination of first-ever stroke,myocardial infarction(MI)or all-cause death.Lp-PLA2 associations with outcomes were assessed using Cox models.Results The median Lp-PLA2 level was 141.0 ng/m L.Over a median follow-up of 9.1 years,we identified 389 events(19.2%),including 137 stroke incidents,43 MIs,and 244 all-cause deaths.Using multivariate Cox regression,when compared with the lowest Lp-PLA2 quartile,the hazard ratios with95%confidence intervals for developing composite endpoints,stroke,major adverse cardiovascular events,and all-cause death were 1.77(1.24–2.54),1.92(1.03–3.60),1.69(1.003–2.84),and 1.94(1.18–3.18)in the highest quartile,respectively.Composite endpoints in 145(28.6%)patients occurred in the highest quartile where Lp-PLA2(159.0 ng/m L)was much lower than the American Association of Clinical Endocrinologists recommended cut-off point,200 ng/m L.Conclusion Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population.The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.
文摘目的:探讨沙库巴曲缬沙坦对持续性心房颤动(房颤)导管消融术后中远期预后的影响。方法:回顾性分析我院2019年1月—2022年11月因持续性房颤行导管消融术的患者210例,分为沙库巴曲缬沙坦组(ARNI组,93例)和ACEI/ARB组(117例)。采用1∶1倾向性匹配评分,比较匹配后两组手术相关参数(手术时间、术式、单圈隔离率、左心房基质、手术前后左心房脉冲压、平均左心房压)、手术并发症、复合终点事件和左心功能指标的差异。结果:倾向性评分后ARNI组和ACEI/ARB组共有72对匹配成功,两组手术时间、单圈隔离率、电复律率、手术前后左心房脉冲压、平均左心房压和术后并发症比较均差异无统计学意义。与ACEI/ARB组相比,ARNI组术后6个月的房颤复发率显著降低(25.00%vs 11.11%,P=0.048),心力衰竭加重比例明显减少(11.11%vs 2.78%,P=0.044);两组心血管死亡率和再住院率比较差异无统计学意义。亚组分析中,基质标测显示,两组存在低电压区域比例比较差异无统计学意义(65.28%vs 72.22%);与ACEI/ARB组相比,ARNI组存在左心房基质不良的患者6个月房颤复发率显著降低(33.33%vs 12.00%,P=0.017)。6个月左心功能和生化指标随访发现,与ACEI/ARB组相比,ARNI组左心房直径(LAD)显著降低[(43.08±6.54) mm vs (40.71±4.50) mm,P=0.017],N末端脑钠肽前体(NT-proBNP)水平显著降低[333.00(121.00,870.00) pg/mL vs 195.00(88.50,429.50) pg/mL,P=0.018],纽约心功能分级显著减小(P=0.025)。多因素logistic回归分析显示,沙库巴曲缬沙坦为左心房基质不良的持续性房颤患者导管消融术后6个月无房颤复发的保护性因素(OR=0.291,95%CI:0.094~0.904,P=0.033)。结论:沙库巴曲缬沙坦可有效减少持续性房颤导管消融术后6个月的复发率,改善其左心功能,获益可能主要来自对左心房不良基质的改善作用。
