多个连续性共同终点非劣效临床试验的样本量估计
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摘要
目的针对多个以连续性正态分布变量作为共同终点的非劣效临床试验,探讨保护全局把握度的样本量估计方法。方法在阐明优效性临床试验多个连续性共同终点样本量估计的理论基础上,扩展提出了关于非劣效临床试验多个连续分布共同终点的样本量估计方法。结合临床麻醉学中一个重复测量终点非劣效临床试验的实际案例,基于其预试验的相关结果,在不同的I类错误水平、各重复测量间不同的相关系数、不同的非劣效界值设定下,估计了满足一定的全局把握度(例如80%)的样本量,并借助Monte-Carlo模拟方法对估计结果进行验证。结果本文介绍的非劣效临床试验多个连续性正态分布共同终点的样本量估计方法具有严密的统计理论基础,表明能较好的保护全局把握度,结合实际案例进行的样本量估计结果模拟研究验证了方法的正确性。结论本文为非劣效临床试验多个连续分布共同终点的样本量估计提供了方法学支持,具有较强的实用价值。
Objective To explore a sample size determination that protects overall power in non-inferiority clinical trials with multiple co-primary continuous endpoints.Methods Based on theoretical analysis of the sample size determination with co-primary endpoints in superiority clinical trials,the sample size determination with multiple co-primary continuous endpoints was proposed in non-inferiority clinical trials and was applied in clinical anaesthesiology to estimate the sample size which is repeated measurement.According to pre-experiment,the sample size was estimated to control the overall power(eg.80%) with different levels of the type I error rate,different correlation coefficients and different non-inferiority margins among continuous normal distribution variables.The Monte Carlo simulation method is used to verify the estimation result.Results The sample size determination in co-primary continuous endpoints in non-inferiority clinical trials described in this paper has a strict statistical theory basis and could protect the overall power better which is verified by Monte Carlo simulation with the case study.Conclusion The method in the paper provides methodological support for the sample size determination with co-primary continuous endpoints in a non-inferiority clinical trials which has strong practical value.
Objective To explore a sample size determination that protects overall power in non-inferiority clinical trials with multiple co-primary continuous endpoints.Methods Based on theoretical analysis of the sample size determination with co-primary endpoints in superiority clinical trials,the sample size determination with multiple co-primary continuous endpoints was proposed in non-inferiority clinical trials and was applied in clinical anaesthesiology to estimate the sample size which is repeated measurement.According to pre-experiment,the sample size was estimated to control the overall power(eg.80%) with different levels of the type I error rate,different correlation coefficients and different non-inferiority margins among continuous normal distribution variables.The Monte Carlo simulation method is used to verify the estimation result.Results The sample size determination in co-primary continuous endpoints in non-inferiority clinical trials described in this paper has a strict statistical theory basis and could protect the overall power better which is verified by Monte Carlo simulation with the case study.Conclusion The method in the paper provides methodological support for the sample size determination with co-primary continuous endpoints in a non-inferiority clinical trials which has strong practical value.
引文
[1] Sozu T,Sugimoto T,Hamasaki T,et al.Sample Size Determination in Clinical Trials with Multiple Endpoints.Springer International Publishing,2015,29(21):2169-2179.
[2] Chuang-Stein C,Li JD.Commentary: Changes are still needed on multiple co-primary endpoints: Changes Are Still Needed on Multiple Co-Primary Endpoints.Statistics in Medicine,2017,36(28):4427-4436.
[3] Offen W,Chuang-Stein C,Dmitrienko A,et al.Multiple Co-primary Endpoints: Medical and Statistical Solutions: A Report from the Multiple Endpoints Expert Team of the Pharmaceutical Research and Manufacturers of America.Therapeutic Innovation & Regulatory Science,2007,41(1):31-46.
[4] Committee for Medicinal Products for Human Use.Guideline on Medical Productsfor the Treatment Alzheimer’ Disease and Other Dementias (CPMP/EWP/553/95Rev.1).European Medicines Agency,London,July 24,2008.
[5] Food and Drug Administration.Draft Guidance for Industry.Irritable Bowel Syndrome: Clinical Evaluation of Products for Treatment.Center for Drug Evaluation and Research,Food and Drug Administration,Rockville,MD,March,2010.
[6] Hamasaki T,Evans SR,Asakura K.Design,data monitoring,and analysis of clinical trials with co-primary endpoints: A review.Journal of Biopharmaceutical Statistics,2017,28(1):28-51.
[7] 吴振强,李卫,孙业桓,等.存在共同终点的优效性临床试验样本量问题探讨.中国卫生统计,2013,30(5):680-682.
[8] Sozu T,Sugimoto T,Hamasaki T.Sample size determination in superiority clinical trials with multiple co-primary correlated endpoints.Journal of Biopharmaceutical Statistics,2011,21(4):650-668.
[9] 陈峰,于浩.临床试验精选案例统计学解读.第1版.北京:人民卫生出版社,2015:141-162
[10] 刘玉秀,姚晨,陈峰,等.非劣效性/等效性试验中的统计学分析.中国临床药理学杂志,2000,16(6):448-452.
[11] 陆梦洁,刘玉秀,卢光明,等.单组目标值临床试验多指标时的样本量估计.中国临床药理学与治疗学,2017,22(8):917-921.
[12] 郭正梅,阎小妍,姚晨.两个有序分类变量构建一个分类复合终点指标方法的模拟评价.中国卫生统计,2014,31(2):245-250.
[2] Chuang-Stein C,Li JD.Commentary: Changes are still needed on multiple co-primary endpoints: Changes Are Still Needed on Multiple Co-Primary Endpoints.Statistics in Medicine,2017,36(28):4427-4436.
[3] Offen W,Chuang-Stein C,Dmitrienko A,et al.Multiple Co-primary Endpoints: Medical and Statistical Solutions: A Report from the Multiple Endpoints Expert Team of the Pharmaceutical Research and Manufacturers of America.Therapeutic Innovation & Regulatory Science,2007,41(1):31-46.
[4] Committee for Medicinal Products for Human Use.Guideline on Medical Productsfor the Treatment Alzheimer’ Disease and Other Dementias (CPMP/EWP/553/95Rev.1).European Medicines Agency,London,July 24,2008.
[5] Food and Drug Administration.Draft Guidance for Industry.Irritable Bowel Syndrome: Clinical Evaluation of Products for Treatment.Center for Drug Evaluation and Research,Food and Drug Administration,Rockville,MD,March,2010.
[6] Hamasaki T,Evans SR,Asakura K.Design,data monitoring,and analysis of clinical trials with co-primary endpoints: A review.Journal of Biopharmaceutical Statistics,2017,28(1):28-51.
[7] 吴振强,李卫,孙业桓,等.存在共同终点的优效性临床试验样本量问题探讨.中国卫生统计,2013,30(5):680-682.
[8] Sozu T,Sugimoto T,Hamasaki T.Sample size determination in superiority clinical trials with multiple co-primary correlated endpoints.Journal of Biopharmaceutical Statistics,2011,21(4):650-668.
[9] 陈峰,于浩.临床试验精选案例统计学解读.第1版.北京:人民卫生出版社,2015:141-162
[10] 刘玉秀,姚晨,陈峰,等.非劣效性/等效性试验中的统计学分析.中国临床药理学杂志,2000,16(6):448-452.
[11] 陆梦洁,刘玉秀,卢光明,等.单组目标值临床试验多指标时的样本量估计.中国临床药理学与治疗学,2017,22(8):917-921.
[12] 郭正梅,阎小妍,姚晨.两个有序分类变量构建一个分类复合终点指标方法的模拟评价.中国卫生统计,2014,31(2):245-250.