Meta-analysis

1、Stata在Meta分析中的应用席波席波山东大学公共卫生学院山东大学公共卫生学院系统综述与Meta分析的关系系统综述（systematic review）是一种按照既定纳入标准广泛收集某医疗卫生问题的相关研究，而后严格评价其质量，并进行定量合并分析或定性分析，得出综合结论的研究方法。Meta分析（meta-analysis）是用于比较和综合针对同一科学问题研究结果的统计学方法，其结论是否有意义取决于纳入研究的质量，常用于系统综述中的定量合并分析。为什么进行为什么进行Meta分析？分析？解决结果矛盾增加样本量Meta分析步骤分析步骤选题-Novelty检索文献- (Pubmed and Emba

2、se (or Scopus)根据入选标准选择合格的研究复习每个研究并进行质量评估- (如NOS、Jadad评分)提取信息，填写摘录表，建立数据库绘制森林图-(Stata or Revman)异质性检验(如果有异质性，采用Meta回归或亚组分析探讨来源)亚组分析敏感性分析检验发表偏倚非非RCT研究质量评价研究质量评价The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses.http:/www.ohri.ca/programs/clinical_epide

3、miology/oxford.aspRCT研究质量评价研究质量评价Jadad量表，又称为Jadad评分或牛津评分系统，是独立评价临床试验方法学质量的工具。在类似的评价量表中，Jadad量表的使用最为广泛。Jadad量表由 Alejandro Jadad-Bechara 制定，作为哥伦比亚的一名医生，他还是牛津大学内纳菲尔德麻醉剂部研究减轻疼痛的研究员。Jadad和他的组员在1996年的临床对照试验杂志上发表了一篇有关盲法效应的文章。在该文章的附录中，通过评价，给不同临床试验评分，从最差的0分到最高的5分。Jadad认为随机对照试验是现代医学研究的一大进步，在一本2007年写的一本书中，他说“这

4、是一种最简单，但又最有效、最具有革命性的研究形式”。修改后的修改后的Jadad量表（量表（1-3分视为低质量，分视为低质量，4-7分视为高质量）分视为高质量）例1 为了探讨用Aspirin预防心肌梗塞(MI)后死亡的发生，美国在1976-1988年间进行了7个关于Aspirin预防MI后死亡的研究，其结果见表格，其中6项研究的结果表明Aspirin组与安慰剂组的MI后死亡率的差别无统计学意义，仅1项结果表明Aspirin预防 MI后死亡有效。StudyPublication yearAspirin groupPlacebo groupTotalDeathsTotalDeathsMRC-1197

5、46154962467CDP19767584477164MRC-21979832102850126GASP19793173230938PARIS19808108540652AMIS198022672462257219ISIS-219888587157086001720Forest plot命令: metan death1 live1 death2 live2, or label (namevar=study, yearvar=year) metan death1 live1 death2 live2, or label (namevar=study, yearvar=year) xlab(0.

6、45,1,2.19) metan death1 live1 death2 live2, or label (namevar=study, yearvar=year) xlab(0.45,1,2.19) textsize(150)Overall (I-squared = 39.7%, p = 0.127)MRC-1 (1974)GASP (1979)IDISIS-2 (1988)CDP (1976)MRC-2 (1979)AMIS (1980)PARIS (1980)Study0.90 (0.84, 0.96)0.72 (0.49, 1.06)0.80 (0.49, 1.32)OR (95% C

7、I)0.89 (0.83, 0.97)0.68 (0.46, 1.01)0.80 (0.61, 1.06)1.13 (0.93, 1.37)0.80 (0.55, 1.15)100.003.181.80Weight72.883.105.6810.153.22%0.90 (0.84, 0.96)0.72 (0.49, 1.06)0.80 (0.49, 1.32)OR (95% CI)0.89 (0.83, 0.97)0.68 (0.46, 1.01)0.80 (0.61, 1.06)1.13 (0.93, 1.37)0.80 (0.55, 1.15)100.003.181.80Weight72.

8、883.105.6810.153.22% 1.4512.19Sensitivity analysis命令： generate logor=log(_ES) generate selogor=_selogES metainf logor selogor, eform id(study) random print 0.80 0.90 0.84 0.96 1.02 MRC-1 CDP MRC-2 GASP PARIS AMIS ISIS-2 Study ommited Meta-analysis fixed-effects estimates (exponential form) Publicati

9、on bias命令： metabias logor selogor, graph(begg)Beggs funnel plot with pseudo 95% confidence limits logors.e. of: logor-.50.5例2 Gotzsche收集了有关短程小剂量强的松 VS安慰剂或非甾体抗炎药治疗类风湿性关节炎的7个临床随机对照试验(RCTs)，观察类风湿性关节炎患者的关节压痛指数(rechies index)。First author Publication yearExperimental treatmentControl treatmentNoMe

10、anSDNoMeanSDJasni1968916.28.7938.112.8Dick19702417.682440.713Lee19732130.516.52141.419.8Berry19741213111223.711.1Lee19741814.612.41826.415.1Stenberg1992216.31.72111.12.5Geital19952010.84.72016.37.7Forest plot 命令： metan n1 mean1 sd1 n2 mean2 sd2, label (namevar=study, yearvar=year) random textsize(18

11、0)NOTE: Weights are from random effects analysisOverall (I-squared = 71.7%, p = 0.002)Jasni (1968)Berry (1974)IDGeital (1995)Dick (1970)Lee (1973)Stenberg (1992)Lee (1974)Study-1.34 (-1.87, -0.80)-2.00 (-3.16, -0.85)-0.97 (-1.82, -0.12)SMD (95% CI)-0.86 (-1.51, -0.21)-2.14 (-2.86, -1.43)-0.60 (-1.22

12、, 0.02)-2.25 (-3.03, -1.47)-0.85 (-1.54, -0.17)100.0010.4413.45Weight15.6714.9316.0114.2215.28%-1.34 (-1.87, -0.80)-2.00 (-3.16, -0.85)-0.97 (-1.82, -0.12)SMD (95% CI)-0.86 (-1.51, -0.21)-2.14 (-2.86, -1.43)-0.60 (-1.22, 0.02)-2.25 (-3.03, -1.47)-0.85 (-1.54, -0.17)100.0010.4413.45Weight15.6714.9316

13、.0114.2215.28% 0-3.1603.16Sensitivity analysis命令： metainf _ES _seES, eform id(study) random print 0.13 0.26 0.15 0.45 0.51 Jasni Dick Lee Berry Lee Stenberg Geital Study ommited Meta-analysis random-effects estimates (exponential form) Publication bias命令： metabias _ES _seES, graph(begg)Beggs funnel

14、plot with pseudo 95% confidence limits SMDs.e. of: SMD-3-2-10Source of heterogeneity命令： metareg _ES year n1 n2, wsse(_seES) metan n1 mean1 sd1 n2 mean2 sd2,label (namevar=study, yearvar=year) random textsize(160) by(group_n1)NOTE: Weights are from random effects analysis.Overall (I-squared =

15、71.7%, p = 0.002)Stenberg (1992)Berry (1974)Subtotal (I-squared = 31.6%, p = 0.232)Geital (1995)=20Lee (1974)Dick (1970)IDSubtotal (I-squared = 82.9%, p = 0.001)Lee (1973)Study20Jasni (1968)-1.34 (-1.87, -0.80)-2.25 (-3.03, -1.47)-0.97 (-1.82, -0.12)-1.14 (-1.74, -0.54)-0.86 (-1.51, -0.21)-0.85 (-1.

16、54, -0.17)-2.14 (-2.86, -1.43)SMD (95% CI)-1.44 (-2.27, -0.61)-0.60 (-1.22, 0.02)-2.00 (-3.16, -0.85)100.0014.2213.4539.1715.6715.2814.93Weight60.8316.01%10.44-1.34 (-1.87, -0.80)-2.25 (-3.03, -1.47)-0.97 (-1.82, -0.12)-1.14 (-1.74, -0.54)-0.86 (-1.51, -0.21)-0.85 (-1.54, -0.17)-2.14 (-2.86, -1.43)S

17、MD (95% CI)-1.44 (-2.27, -0.61)-0.60 (-1.22, 0.02)-2.00 (-3.16, -0.85)100.0014.2213.4539.1715.6715.2814.93Weight60.8316.01%10.44 0-3.1603.16例3 探讨MC4R基因多态性与2型糖尿病的关系Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childho

18、od and adult obesity. Science 2007; 316:889894 FTO 肥胖 2型糖尿病 Adjusted for BMIOR=1.03, 95%CI 0.96-1.10, p=0.44OR=1.15, 95%CI 1.09-1.23, p=910-6OR=1.32, 95%CI 1.26-1.39, p=310-26Li H, Kilpelinen TO, Liu C,et al. Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians. Diabetologia. 2012 Apr;55(4):981-95. gene lnor=ln(or) gene lnci1=ln(ci1) gene lnci2=ln(ci2) m