临床试验的Meta分析课件

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,临床试验的Meta分析,542-11-#,*,Statistics 542,Introduction to Clinical TrialsMeta Analysis,临床试验的Meta分析,1,Statistics 542Introduction t,Meta-Analysis,Alternatives?Occasionally,Complementary?Yes,Meta-Analysis,Combination of similar studies using similar subjects and similar treatments and similar outcomes,临床试验的Meta分析,2,Meta-AnalysisAlternatives?,Figure 2,Odds Ratios and 95%Confidence Limits for Various Studies and a Pooled Estimate,临床试验的Meta分析,3,Figure 2Odds Ratios and 95%C,New Method of Analyzing Health Data Stirs Debate by Lawrence K.Altman,Increasing use of a controversial statistical method to evaluate medical therapies and surgical procedures is beginning to affect profoundly the care of pregnant women and patients with cancer,heart disease and many other common conditions.,The method,known as meta-analysis promises to plan an increasingly important role in determining health risks,environmental hazards and national policy on payment for medical care.,Backers say technique can draw big,reliable conclusions from small,inconsistent findings.,Meta-analysis is a term derived from the Greek meaning an analysis that is more comprehensive.The larger numbers obtained by combining studies provide a greater statistical power than any of the individual studies.Researchers are often able to draw more reliable inferences or new conclusions from the combined results than from the smaller studies that may be inconclusive individually.,In earlier applications of meta-analysis,researchers evaluated intelligence quotients,government social welfare programs and many other topics.Meta-analysis has come to medicine late,but“it is now undergoing a boom in popularity,”said Dr.Thomas C.Chalmers,a distinguished physician of the Department of Veterans Affairs in Boston and a pioneer in methodology.,The method involves an analysis of previous analyses.It combines the results of a wide range of existing smaller studies and then applies one of several statistical techniques to discover more precisely what is known from previous research.It may also produce a unified result from diverse,apparently contradictory studies.,The technique has already shed new light on the effectiveness of medical therapies.Although it has not,in itself,revolutionized any medical treatment it has helped clear away the confusion caused by studies with scattered and apparently conflicting findings and has strengthen and confirmed findings from traditional clinical trials.,NY Times,8/21/90,临床试验的Meta分析,4,New Method of Analyzing Health,Reference:NIH Proceedings,Methodologic Issues in Overviews,of Randomized Clinical Trials,NIH Conference,May 1986,Statistics in Medicine,Vol 6,No.3,1987,临床试验的Meta分析,5,Reference:NIH ProceedingsMeth,What is the Purpose?,a.Testing for a treatment effect(rejecting the null hypothesis),b.Evaluating a safety issue(rare events),c.Estimating size of treatment effect in subgroups,d.Design of new studies,e.Develop practice guidelines,临床试验的Meta分析,6,What is the Purpose?a.Testing,Ideal Meta Analysis,is,Randomized Multi-center Control Trial,Same protocol,Same treatment,Same type of subjects,Same outcome measure,临床试验的Meta分析,7,临床试验的Meta分析7,Issues in Meta Analysis,Differences Across Studies in:,a.Treatment,b.Control Group/Population,c.Time Span(Disease,Background Therapy),d.Outcome Measures,Publication Bias,Completeness/Quality of Data,Access to Data,临床试验的Meta分析,8,Issues in Meta AnalysisDiffere,What Studies Should Be Included?,All existing studies,All published studies,Non-flawed trials,Other selection criteria,临床试验的Meta分析,9,What Studies Should Be Include,Meta-Analysis:When?(1),Retrospective,Analyses,Test Treatment Effect When:,Definitive answer not yet available,No more studies likely,Need to salvage available results,Develop Practice Guidelines,Design New Studies,临床试验的Meta分析,10,Meta-Analysis:When?(1)Retro,Meta-Analysis:When?(2),Prospective,Analyses,Not recommended,Better to design in advance proper multi-center trial(s),临床试验的Meta分析,11,Meta-Analysis:When?(2)Prospe,Meta-Analysis,Methodology Not New,Combining p-values,Fisher(1948),Analysis of Variance,Fisher(1938),Combining 2x2 Tables,Mantel-Haenszel(1959),Cochran(1954),临床试验的Meta分析,12,Meta-AnalysisMethodology Not N,Odds Ratio,more explicitly,OR=ad/bc,T,C,S,a,b,a+b,F,c,d,c+d,a+c,b+d,临床试验的Meta分析,13,Odds Ratiomore explicitlyOR=,Methods of Meta-Analysis,Collapsing can be misleading if there is,qualitative,interaction.,1.0 Collapse Data,RCT-1,T,C,S,15,5,F,85,95,OR=3.35,RCT-2,T,C,S,5,15,F,95,85,OR=0.30,Collapsed,T,C,20,20,180,180,OR=1.0,临床试验的Meta分析,14,Methods of Meta-AnalysisCollap,2.Graphical,See Figure,95%CI for each study,(ad/bc)exp 1.96 (1/a+1/b+1/c+1/d),Methods of Meta Analysis,临床试验的Meta分析,15,2.GraphicalMethods of Meta An,Apparent effects of fibrinolytic treatment on morality in the randomised trials of IV treatment of acute myocardial infarction.,Stat in Med,7:890:1988.,临床试验的Meta分析,16,Apparent