临床试验Meta分析

• Develop Practice Guidelines
• Design New Studies
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Meta-Analysis: When? (2)
Prospective Analyses • Not recommended • Better to design in advance
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Figure 2
Odds Ratios and 95% Confidence Limits for Various Studies and a Pooled Estimate
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New Method of Analyzing Health Data Stirs Debate by Lawrence K. Altman
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Issues in Meta Analysis
• Differences Across Studies in: a. Treatment b. Control Group/Population c. Time Span (Disease, Background Therapy) d. Outcome Measures
Statistics in Medicine Vol 6, No. 3, 1987
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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
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.
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Comparison of meta-analysis of 12 RCTs of i.v.mixed drugs (double-blind) with i.v. metoprolol (double-blind) and i.v. atenlol (open study). Stat in Med 6(3): 320, 1987.
clinical trials.
NY Times 8/21/90
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Reference: NIH Proceedings
Methodologic Issues in Overviews of Randomized Clinical Trials
NIH Conference May 1986
Statistics 542
Introduction to Clinical Trials
Meta Analysis
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Meta-Analysis
Alternatives?
Occasionally
Complementary? Yes
Meta-Analysis
• Combination of similar studies using similar subjects and similar treatments and similar outcomes
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.
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Comparison of meta-analysis of 7 small RCTs of phenobarbital in the treatment of neonatal intra-cranial haemmorrhage with one large co-operative study (3 institutions). Endpoints are total infants with haemmorrhage and totals with severe haemorrhage (Grades III-IV) only. Stat in Med 6(3): 321, 1987.
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.
– Mantel-Haenszel (1959) – Cochran (1954)
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OR = ad/bc
Odds Ratio
T
C
Sa
b a+b
Fc
d c+d
a+c b+d
more explicitly
a /(a c)
OR

c /(a c) b /(b d)

a/c b/d
helped clear away the confusion caused by studies with
scattered and apparently conflicting findings and has
strengthen and confirmed findings from traditional
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
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.
• Publication Bias • Completeness/Quality of Data • Access to Data
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What Studies Should Be Included?
• All existing studies • All published studies • "Non-flawed" trials • Other selection criteria
(ad / bc) exp { ± 1.96 (1/a + 1/b + 1/c + 1/d) }
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Apparent effects of fibrinolytic treatment on morality in the randomised trials of IV treatment of acute myocardial infarction. Stat in Med 7:890: 1988.
subgroups d. Design of new studies e. Develop practice guidelines
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Ideal Meta Analysis is
Randomized Multi-center Control Trial
• Same protocol • Same treatment • Same type of subjects • Same outcome measure
OR = 1.0
Collapsing can be misleading if there is qualitative interaction.
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Methods of Meta Analysis
2. Graphical • See Figure • 95% CI for each study
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Comparison of meta-analysis of mortality in 11 RCTs and reinfarction rates in 10 RCTs of i.v. streptokinase with large co-operative study (GISSI). Stat in Med 6(3): 320, 1987.

ad bc
d /(b d)
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Methods of Meta-Analysis
1.0 Collapse Data
RCT-1 TC
S 15 5 F 85 95
OR = 3.35
RCT-2 TC
S 5 15 F 95 85
OR = 0.30
Collapsed
T百度文库
C
20
20
180 180
proper multi-center trial(s)
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Meta-Analysis
Methodology Not New
• Combining p-values, Fisher (1948)
• Analysis of Variance, Fisher (1938)
• Combining 2x2 Tables
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Meta-Analysis: When? (1)
Retrospective Analyses
• Test Treatment Effect When:
– Definitive answer not yet available – No more studies likely – Need to salvage available results